The Non-Executive Chairman of Mesoblast Limited. I'm joining you today from Arizona in the United States, and it's just past the appointed time. As we have a quorum present, it is my pleasure to now declare the 2021 Annual General Meeting of Mesoblast Limited formally open, and to welcome you on behalf of my fellow directors. We're very pleased you have joined us today, and we welcome the opportunity to update you in person regarding the achievements of our company in the last year. With the ongoing COVID-19 pandemic and associated restrictions, we're holding this meeting virtually. While this virtual format may be familiar for some shareholders, I acknowledge that it may be less so for others. However, I assure you that you will have a similar opportunity to participate today as you would at a physical meeting.
This includes being able to ask questions through the online platform and through a dedicated phone line, and vote using an electronic voting card. I'll discuss these processes a little later. I also encourage you to download the online portal guide from Mesoblast website if you've not already done so. If in the unfortunate situation we experience technical issues that impact the meeting, I'll make an assessment of the circumstances and then communicate further with you. If the technical issues are isolated to my location, then I've nominated Don O'Dwyer to assume the chair and continue the meeting. In the event we take steps to adjourn the meeting, we will make an announcement to the ASX with all relevant details. To minimize the risk of any technical failure, the meeting will be conducted in an audio format though Dr. Silviu Itescu will be on video for his presentation.
First, I'd like to introduce my fellow directors, Dr. Silviu Itescu, Chief Executive, who is joining us from Melbourne. Mr. Donal O'Dwyer, Non-Executive Director and Chair of the Nomination and Remuneration Committee, who's joining us from Sydney. Mr. Michael Spooner, Non-Executive Director and Chair of the Audit and Risk Committee, who is joining us from Brisbane. Mr. Philip Pacina, Non-Executive Director, who is joining us from Virginia in the United States. In addition, we have three other non-executive directors who, unfortunately, due to time differences, were unable to join us today. Mr. Bill Burns, Ms. Shawn Tomasello, and Dr. Eric Rose. I'm also pleased to say we have a number of key executives joining us to answer questions. Ms. Dagmar Rosa-Bjorkeson, Chief Operating Officer. Dr. Fred Grossman, Chief Medical Officer. Ms. Geraldine Storton, Head of Regulatory Affairs and Quality Management. Mr. Andrew Chaponnell, Interim Chief Financial Officer.
Also available today is a representative from the company's auditors, PwC, Mr. Sam Lobley, our General Counsel, Mr. Peter Howard, as well as Mr. John Steven from our solicitors, MinterEllison. Finally, also joining us is Ms. Neva Chikamor, our Company Secretary. She'll be reading out the questions that are submitted online by shareholders today. I'd like to now outline the order of business that will be undertaken today. First, I'll go through some procedural matters on voting and asking questions at the meeting. Following that, I'll say a few words about the past year for Mesoblast. Dr. Silviu Itescu will then provide an update on the operational and strategic developments of the business. Following his presentation, I will proceed with the more formal aspects of the meeting as outlined in the notice of meeting.
Finally, I'll hand over to Dr. Itescu to answer, time permitting, general shareholder questions following the completion of the formal business of the meeting. Let's move now to the voting and questions procedures. Voting on all resolutions today will be conducted by way of a poll. Shareholders will have the option of casting their vote before the meeting or appointing a proxy, attorney, or corporate representative to do so on their behalf. If you haven't done so, you can vote at today's meeting online anytime during the meeting, starting from now, using the electronic voting card you should receive after clicking Get a Voting Card button. Voting will close shortly after the end of the meeting. We received some questions in the lead up to the AGM, which we will address when we go through the formal business of the meeting.
Shareholders can submit written questions during the meeting by clicking on the Ask a Question button and then typing and submitting their question. I encourage you to submit your questions as soon as possible, and we will address as many of these as we can during the course of today's meeting. If we receive multiple questions that are similar, we'll combine them into one or choose to answer the broadest question, which should cover the others. If you have difficulties using the platform, please check the online portal guide on Mesoblast's website. Shareholders are able to ask questions by phone if they have preregistered and obtained their unique pin. Instructions on how to do so are displayed on the screen.
To assure all shareholders have the opportunity to ask their questions, we request that you limit yourself to one question and then rejoin the queue if you have further questions. At this point, I'd like to offer my chairman's report. 2021 has been a rollercoaster year for the world and a challenging year for both meaningful progress as well as some setbacks from Mesoblast. We've gone from the elation of seeing an FDA-compiled panel of experts vote in favor of our lead product, a potentially company-transforming partnership with global pharma and some very impressive clinical results, to delays in our foundational submissions to the U.S. regulatory authority.
Despite these challenges, our core therapies, remestemcel-L and rexlemestrocel-L, have continued to deliver results that demonstrate their life-saving potential in addressing four complex medical disorders, graft-versus-host disease, acute respiratory distress syndrome, advanced heart failure, and chronic lower back pain. Over the past 12 months, nothing has given me greater pride than seeing the progress of our remestemcel-L therapy in young children suffering from steroid-refractory acute graft-versus-host disease, or commonly referred to as GVHD. This is surely one of the cruelest diseases striking and often taking the lives of innocent young children who have already undergone the ordeal of a bone marrow transplant. Following a presentation of study results to the FDA's advisory panel last year, and the panel then voting overwhelmingly in favor that the data supported the efficacy of our GVHD therapy, we were very disappointed that an approval did not materialize.
However, we've regrouped, and after addressing the outstanding items that the FDA requested, we're confident that our collegial collaboration could lead to a resubmission of our current biologic license application. The additional investments we've made with respect to remestemcel-L will also support commencement of a second phase III trial for acute respiratory distress syndrome, or ARDS, associated with COVID-19, a deadly combination of inflammatory reactions that has claimed so many lives during this pandemic. Promising results from our first ARDS trial, together with a recent constructive meeting with the FDA, paves the way for a highly anticipated follow-up study and a pathway to potential emergency use authorization for patients with the highest risk of mortality.
Our second cell therapy, rexlemestrocel-L, has also received a recent boost with its presentation at the American Heart Association's 2021 scientific sessions, where the latest results were outlined in a five-year phase III trial involving 565 patients, the largest ever trial of a cell therapy for heart disease. Mesoblast is excited by these results, which are due to be published by a major medical journal and will inform the progress of our other major submission before the FDA. As a board, we're focused on governance responsibilities as well as our need to improve diversity on the board in order to benefit from a wider perspective that having a diverse membership brings. We're committed to enhancing gender diversity, in particular, as we bring on new directors.
Our board membership has transitioned in recent years as Mesoblast heads toward the potential approval of its first product, with new appointments being Ms. Shawn Tomasello, Mr. Philip Pacina, and myself. We've all brought diverse experiences to the board. Sean with more than 30 years commercial and transactional experience in the pharmaceutical and biotech industries, Philip with more than 35 years of experience with corporate strategy, capital markets, and business development, and then myself with more than four decades of healthcare leadership experience as a payer and provider executive. In addition, I have served as chairman of the Institute for Diversity in Health Management and currently serve as an advisor to the National Association of Corporate Directors Center for Inclusive Governance.
With the new appointments well settled into the board, we are committed to a program of board renewal with two of our long-standing Australian directors standing down in the next 6 to 12 months, and a search having commenced for successor Australian directors. The next 12 months will be pivotal period in the evolution of our company as a number of regulatory processes draw toward a close with the assiduous support of our clinical staff. I would like to take this opportunity to thank all of the remarkable researchers and healthcare professionals who made this possible, as well as the diverse investment community who continue to show faith in our work. I would particularly like to thank our Chief Executive Officer, Dr. Silviu Itescu, our management team, and our employees for their resilience, resourcefulness, and incredible dedication over the past 12 months.
It's been a tough and unprecedented period, particularly for the world's clinical community. At Mesoblast, we continue to be awed by the deep commitment and compassion that our healthcare professionals and scientists have demonstrated throughout this pandemic. I'm proud to have seen these same qualities reflected across all levels of the team as we continue to navigate the hurdles, bringing our lead therapies to the millions of people whose lives could be improved by them. I would like to now hand over to our Chief Executive, Dr. Silviu Itescu, who will elaborate on Mesoblast's corporate progress.
Thank you very much, Joe, and welcome to everybody on this call. If we could go to slide 12, please. We understand the mechanism of action of our platform technology. Our stromal cells have, on their surface, a number of receptors that are able to be activated when the cells find themselves in the middle of the inflammatory process, a severe cytokine storm. When they're activated through these receptors, they release a multitude of factors that are also well-defined that turn off multiple arms of the immune system, and that forms the basis of the target diseases that we go after. Next slide, please. This is a snapshot of our maturing pipeline. We have two product candidates, remestemcel-L and rexlemestrocel-L, and each has its own particular indications and strategic partners.
Remestemcel-L is being developed for acute graft-versus-host disease in children and subsequently in adults, as well as acute respiratory distress syndrome, initially for COVID-19, and beyond that, for other viral infections and other causes of severe inflammation in the lung. In addition, we're developing the product for refractory inflammatory bowel disease. Rexlemestrocel-L is being developed for localized delivery into the inflammatory heart in patients with advanced heart failure and in the inflammatory intervertebral disc for patients with chronic low back pain. To the right, you can see our various commercial partners who are either our partners globally for certain programs and indications or regionally for other developments in Europe, China, and Japan. Next slide, please. The financial highlights that we presented most recently are identified on this slide, 14.
We successfully entered into a refinancing and expansion of our senior debt facility with Oaktree Capital Management. The new $90 million five-year secured facility has a three-year interest-only period, after which time 40% of the principal will amortize over two years, and a final payment will be due no later than November 2026. Our cash on hand at the end of the last quarter was $116 million, and importantly, sales of TEMCELL, our mesenchymal stromal cell product that is being sold in Japan by our licensee JCR for the treatment of acute graft-versus-host disease, has demonstrated a steady growth trajectory after the plant capacity was expanded to meet continued and growing demand.
The revenue from TEMCELL royalties increased by 10% from the prior year period overall to $7.2 million in the year ended June 30. In the most recent quarter, ended September 30, revenue from TEMCELL royalties was $2.4 million, an increase of 22% on the previous quarter and of 90% on the comparative quarter for last year. We are pleased by these numbers. In the most recent quarter, net operating cash usage was down $8.6 million from the comparative quarter to $19.6 million. Approximately 50% of the net operating cash usage was to support the regulatory pathway to approval, manufacturing scale-up, and lifecycle management of our lead product candidate, remestemcel-L, for the GVHD and COVID-19 indications.
Now let's move on to the lead diseases for which remestemcel-L is being developed, acute graft-versus-host disease and then acute respiratory distress syndrome. If we could go to slide number 16, please. Acute graft-versus-host disease is a serious and fatal complication of an allogeneic bone marrow transplant. When an individual gets treated for cancer, and is often cured for the underlying cancer, there is a bone marrow transplant that is provided to rebuild and replenish the bone marrow. During the conditioning regimen for this bone marrow transplant, tissue damage occurs. The bone marrow transplant then recognizes the recipient tissues as foreign, and the immune cells of the bone marrow from the donor attack the gut, the liver, and other organs by releasing various cytokines, a so-called cytokine storm, that is potentially fatal. Next slide, please.
Children with steroid-refractory acute graft-versus-host disease are at particularly high risk of treatment failure and death. More than 2,000 allogeneic bone marrow transplants occur annually in the U.S. alone in children, and despite adequate prophylaxis, more than 50% will develop acute graft-versus-host disease. Half of these will be refractory to steroids, and for these children, unfortunately, under the age of 12, there are no approved treatments. The disease affects frequently the gut and the liver, and when it affects these organs, the mortality is as high as 90%. This is after the fact that they've been adequately treated and cured of the underlying leukemia. Next slide, please.
We've presented data from three distinct studies that have demonstrated that remestemcel-L used in children with steroid-refractory acute graft-versus-host disease results in significant clinical outcomes in terms of day 28 response and day 100 and day 180 survival. As shown on this slide in yellow across these three different studies, the day 28 response was between 64%-69%. In contrast, in control groups of children, either within a placebo-controlled study or the overall day 28 response is as low as 38%-43%. In terms of survival, the three trials where remestemcel-L was used demonstrated an overall survival through day 100. Slide is the survival curve in a single center study of children with acute graft-versus-host disease and then refractory to steroids, 370 children.
As you can see in red that at six months, survival in these children, despite maximal alternative therapies, by 24 months falls to a dismal 35%. They demonstrate only one in 10 having a responder at day 28 to various therapies. In contrast, those treated with remestemcel-L had a 67% responder outcome within 28 days, and this was significant. On the right-hand side, you see survival outcomes matched by high-risk MAP criteria. Again, as you can see, the children from the MAGIC cohort, only one out of 10 was alive at six months, compared with seven out of 11 treated with remestemcel-L alive at 6six months. 64% versus 10%, P = 0.01.
In particular, where remestemcel-L is making a real difference is in those children who are at highest risk of death, where inflammation is greatest, and where alternative therapies just do not work. If we go to the next slide, 22. Where are we with respect to the regulatory and commercial pathway to approval for remestemcel-L in children with steroid-refractory GVHD? The data I've just shown you provide further support for the proposed anti-inflammatory mechanism of action of remestemcel-L and its immunomodulatory activity in patients with steroid-refractory acute GVHD, resulting in clearly improved survival outcomes. Mesoblast has an upcoming scheduled meeting with the FDA, the Office of Tissues and Advanced Therapies, OTAT, to address the appropriateness of our potency assays as they relate to remestemcel-L's proposed anti-inflammatory mechanism of action, including biomarkers and including survival outcomes.
These discussions form part of the ongoing process that has been ongoing since our disappointing CRL last year to resolve the outstanding items with the goal of resubmission of the BLA and ultimately achieving approval of remestemcel in treatment of steroid-refractory GVHD in these very desperate children who need this therapy. Let's move on to the next slide. In the past two years, it has become evident that remestemcel has the ability to make a major impact in the dismal outcome of acute respiratory distress syndrome, initially due to COVID-19, but likely due to other indications as well, other causes as well. COVID-19 is a well-established respiratory virus with a high mortality due to severe inflammation of the lungs called ARDS. ARDS is caused by cytokine storm in the lungs in patients affected with this disease and is the primary cause of death.
The extensive safety data of remestemcel-L and its understood anti-inflammatory effects and mode of action in GVHD makes a compelling rationale for evaluating remestemcel-L in COVID-ARDS. Moreover, the fact that following intravenous delivery, remestemcel-L homes selectively to the lungs, makes inflammatory lung disease an ideal target for this therapy. Let's have a look at where we are with respect to clinical outcomes and the pathway to potential EUA, Emergency Use Authorization. I think what's also important is to understand, in slide 24, the evolving pandemic and what is now understood as to the relationship between the virus and the host immune response. As you can see in the bottom left figure, a normal immune response to COVID-19 requires having a healthy T cell arm that is able to handle the virus and eliminate it rapidly.
Unfortunately, as people get older, the T cell arm of the immune response becomes defective. The virus is not cleared rapidly. In fact, viral load continues to increase, as seen on the slide to the right. All the way to the right, what that results in is more severe disease, greater viral load, greater inflammation, and ultimately higher mortality rates, the older the patient. Slide 25 summarizes the pathway we have taken to bring remestemcel-L into this disease opportunity. Initially, we evaluated under an emergency IND in ventilator-dependent patients at Mount Sinai Hospital. 11 patients, all of whom ten of whom were under the age of 65 with moderate severe ARDS on ventilators. In these first 11 patients, we saw very striking results. 82% successfully came off ventilators within a median of 10 days and were discharged.
That experience informed how we moved forward with our partners at the National Institutes of Health into a randomized controlled trial that was targeting up to 300 patients, and ultimately enrolled 222 patients. The median age during this trial changed quite distinctly from initially 59 in the first half of the trial to 67, a decade older in the second half. This was primarily because many experimental therapies were trialed and now proven to have failed, but offered to patients well before they were offered to enter into our study. Over time, the patient population turned out to be sicker, older and more end-stage. We evaluated the results by age, as was pre-specified in the overall study. Next slide, please.
As I've highlighted, age was a primary risk factor for mortality in this study, and in the controls, as you can see in the pre-specified cutoffs of less than or older than 65, there was a distinct difference in survival, such that the older patients had a 70% mortality, younger patients still had a 42% mortality. Now, a 42% death rate over a two-month period is still a terrible outcome for young people who are being infected more and more frequently with this terrible disease. Next slide, please. The highlights of this study are on the very next slide 27. As you can see here, in the younger patients who now make up about two-thirds of hospitalized and ICU-based patients, and where the virus is infecting more and more frequently.
In these patients under the age of 65, we saw a 46% reduction in mortality through 60 days, where the control population had a 42% death rate, and the treated patients with just two doses of our cells given five days apart had a 26% overall mortality. As you can see on the right-hand side, when we looked at the key secondary endpoint of overall improvement in respiratory function, we see that a significant increase was seen at every time point from day 14, 21, and day 30 in red in those patients who received remestemcel-L 2 doses compared to those who received placebo. This indicates that these patients improved by at least one major category from severe to moderate, from moderate to mild, or to no ARDS residual at all.
This was mirrored in addition by a variety of other key secondary endpoints, and now as we see additional biomarker data support a mechanism of action that explains why we see this survival benefit through at least 60 and 90 days. Next slide. Now, the other key finding in this study was the synergy between our cells and the only drug approved in patients on ventilators, which is dexamethasone. What you see here amongst the dexamethasone-treated patients, which again was a drug that was instituted midway through this overall trial. You can see that in blue on the left-hand side, dexamethasone-treated control patients had a 48% overall mortality rather, compared to only a 14% mortality in red in those patients who received both dexamethasone and two doses of our cells.
This is almost an 80% reduction in mortality, which is a very dramatic effect and is reflected on the right-hand side in the synergy in each of the key secondary endpoints, including overall improvement in respiratory function at every time point tested. This is again seen and supported by various biomarker data that continue to explain the mechanism of action and why the cells should be synergistic together with dexamethasone and other corticosteroids. If we can go to the next slide, please. What have we learned, and what is the regulatory pathway to a potential emergency use authorization for remestemcel-L in COVID-19 ARDS? We met with the FDA in regard to potential EUA in the treatment of ventilator-dependent patients with moderate to severe ARDS very recently.
The FDA advised that on the basis of the data that we've demonstrated, if a second study confirmed the observation and was statistically positive, it could provide a data set to support an emergency use authorization. The FDA additionally indicated that potency assays need to be established and agreed prior to commencement of this trial, and that such potency assays that we're reviewing with the FDA for GVHD would likely be appropriate for COVID, as would the entire, CMC data set in the BLA for GVHD. In other words, they were able to reference the CMC, the manufacturing and the potency data, that are being presented to GVHD currently for COVID ARDS. We plan to move forward with an additional phase III trial, with the next step being to agree with the FDA on both the final protocol and the potency assay for the product.
This becomes an even more urgent next step given the recent findings that we're all familiar with around the new variant of concern and its likelihood of more rapid spread globally. Now let's move on to some of the other indications for rexlemestrocel-L in particular, and the very exciting data that we've just heard presented at the American Heart Association. First, on our back pain data. Rexlemestrocel-L is providing the potential for a new paradigm in the treatment of inflammatory low back pain due to degenerative disc disease, which continues to be a major unmet need and continues to be the number one cause of prescription opioid usage across the U.S. and other Western countries.
The results that were presented earlier support the idea that this single injection into the inflammatory disk may give us durable and long-term reduction in pain in a way that is just not achievable with alternative therapies such as opioids. The study that has been presented demonstrated significant pain reduction across all patients in the study, 391, at 12 and at 24 months, with no safety concerns. Moreover, similar results were shown in patients who were on opioids at baseline, and those accounted for about 40% of patients. Through 24 months, what we saw in this group of patients was as much as 40% reduction in opioid usage. The conclusion is that rexlemestrocel-L may provide a safe, durable, and potentially effective opioid-sparing therapy for patients with chronic inflammatory back pain due to this common disease.
The greatest benefits are seen when the cells are administered earlier in the disease process, which is a phenomenon that we're seeing across each of the indications before there is entrenched fibrosis and irreversible disease. We will update the market in due course as we get feedback from the FDA on the pathway for the next program. Now let's move on to heart failure. Chronic heart failure is a disease that remains the leading cause of death in the United States, affecting more than 6.5 million patients in the U.S. alone, and growing as the population is aging. Chronic heart failure is an inflammatory disease and has a high mortality, and at least 75% will die after initial hospitalization within the subsequent five years. This is a disease with a mortality rate that is as high as many cancers.
In heart failure, these drugs primarily target neurohormonal complications and volume difference. If we go to the next slide 34. This is a schematic of the complex mechanism of action of rexlemestrocel-L. Essentially, if you can focus on in the heart, the green is the inflammatory cell called the macrophage, which is activated. It secretes various inflammatory cytokines, including TNF, IL-1, and IL-6, and that causes progressive destruction of the heart muscle and high risk for recurrent heart attacks and other vascular complications. When we put rexlemestrocel-L into the inflamed myocardium, it is able to be activated by these cytokines and then, as I've said earlier, releases anti-inflammatory factors that turn off the inflammatory immune cell.
That, we believe, results in improvement in protection of the heart muscle against death, improvement in the vascular density in the myocardium, and protection of the large vasculature against occlusions like heart attacks. Next slide, please. Slide 35 is a summary of what was presented a week ago at the American Heart Association annual meeting. Data from the randomized controlled phase III trial in 565 patients with New York Heart Association Class 2 and Class 3 low ejection fraction patients were presented as a peer-reviewed, late-breaking presentation. It was presented by the trial's co-principal investigator, Dr. Emerson Perin, who is the medical director of the Texas Heart Institute and clinical professor at Baylor College of Medicine.
The newly presented data from this landmark study showed a significant relationship between the presence of systemic inflammation as quantified by biomarkers such as CRP and treatment benefit in high-risk patients on cardiovascular mortality, heart attacks, and strokes. If we can go to slide 36. The primary endpoint was not met, as we've mentioned earlier, and that's primarily because the primary endpoint already demonstrates a reduction of symptomatic hospitalization due to volume-related overload that is adequately treated by a variety of drugs that are out there today. Therefore, rexlemestrocel-L did not add benefit on top of the existing drugs on these symptomatic outcomes. Slide 37. However, this is where we see a divergence from existing therapies.
On top of maximal standard of care, a single intervention with rexlemestrocel-L resulted in significant reduction over as long as four-five years of follow-up in all treated patients and in Class II and III patients separately on the incidence of non-fatal heart attacks or strokes. These reductions were of the order of 65%, quite a large reduction in risk incidence of these severe outcomes. If we can go to the next slide, please. Slide 38.
We also see that in particularly the Class II patients who are early in their stage of progression, a very significant reduction in cardiovascular death rate of the order of 57% on the left-hand panel, and particularly of the order of 80% in the middle panel when those Class II patients were selected on the basis of the presence of inflammation as measured by CRP. If we can go to the next slide, please. Slide 39. This slide starts to look at the composite endpoint of what we call the three-point Major Adverse Cardiac Event, or MACE.
This is an endpoint that the FDA has used multiple times to approve drugs in patients with high risk of cardiovascular outcomes, adverse outcomes, including in patients with diabetes, and a number of the drugs that are now approved, both in diabetic patients and in heart failure patients, have been approved on the basis of this exact endpoint. As you can see on the left-hand panel here, across all 537 treated patients, a single intervention of rexlemestrocel-L reduced the three-point MACE significantly by 33% over a long period of follow-up.
Most importantly, in the middle panel, you can see that when we select patients on the presence of the biomarker CRP, a simple, well-established, validated biomarker that physicians in their practice, in their offices measure, you can see that this specifically identifies the highest-risk patients and those patients most likely to respond to a single intervention of rexlemestrocel-L. Here we see an overall 45% reduction in the risk of a three-point MACE over a four-five-year follow-up period. The separation occurs as early as year one. This is the endpoint that we are most excited about, that we'll talk a lot more with the FDA as we continue our interactions.
The conclusions of this study are that transendocardial delivery, the next slide, 40 of 150 million allogeneic MPCs was safe, did not elicit any clinically meaningful immune-related outcomes that were adverse. Over a mean follow-up period of 30 months, the longest such study of cell therapy in these patients with heart failure, chronic advanced heart failure. A single intervention with rexlemestrocel-L added on top of maximal approved standard of care, significantly reduced non-fatal heart attacks, non-fatal strokes across all Class 2 and 3 patients, cardiac death, particularly in Class 2 patients, and the composite of cardiac death or non-fatal MI or stroke across all patients, 537 treated patients. Most evident, though, was seen in those patients with evidence systemically of inflammation.
I think on that note, I might stop, and I'll hand it back to our Chairman to conclude the more formal part of this AGM. Thank you.
Overview on the significant progress our business has made over this year, and the exciting milestones coming up for this 2022 fiscal year. We're now going to move to the formal business of this meeting. I can confirm the notice of meeting was sent to all registered members, the company directors, and the company's auditors in accordance with the company's constitution and the Corporations Act. In addition, the copy of the notice of meetings has been lodged with the Australian Securities Exchange. I will take the notice of meeting dated 29 October 2021 as being read. Mesoblast's share registry provider, Link Market Services, will conduct the voting by way of poll, and Mr. Jim Kampouropoulos of Link will act as Returning Officer. I remind you that voting has opened and will close at the end of the meeting.
Votes will be counted after the end of the meeting and results published on the ASX and Mesoblast's website. Before a vote is taken, I will inform the meeting of how many proxy votes have been received. As indicated in the notice of meeting, I will be voting all undirected proxies given to the chair of the meeting in favor of all resolutions considered at this meeting. I'll now move each of the resolutions separately, and we will provide an opportunity for questions on each one. Shareholder questions on general business will be answered in a Q&A session immediately after the resolutions. The company's annual report includes the financial statements and directors' declaration, the directors' report, and the auditors' report for the year ended June 30, 2021. I will take these reports as read.
While no resolution is required in relation to the financial statements and reports, shareholders, their corporate representatives, attorneys, or their proxies are entitled today to ask questions of the directors or the auditor in relation to these reports. I ask that any questions concerning the remuneration report be raised at the next agenda item. Questions may also be asked of the auditor concerning the conduct of the audit, the preparation and content of the auditor's report, accounting policies adopted by the company, and the independence of the auditor in carrying out the audit. I now invite shareholders to submit any questions on this item of business. I will pause to receive any questions. Neva, are there questions with regard to this item of business?
Joe, there's been no questions received on this item.
Thank you. Are there questions from telephone participants?
Thank you. There are no questions on the phone line.
Thank you. We will move to our next item of business. The board submits its 2021 remuneration report to shareholders for your consideration and approval. The Corporations Act requires companies to put to shareholders a non-binding vote to enable shareholders to voice their opinion on matters included. I will now pause to give shareholders the opportunity to submit any questions online. Neva, are there questions with regard to this item of business?
Joe, we've received one question on this item of business. The question is from Stuart Burn, representing the Australian Shareholders' Association. The question is, Chairman, with regards to the CEO's remuneration and specifically his LTI component, it does not appear to be any TSR hurdle in this component. Can the company please comment on how they perceive his remuneration is linked to shareholder returns?
Yes. Thank you for the question. I believe it's best answered by the chair of our nomination and remuneration committee, Mr. O'Dwyer. Donal, please r espond.
Yeah. Thanks, Mr. Chair. Also thanks, Stuart and the Australian Shareholders Association for the question. Look, we've had this conversation with Stuart and his colleagues on a number of occasions. Whilst we acknowledge that TSR is a hurdle that's routinely used within Australian companies in relation to vesting hurdles for options, we do not think it's appropriate for Mesoblast. The reason is, first of all, we're very different to the other companies on the Australian Securities Exchange. We are still in the process of developing to be commercialized to commercialization. Because of that, we can have many cases of pretty high volatility in our share prices that really we don't think therefore using TSR is an appropriate hurdle.
What we do believe is important is that the company identifies a set of meaningful milestones on its route to a significant event that will unlock shareholder value, be it either a product approval or a partnership with another organization. We believe that the appropriate hurdles that we should trigger the investing of any LTI instrument are the achievement of such milestones. That's the approach that we as a company have been pursuing for several years, and we believe it's the appropriate one for us at this stage. That concludes the question. Thank you. Or my answer to the question.
Very good.
Back to you, Mr. Chair.
Very, very good. Thank you for the response. Neva, I pause for a moment to ask if there are any other questions that have been communicated to you.
Joe, we've not received any other questions on this item.
Very good. Are there questions from the telephone participants?
Thank you. There are no questions on the phone line.
Great. Thank you very much. Proxy votes received for this resolution are displayed on the screen. I now propose resolution two as set out in the notice of meeting, and put the resolution to a vote by poll. Will you please cast your vote? I will pause to allow you to cast your vote, and then we will move on to the next resolution. Very good. We'll now move to discussion of resolution three, which involves the election of Mr. Philip Pacina as director. He was appointed to the board as a director on March 29, 2021. He is eligible and wishes to offer himself for election by shareholders. The board recommends that shareholders vote in favor of the election of Mr. Pacina. He did not participate in the board resolution relating to his candidacy.
I will now pause to give shareholders the opportunity to submit any questions online. Neva, are there any questions with regard to resolution number three?
Joe, no questions have been received on this item.
Thank you. Are there questions from telephone participants?
Thank you. There are no questions on the phone line.
Again, thank you very much. Proxy votes received for this resolution are displayed on the screen. I now propose resolution three, as set out in the notice of meeting regarding the election of Mr. Pacina and put the resolution to a vote by poll. I will pause to allow you to cast your votes. We'll now move to discussion of resolution four, which involves the re-election of each of Mr. Michael Spooner, myself, Mr. Joseph Swedish, and Ms. Shawn Tomasello. The board recommends that shareholders vote in favor of the re-election of each of these candidates. Each candidate has not participated in the board resolution relating to their own candidacy. As set out in the notice of meeting, the directors remain committed to ensuring continued change and board composition in line with good governance practices for director tenure and diversity.
Accordingly, it is proposed that each of Mr. Michael Spooner, if re-elected, and Mr. Donal O'Dwyer, as long-standing Australian non-executive directors, will retire from the board over the coming six-12 months. A search for appropriate Australian successors has commenced. I thank both Michael and Donal for their enormous contributions to Mesoblast over many years of service. I will now deal with each resolution separately. Resolution 4A deals with the re-election of Mr. Michael Spooner. Mr. Spooner will retire by rotation in accordance with the company's constitution. He is eligible and wishes to offer himself for re-election. I will now pause to give shareholders the opportunity to submit any questions online. Neva, are there questions with regard to resolution 4A?
We have received a question on this resolution. The question is from Stuart Burn, representing the Australian Shareholders' Association. The question is, Chairman, Mr. Spooner has been on the board for 17 years and is not considered by the ASA to be independent. Can you please advise why he is seen to be independent and why he should be re-elected to the board as an independent director?
Mr. Burn, thank you for the question, and let me respond by saying, as previously mentioned, we recognize Mr. Spooner's tenure on the board, and he has agreed to step down in the next six-12 months. Michael is in a transitional period, assisting the company to find an appropriate successor as chair of the Audit and Risk Committee. The board is grateful for his work on the board, particularly with respect to leading the Audit and Risk Committee. With respect to independence, the board considered Michael's tenure and a number of other factors when assessing independence, as outlined in the ASX Corporate Governance Principles and Recommendations. The board did assess that he has not formed associations with management or others that might compromise his ability to fulfill his role as an independent director.
As chair, I have seen Michael exercise independent judgment on matters raised by the board. Again, thank you for the question, and I believe I've responded appropriately regarding the transition as well as his contributions to the board. Neva, are there more questions that may have surfaced regarding online?
No, there are no more questions on this item.
Very, very good. Are there questions from telephone participants?
Thank you. There are no questions on the phone line.
Thank you. Proxy votes received for this resolution are displayed on the screen. I now propose resolution 4A, as set out in the notice of meeting regarding the re-election of Mr. Spooner, and put the resolution to a vote by poll. I will pause to allow you to cast your votes. As the next resolution pertains to my re-election as a director, I will hand this meeting over to.
Stuart for the question, I can assure you that Mr. Swedish is a strong supporter of Mesoblast and in fact has requested to receive shares in lieu of cash payments for his services as a director. Neva, are there any other questions with regard to this resolution?
No further questions have been received.
Are there any questions from telephone participants?
Thank you. There are no questions on the phone line.
Okay. Thank you. Look, prior to our handing back to the chair, I just wanted to note that Joe mentioned that this would be my last annual general meeting participating as a director of Mesoblast. I just wanted to say to all of our shareholders, thank you for your continued support in our great company. I also want you to know that it's been an absolute privilege to serve on your behalf. With that, back to the chair. Thank you.
I can state that proxy votes received for this resolution are displayed on the screen. I will now propose resolution 4B as set out in the notice of meeting regarding the re-election, and put the resolution to a vote by poll. I will pause to allow you to cast your votes. Very good. Thanks, Donal. Again, appreciate your service to the board. It's been remarkable for so many years. Thank you very much. Resolution 4C deals with the re-election of Ms. Shawn Tomasello. Ms. Tomasello will retire by rotation in accordance with the company's constitution. Ms. Tomasello is eligible and wishes to offer herself for re-election. I will now pause to give shareholders the opportunity to submit any questions online. Neva, are there any questions with regard to Resolution 4C?
Thanks, Joe. We have received a question from Stuart Burn representing the Australian Shareholders' Association. Question is, Chairman, Ms. Shawn Tomasello has no shareholding in the company, which shows a lack of faith in the future of MSB. Why should she be reelected to the board of a company she does not seem to support financially?
Again, thank you for the question. Ms. Tomasello, I can underscore, serving with her, observing, is a very strong supporter of Mesoblast and has invested significant time in advising the management team repeatedly as the company gets closer to the potential launch of its first product. Ms. Tomasello has also requested to receive shares in lieu of cash payment for her services as a director. Are there any questions from telephone participants?
Thank you. There are no questions on the phone line.
Proxy votes received for this resolution are displayed on the screen. I now propose resolution 4C as set out in the notice of meeting regarding the re-election of Ms. Tomasello and put the resolution to a vote by poll. I will pause to allow you to cast your votes. We now move to a discussion of resolution five concerning the proposed issue of options, Mr. Philip Pacina relating to his recent appointment as a non-executive director of Mesoblast. I will now pause to give shareholders the opportunity to submit any questions online. Neva, are there questions?
Thanks, Joe. We have received a question from Stuart Burn representing the Australian Shareholders' Association. The question is, Chairman, the issue of shares as part of sign-on agreements is against ASA policy unless unavoidable. Can the chairman please advise why it was necessary to provide a sign-on benefit to Mr. Pacina?
Yes, thank you. Let me try to answer the question with respect to his appointment to the board and the considerations that occurred in doing so. For clarity, we're proposing to issue options to him, not shares. Mesoblast is a biotechnology company, dual listed with Nasdaq, with multiple U.S. and other international directors. Given this, we need to ensure our remuneration framework is relevant to and competitive in multiple jurisdictions. In the U.S., it's expected that for directors to join a biotechnology company board that they be compensated through options rather than large salaries. We have chosen a middle path that meets the expectations of both U.S. and Australian directors. The options granted by Mesoblast to its non-executive directors, including the proposed options to Philip, are issued without any performance or service conditions, so the director's independence and impartiality is not compromised.
Mesoblast has generally granted options to directors at the start of the tenure, which is the case this year with the proposed grant to Philip as an incoming director. The Mesoblast board does not intend to issue or the issue of options to be an annual or regular event for the directors. I will now pause to give shareholders the opportunity to submit any questions telephonically. Are there questions from telephone participants?
Thank you. There are no questions on the phone line.
Thank you. Proxy votes received for this resolution are displayed on the screen. I now propose resolution five as set out in the notice of meeting regarding the issue of options to Mr. Pacina and put the resolution to a vote by poll. I will pause to allow you to cast your votes. We now move to a discussion of resolution six concerning the proposed issuance of options to our Chief Executive Officer, Dr. Silviu Itescu, relating to his remuneration for the 2022 financial year. I invite shareholders to submit any questions on this resolution. Neva, are there questions with respect to resolution number six?
Thanks, Joe. We have received a question from Stuart Burn representing the Australian Shareholders' Association. The question is: Chairman, the vesting conditions for the options for Dr. Silviu Itescu are very vague. Why should shareholders approve the vesting of these options when the vesting conditions, especially for clinical KPIs, have not been set?
I'd like to turn over the question to be answered by our Chairman of the Nomination and Remuneration Committee, Mr. O'Dwyer.
Thanks, Joe. Again, thanks, Stuart for the question. My first answer is that we disagree totally that the milestones and conditions for vesting are vague. In fact, they're very, very specific. We have given an outline of the vesting conditions in the notice of meeting. Given that they're commercially sensitive in nature, we have only provided limited details, but more details will and have been provided in our remuneration report following the achievement of the KPIs. We tend for commercial reasons not to get into too much detail at the beginning, but once the milestones either have been achieved or not achieved, details are given. I should also add that, unlike many other companies that offer LTI instruments in Australia, our instruments are entirely options.
That in itself is a hurdle because unless the actual share price is higher than the issue price, then the options are of zero value to the recipient. We believe that in itself also aligns very much the recipient's incentives with the incentive of shareholders. Back to you, Mr. Chair.
Great. Thank you, Donal. I believe that's responsive to the question. Thank you for the depth. Neva, are there any other questions regarding resolution six?
Thanks, Joe. We've not received any further questions on this resolution.
Thank you. Are there any questions from telephone participants?
Thank you. There are no questions on the phone line.
Thank you very much. Proxy votes received for this resolution are displayed on the screen. I now propose resolution six as set out in the notice of meeting regarding the proposed issue of options to Dr. Itescu and put the resolution to a vote by poll. I will pause to allow you to cast your vote. We next move to a discussion of resolution seven, concerning the renewal of the proportional takeover approval provisions in the company's constitution. This is a special resolution and requires the approval of 75% of the votes cast by shareholders, proxies, attorneys or corporate representatives present and eligible to vote at this meeting. I now invite shareholders to submit any questions on this special resolution. Neva, are there any questions with respect to resolution number seven?
Thanks, Joe. We have not received any questions on this resolution online.
Thank you. Are there any questions from telephone participants?
Thank you. There are no questions on the phone line.
Thank you. Proxy votes received for this special resolution are displayed on the screen. I now propose resolution number seven as set out in the notice of meeting regarding the renewal of the proportional takeover approval provisions in the company's constitution and put the resolution to a vote by poll. I will pause to allow you to cast your vote. Finally, we move to a discussion of resolution eight, the last item on the agenda, concerning the ratification of the issue of securities in our successful institutional placement earlier this year. I invite shareholders to submit any questions on this resolution. Neva, are there any questions with regard to resolution number eight?
Thanks, Joe. We have not received any questions on this resolution online.
Very good. Are there any questions from telephone participants?
Thank you. There are no questions on the phone line.
Thank you. Proxy votes received for this resolution are displayed on the screen. I now propose resolution 8 as set out in the notice of meeting regarding the ratification of the issue of securities and put the resolution to a vote by poll. I will pause to allow you to cast your vote. This brings us to the close of the formal business of the 2021 annual general meeting. In a moment, I will hand over to Silviu for any general questions on the company. Before I do so, I would like to remind you that if you're intending to vote on the formal business of the meeting, you should finalize and submit your votes now. Voting will close shortly after the end of the Q&A session.
As I mentioned earlier, the results of the voting at this annual general meeting will be released to the exchange once the votes have been counted. Thank you for all our shareholders for participating in Mesoblast Annual General Meeting today. We appreciate your ongoing support and loyalty, and look forward to a rewarding year ahead. I will now hand over the meeting to Silviu Itescu for the Q&A session.
Thank you very much, Joe. Neva, can I ask you to read out any questions that we have that are business-related, please?
Thanks, Silviu Itescu. We have received a question from Stuart Burn representing the Australian Shareholders' Association. The question is, at the last two AGMs, you have given an assurance that retail shareholders will be treated equitably with institutional investors in capital raisings. This has not happened. Can you please state that all shareholders will be considered in future capital raisings, preferably using MyoStar?
We are deeply appreciative of the support from retail investors, and our intention always, and certainly in the future, will be to treat retail and institutional investors as equitably as possible. Unfortunately, sometimes that is just not possible due to time constraints and the like. We will nonetheless entirely focus on treating both classes of investors in a similar way.
Silviu, we received another question from Stuart Burn representing the Australian Shareholders' Association. Question is, can you please advise why a decision was made to manufacture remestemcel-L in Singapore prior to approval by the FDA? In retrospect, this appears to have been a poor decision. What are the plans for the current stockpile of remestemcel-L?
In order to receive FDA approval, product must be made in a GMP-compliant facility to FDA specifications, and that's what we've been doing. The whole approach in order to have the FDA be in a position to inspect the manufacturing process and the facility requires inventory to be built in a commercial facility in an FDA-compliant manner. That's what we've put in place. In addition, when we expect and anticipate approval of a first product, we have to have sufficient product available so that it's available immediately to patients in need. That's both from a commercial perspective, from an ethical perspective, and also from a regulatory perspective. All of those are natural and normal deliverables that have been put in place with the anticipation that we will have our first product approved from the FDA-compliant facility in Singapore.
Thanks, Silviu. The next question is also from Stuart Burn representing the Australian Shareholders' Association. We've also received similar questions from a number of shareholders as well. The question is, can you please comment on developments with Novartis and how this alignment will benefit shareholders in the long term?
As a general statement, we continue to evolve our strategy based on our products, and each of our product candidates have their own strategic initiative. For example, graft-versus-host disease product is a relatively small commercial footprint that we intend to build out on our own and focus on commercial delivery. We can talk more about that a little bit later on. Other products have much larger requirements in terms of commercial footprints, and that includes the product for the ARDS indication as well as our cardiovascular indications. For those kind of products, we look to strategic partnerships.
The Novartis partnership is one such partnership that encompasses well beyond clinical development, the focus on the commercial requirements for the large volume indications of inflammatory lung disease, both in the U.S. and outside of the U.S., and that we hope will bring a lot of value to Mesoblast in terms of the strategic alliance.
Thanks, Silviu. The next question follows on. There appears to have been ongoing delay in the Novartis closing. Can you please explain this, and when will the closing occur?
Well, as we have said repeatedly under the terms of the agreement, Novartis requires the sufficient time to evaluate various components of the data that emanated from the 222 patient trial. That included clinical data, biomarker data, manufacturing data, regulatory data, and those, as they come to hand, are being provided and they're being evaluated in a collegial manner between the parties. We hope that we'll be able to close that transaction relatively in short order, and Novartis continues to evaluate the data in a fulsome way.
Thanks, Silviu. The next question is also from Stuart Burn, representing the Australian Shareholders' Association. The question is, Mesoblast continues to show mounting losses, with this expected to continue into the future. This is obviously not a company suited to most retail shareholders unless they are very risk-averse. Can you please advise why this company is listed on the ASX and is not taken private?
I think that shareholders who invest in biotechnology companies need to be well-versed in both the risk but also the reward of biotechnology companies that are developing and bringing products to market with long patent coverage and potential for exclusive revenue streams. Nonetheless, biotechnology by its very essence is a high-risk industry. I think those investors who are looking to invest in biotechnology companies need to understand that there is technology risk, there's clinical risk, and there's regulatory risk, and that is par for the course. I think Mesoblast has experienced those risks. We've outlined them very carefully.
At the same time, it's also evident that we are progressing substantially in a number of major areas where we have a leadership position, where we have strong IP, and where the technology is making major inroads with outcomes that other therapies, including small molecules, including monoclonal antibodies, are just not able to make any difference in. I think the public market is an appropriate place for biotechnology companies to be accessing capital for development. I think it's equally as important for investors to understand that there is inherent risk and in going to these opportunities with their eyes wide open. Nonetheless, the rewards are tremendous for products that ultimately get commercialized.
Thanks, Silviu. The next question relates to our heart failure product. The question is, what are the plans and likely timing for a strategic partner in heart failure?
I think the recent presentation of the American Heart Association makes clear that these results stand alone in terms of delivering outcomes that are just not achievable or certainly not been achieved by the very small molecule drugs that are out there today. The peer-reviewed presentation, late-breaking presentation, highlighted the unique deliverables in this study that Mesoblast achieved. We are in the middle of ongoing discussions with the FDA to get clarity on the pathway to potential approval in the high-risk patient populations using these endpoints and outcomes.
I think it is reasonable to anticipate that following clarity from the FDA, the discussions with potential strategic partners will continue in a way that positions the Mesoblast product in its best possible light and gives shareholders sufficient return to justify an appropriate strategic alliance.
Thanks, Silviu. The next question is, can you provide an update on the current trial of remestemcel-L in inflammatory bowel disease?
Yeah. Thank you. I think this trial is an investigator-initiated program at the Cleveland Clinic by a world-leading investigator in the space. We will be providing additional data in the upcoming quarter, but I think it's important that we work in sync with the investigator. There's been some delay in patient recruitment, of course, during the COVID pandemic, as a result of non-emergent indications and surgical use of facilities being withheld, subject to the ICU use for COVID ARDS patients. I think that has delayed the study, but I think we're very excited to have the investigator put her results out publicly, and we expect that to happen in the coming quarter.
As the investigator presents those data, we will of course make those results available to shareholders.
Thanks, Silviu. The next question is, when is the meeting with ODAC regarding GVHD, and when can we expect to hear about the outcomes of the meeting?
The interactions with the FDA have been significant during the course of this year. We were very disappointed, of course, about a year ago, when, despite the fact that the FDA's own advisory panel, the ODAC panel, voted 9 to 1, almost unanimously, that the product should be approved. Despite that, the FDA review team decided to give us a complete response, primarily requiring an additional clinical trial, but also asking for some clarification on potency assays. Subsequent to that, we have pursued a well-defined process with the FDA leadership in terms of addressing primarily the clinical issues and the current meeting that will be held very shortly with the FDA will focus on our potency assay and its appropriateness with respect to explaining the mechanism of action and how it relates to the clinical outcomes that have been observed.
That will be happening very shortly, and we expect to be updating the market as soon as we have minutes from that meeting.
Thanks, Silviu. The next question is, does Mesoblast continue to supply Ryoncil for compassionate use by children suffering from aGVHD in the USA?
We have on the line our Chief Medical Officer, Dr. Fred Grossman. I would like to ask Dr. Grossman to talk to that specific issue. We have lots and lots of requests. Fred, would you like to address that question, please?
Yes. Thank you, Silviu. Yes, indeed, we continue our compassionate use program. We provide stem cell patients with GVHD, children with GVHD, that meet the same requirements as per our protocol. We certainly are getting requests all the time, and if they meet criteria, we do send cells and work very closely with the physicians who request cells.
I think it's fair to say, Fred, please, chime in here, but I think it's fair to say that the unmet need continues to be very great. Unfortunately, there are only drugs available out there, including the most recently approved drug, that has excessive amount of toxicity in these unfortunate children. We are getting many patients referred to us who are refractory to all existing agents out there, and remembering that there's nothing approved at all for children under 12 due to safety and efficacy concerns. Fred, would you add to that?
Yeah. The requests certainly are coming in for that very reason. As Silviu mentioned, there are no approved treatments for those younger than 12 years of age. Certainly, treating physicians, academics certainly know the data and the survival outcome from our pivotal trial. We get very frequent requests. Even with existing agents, we see that, as mentioned, there's not only toxicity, but efficacy, especially in the more severe cases, is not very high. That leads to-
Thanks, Silviu and Fred. The next question is how secure is our ARDS related patent portfolio? There seems to be a number of others interested in this space from a cell perspective.
Thank you. We have granted patents in the U.S. and in Europe and in other jurisdictions covering mesenchymal stem cells, mesenchymal stromal cells, and their various markers, et cetera, for use in acute respiratory distress syndrome. We believe we've got the leading intellectual property portfolio for mesenchymal lineage cells in the treatment of inflammatory lung diseases. Those are long-lasting and extensive and granted. We are proceeding with, as I've mentioned earlier, with moving towards a pivotal study, with the aim of receiving emergency use authorization in COVID ARDS, and then we will work towards broadening that in other indications, non-COVID related ARDS. We believe we are the leaders in this space, both in terms of patient data, but as well as intellectual property.
We think that others will have to work around us or with us to access or have issues with our intellectual property.
Thanks, Silviu. The next question is beyond the expected feedback from FDA on chronic low back pain, what are the next steps in the program?
Clearly having the FDA opine on the type of clinical study that needs to be put in place is critical. Together with a partner in Europe, we are expecting the feedback from the agency will allow us to put in place a pivotal trial that is focused on both U.S. FDA approval as well as supporting EU approval. Until we get that feedback, we won't be able to make that clear. We’re very confident that we understand what the FDA needs in terms of a pivotal trial design.
Thanks, Silviu. Next question is the proposed new COVID trial likely to again exclude non-mechanically ventilated patients given that biomarkers can now identify likelihood of progression to severe ARDS?
That's a very broad question, I think. I think the most important issue here is where is the continued severe unmet need, and where have we demonstrated a survival benefit, and how best to position a program for the most rapid confirmation and the most rapid likelihood of an EUA approval. Patients on ventilators continue to have the highest mortality, and that has not changed over the past two years. What has changed with the vaccines, of course, is that the proportion of patients who on infection end up hospitalized and then into the ICU on ventilators has dropped by maybe 75%. 75% reduction remains, continues, especially in the Western world, with a very large patient population that continues to be in hospital and ultimately requiring ventilators.
That's a population that continues to have the same level of high risk for mortality since the only approved drug in ventilator patients is dexamethasone. We think we understand what the FDA requires in terms of an endpoint. It would have to be a trial that mimics, reproduces or confirms the data that was generated in the last study in patients who were relatively younger, under the age of 65, with an endpoint of mortality benefit through 60 days. Whether the cells then also provide a potential benefit in patients who are hospitalized but are not yet on a ventilator is a study that we would continue to consider and evaluate together with a potential strategic partner.
It's whether we can prevent progression from pneumonia to requiring ventilation in ARDS is something that we'll be very interested in and potentially an area that would require an even lower dose of our cells than we're currently anticipating for ventilated patients. That'll be the basis of further evaluation as we move forward.
Thanks, Silviu. The next question is, many of our trials thus far seem based on a single dose. Would you consider additional trials with multiple dosing in the future, for example, in ARDS and the heart space?
I think the results in the ARDS study demonstrate that two doses within five days has given us a substantial reduction in mortality in patients who are appropriately targeted with the degree of inflammation that was associated with a younger age group. I think we're understanding now that inflammation is key to both outcomes and response, as was seen most recently in the heart failure trial with levels of CRP. Defining the biomarker levels of a particular patient and considering how best to adjust dosage in different age groups is something we'll focus on in the future. I think that patients who are beyond the age of 65 with COVID have a very high level of inflammation, and that's where potentially higher dosing may be required.
That will be the basis of additional phase II exploratory studies. We think that we've identified the appropriate dose for younger patients with COVID-19-related ARDS. With respect to heart failure, I think it's quite evident that with the outcomes that we've established, three-point MACE, cardiovascular death, heart attacks or stroke, a single intervention with 150 million cells has made a substantial reduction. A 65% reduction in those outcomes is unheard of with other therapies. In fact, other therapies that have been approved in high-risk patients for a reduction of the same three-point MACE endpoint give outcomes of the order of around less than 10%. If we can reproduce those data with a single intervention, I think that we would be a standout product.
I don't see any reason for any further additional doses in that particular disease. It depends on the degree of inflammation that one is targeting, and I think part of our phase II and phase III strategic application is to identify appropriate dosage. Dr. Grossman, would you like to add to those statements?
Yeah. I think very clearly across all of our programs, given the data analysis that we've completed, we've essentially defined the appropriate population and the best dose, particularly in those that are more likely to respond. Whether it's chronic low back pain, heart failure, or COVID ARDS, we clearly define the population that responds most to the current doses that we're using, and we're moving forward in all of those programs and, as you know, are in discussions with the FDA. Regarding the populations that didn't have the same response as Silviu mentioned, those over 65, we clearly believe that this is a dosing issue and will be studying a different higher dose in that population.
We are now working with really the world's experts to put together our ongoing protocols moving forward, and we'll be able to report to you soon what those are and when they will start.
Thank you, Silviu and Fred. The last online question we've received is: Where does MPC-300-IV, diabetes, and RA sit in this great scheme of things? Is the company still interested in these spaces going forward?
Thank you for that question. I think what that begins to address is really the pipeline development, strategic pipeline development. I think we are in some ways very fortunate that each of the areas that we've focused on in the past few years, and most importantly, the results that we've collected in the last 12 months, have identified, as Fred just said, the appropriate target populations, the appropriate dosage, the appropriate indications. We are now in the position where we will, as a management team and board, sit down over the next couple of months and do a strategic evaluation of our portfolio from top to bottom to identify the greatest likelihood of success, the shortest time to commercialization on a product-by-product basis. We have to make rational decisions.
We do not have unlimited resources. We have very focused resources, and we will put those resources behind those indications first that get us to market and bring revenue to the company as we should be doing. It's clear that other indications in phase II, for example, have great potential and they all form part of the overall strategic portfolio evaluation and recommendations. I think that's exactly what shareholders would expect us to do as a maturing company that moves from the development stage to commercialization.
Thanks, Silviu. There are no more online questions. Are there any telephone questions? Thank you. There are no questions on the phone line.
If there are no further questions, I'd like to hand over to our chairman. Joe Swedish, would you like to make some concluding statements, please, Joe? Thank you.
Yes, I would like to just offer one reflective moment. Earlier, Donal O'Dwyer was very thoughtful in commenting on his service to the board, and Michael Spooner obviously did not have a chance to weigh in. I'm sure he would echo the very same sentiment, and I just wanna take a moment to acknowledge not only Mr. Dwyer's service to the board, but also Mr. Spooner. Both have been remarkably gifted board members who increase the value for our shareholders as well as serve in a fiduciary role regarding protecting the assets of the company and continuing to grow the company on a very strong trajectory given the R&D commitments and efforts that have been applied over many years.
I thank them for their service over many years and as they depart over the coming twelve months and wish them well. Again, they will be missed, and especially the talent that they've contributed to the committees that they have served. With that said, I'm ready to close the meeting. Thank you very much for all in attendance, and I hereby declare the meeting adjourned.