Mesoblast - Q3 2023

Transcript

Operator (participant)

Thank you all for standing by. Hello, welcome to the Mesoblast financial results for the period ended March 31st, 2023. An announcement and presentation have been lodged with the ASX and will also be available on the Home and Investor pages at www.mesoblast.com. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. As a reminder, this conference is being recorded. 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 filing with the SEC, which could cause actual results to differ materially from those and such forward-looking statements.

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

Silviu Itescu (CEO)

Thank you, operator. Good afternoon, good morning to everybody on the call, to our operational highlights and financial results for the quarter ended March 31, 2023. If we could go to slide four, please. On the call with me today is our Chief Medical Officer, Dr. Eric Rose, and our Interim Chief Financial Officer, Andrew Chaponnel. Slide four shows a snapshot of the investment highlights. We have a novel allogeneic cell therapy platform, with two lead candidates, both being platforms for multiple products and indications. remestemcel-L, rexlemestrocel-L, each have got their own specific indications. I'll be talking in detail in this presentation on both of those platforms. Financially, we have substantial cash on hand, and there'll be a detailed presentation by Andrew Chaponnel on our finances for the quarter. Next slide, please. Slide five.

This slide is a summary of our late-stage clinical pipeline based on our mesenchymal stromal cell platforms. As you can see, remestemcel-L for pediatric steroid-refractory GvHD, Graft-versus-host disease, is the most advanced and is currently before the FDA, with the review of the BLA with a PDUFA goal date of August 2, 2023. The manufacturing inspection has been conducted, and I'll talk more about that shortly. remestemcel-L is also being developed for adult steroid-refractory Graft-versus-host disease, acute respiratory distress syndrome, and inflammatory bowel disease. rexlemestrocel-L, our second generation, stromal cell platform, is being developed for chronic inflammatory low back pain, discogenic low back pain, and rexlemestrocel-L is also being developed for inflammatory heart failure. For both these indications, the FDA has granted Regenerative Medicine Advanced Therapy designations.

We can now go to the next slide, and I'll hand over to Andrew to talk about our financial results, please.

Andrew Chaponnel (Interim CFO)

Thanks, Silviu. If you complete turn to the financial highlights for the third quarter of FY 2023 on slide seven. For the quarter, revenue from royalties on sales of TEMCELL in Japan by our licensee were $1.8 million. On a constant currency basis, royalties grew 4% in the quarter to $2 million. For the 12 months, we recognized $7 million of royalties and product sales. Net cash usage for operating activities in the third quarter was $16 million. This represented a 4% increase from the third quarter of FY 2022, and a 34% reduction of $8.3 million from the third quarter of FY 2021. In April, we successfully completed a global private placement of $40 million for existing major U.S., U.K., and Australian shareholders.

As of March 31, 2023, cash on hand was $48.8 million. We have pro forma cash of $80.8 million after adjusting the proceeds of $40 million raised in the April private placement. We also have up to an additional $40 million available from debt from existing finance facilities, subject to achieving certain milestones. Turning to slide eight, you'll see we are reporting an improved loss before tax for the quarter. Revenue is predominantly from royalties on sale of TEMCELL in Japan, despite an increase in underlying sales volume of 4% in the 3rd quarter of FY 2023 compared to the 3rd quarter of FY 2022, reported revenue decreased slightly given the Japanese yen has appreciated against the US dollar. Our R&D expenditure was reduced by 14% for the quarter.

Our R&D spend in the quarter was primarily to support the remestemcel-L BLA resubmission and preparation for pivotal studies of rexlemestrocel-L. We continued our investment in manufacturing activities to support the potential launch of remestemcel-L for the treatment of steroid-refractory acute GvHD. On FDA approval, $31 million of remestemcel-L relaunch inventory will be recognized on the balance sheet. Finance costs for the quarter includes $3.8 million of non-cash expenditure, comprising accruing interest and borrowing costs. Now I'll hand the call back to Silviu for the remainder of the presentation.

Silviu Itescu (CEO)

Thanks, Andrew. Slide 10, please. This slide summarizes the mechanistic process that is acute graft-versus-host disease, a fatal complication of an allogeneic bone marrow transplant. Essentially, following chemotherapy, there is extensive tissue damage in the patient who subsequently receives an unrelated donor bone marrow transplant. The transplant then attacks the body through defined pathways that are driven by T cells. T cells are activated. They're the orchestrator of multiple cytokines produced by other cell types, resulting in a cytokine storm, which is destructive for the gut, the liver, the skin, and other organs. In those patients who have the most severe organ disease, mortality approaches 90%. Can we go to slide 11, please? The market opportunity for Mesoblast is large. More than 30,000 allogeneic bone marrow transplants are performed globally. Of these, about 20% are pediatric.

We are targeting the most severe cases, initially targeting pediatric GvHD, and intend to target the more severe adult cases as well. Next slide, please. Slide 12 summarizes the survival data across three different studies involving more than 300 children treated with remestemcel-L. These studies were designed to demonstrate whether remestemcel-L provided an early survival benefit. The three studies outlined here include a randomized controlled subset of 27 children within an earlier study called Protocol 280. The 2nd study was our pivotal phase III trial, called Study 001, and the 3rd study was an expanded access protocol of 241 children who received remestemcel-L, having failed other available therapies.

What you can see here is that in each of the three studies, there was substantial early survival benefit, from 66% in the sickest children, where remestemcel-L was used as salvage therapy to 79% in the randomized controlled subgroup study. The comparators for each of these outcomes showed substantially lower survival outcomes at day 100, from 54%-57%. In the EAP 275 study, a subset analysis, comparing outcomes in Grade D disease, the most severe form of the disease, against survival in the database at the International Bone Marrow Transplant Registry, showed a significant survival benefit of 51% in those who received remestemcel-L, versus just 31% in those who received best available therapy.

Across all of these studies, there's evidence of early day 100 survival benefit using remestemcel-L. Can we go to the next slide? In newer data that's now before the FDA, analysis of survival through day 100 through day 180, six months in the pivotal phase III trial in patients with the highest risk for mortality, those with biomarkers, the MAP biomarker scores above 0.29, demonstrated a significant survival benefit compared to a propensity-matched control cohort, the so-called MAGIC cohort. You can see that in the control children treated with best available therapy, only 10% were alive beyond three months, compared to 67% alive in those who received remestemcel-L. Next slide, please. Slide 14. What is the status of our BLA for remestemcel-L in pediatric patients with steroid-refractory acute GvHD?

The new data under review by the FDA are outlined on this slide. The BLA was resubmitted in January 30th. The BLA file was considered by the FDA to be a complete response, was accepted for review, and we were given a PDUFA goal date of August 2, 2023. The new data under review shows durable long-term survival of patients in the phase III trial, increased survival in high-risk patients compared with propensity-matched controls, and a positive correlation between in vitro potency assay and survival. Additional data that the FDA is reviewing shows that the validated potency assay has low variability and can adequately demonstrate manufacturing consistency and reproducibility. Next slide, please. Today we announced that the manufacturing inspection of the remestemcel-L process has been conducted by the FDA. The FDA inspection did not result in the issuance of any Form 483.

Form 483 is always provided at the conclusion of an inspection if investigators have observed any conditions that, in their judgment, may constitute violations of the FDA Cosmetic Act and related acts. We were very pleased that no issuance of a Form 483 was provided. The Establishment Inspection Report, or the EIR, is expected to be issued by the FDA in the coming weeks, which will provide a detailed summary and a final assessment of the inspection. Next slide, please. Slide 16. Mesoblast provided new results from a four-year observational survival study performed by the Center for International Blood and Marrow Transplant Research, CIBMTR, on 51 valuable patients with acute GvHD who were enrolled in our phase III clinical trial, remestemcel-L. These data provide a cornerstone of our BLA resubmission.

Overall survival in the remestemcel-L cohort was 63% in one year, 51% at two years, and remained roughly at that level through at least four years and beyond. In other words, approximately 50% of children with this very fatal disease, of whom, almost 90% were Grade C, D disease, are alive, not just at two years, but for as long as the follow-up has allowed us to, evaluate the outcomes. These data provide assurance that the short-term responses and early survival through 180 days previously shown to the FDA in the BLA submitted previously, are unlikely to have arisen by chance. These long-term survival outcomes really are a cornerstone of our BLA resubmission. Next slide. Slide 17.

This slide shows a comparison between two-year outcomes on the right with remestemcel-L from our phase III trial, 51% survival, against the largest pediatric cohort study published to date, which is the MacMillan study on the left from the University of Minnesota, showing just 35% survival in children with steroid-refractory disease. It's important to point out that in the MacMillan study on the left, children were treated with best available therapy. Only 22% had Grade 3/4 disease, whereas 89% of our study on the right had Grade C, D disease, a same level of severity. Very different patient populations, much more severe in the remestemcel-L treatment, and yet survival through 24 months substantially improved. We can go to the next slide, please. Slide 18.

This summarizes, again, the long-term survival data in the column with dark blue over four years, against four studies that have been recently published between 2020 and 2022. The McSweeney study I've already described, in addition, there are four other studies that relate to adults with steroid-refractory acute graft-versus-host disease. Whilst they all have lower levels of severity in terms of patients with Grade 3/4 disease, in comparison to our phase III trial, the relative two-year survival in each of these studies is of the order of between 25%-38%, comparing to 51% of two-year outcomes in our phase III trial.

We believe that the long-term survival that we're seeing in GVHD001 treated patients with remestemcel-L provides a durable long-term outcome that is not comparable with any of the recently performed studies, including those with ruxolitinib. Next slide, please. Slide 19. Now moving from new clinical data to new data around potency, which is part of the BLA submission. It's important to note that the primary mechanism by which GvHD progresses is due to alloreactive T cell activation, T cell proliferation, and orchestration, as I mentioned earlier, of inflammatory cytokine production by these activated T cells. An in vitro assay measuring inhibition of T cell activation was established during development of remestemcel-L prior to the phase III trial as a potential measure of product potency.

This assay was used to measure the ability of individual remestemcel-L lots to inhibit T cell activation prior to their use in both the EAP 275 and prior to the phase III trial, GVHD001. We therefore evaluated and established correlations between survival outcomes in these two pediatric studies with potency of the lots that the children received, as measured by inhibition of T cell activation, and these correlative analyses have been presented to the FDA. Slide 20, next slide, is a representation of some of these potency data which were presented earlier this year at the tandem meetings of the Bone Marrow Transplant Society.

As can be seen in the capitalized line on the right, there was an association between higher levels of inhibition of T-cell activation by product lots received and day 180 survival, such that those patients who got product above the median had 85% survival versus those who got product below the median. This establishes that the greater the potency of products received in the phase III, the greater the survival outcome. Further subgroup analyses, looking at patients by higher risk severity, including the Minnesota high-risk category, the MAGIC algorithm score above 0.29, and Grade D disease. All of these subgroup analyses, product lots with potency above the median were associated with higher survival than product lots with potency below the median.

I think it's important, however, to also note that particularly with Grade D disease, even products with lower levels of potency gave survival outcomes of 50%, which is substantially higher than the expected survival for Grade D disease in the CIBMTR registry using best available therapy, where the that survival outcome is only 30%. Even a lower potency product have substantially higher survival than best available therapy, and of course, the relationship between potency and survival is now established through the phase III trial. If we go to slide 21, the next slide, we then re-evaluated survival outcomes in the EAP study, one single study, by the presence of our newly established improved manufacturing product that is now called Ryoncil, with the product produced prior to 2008 that was called Prochymal.

That product had a lower potency as measured by our current potency assay than the new product, Ryoncil. What you see here on this slide, on the left-hand side, is survival through 100 days in those children who had failed all other therapies in our EAP program by Prochymal versus Ryoncil treatment. As you can see, a significantly higher survival, 74%, was achieved with Ryoncil than was achieved with Prochymal, 56%. Even more important, if you can look on the figure on the right, this survival benefit with the improved manufactured product, Ryoncil, is even more significant in those patients at highest risk of mortality, those with Grade D disease. In 106 patients with Grade D disease, Ryoncil achieved a 72% survival, whereas Prochymal, the lower potency product, achieved only 44% survival.

These studies, these analyses within a single protocol, the expanded access protocol, is able to establish not only that we have a potency assay that predicts survival at the level mechanistically of T cell activation, the primary mechanism of action for GvHD, but it is able to also delineate higher potency products from lower potency products and their relationship to improved survival. Next slide, please, slide 22. Those having summarized those data, the new data that form part of the BLA. Let's talk now about our go-to-market strategy with the assumption, hopefully, that a PDUFA after August is, gives us a positive outcome. The pre-launch activities that are active and ongoing are engagement of the highest transplant volume centers with experience using Ryoncil.

Non-promotional activities include profiling of the centers, education on disease awareness, unmet needs, and support for payer engagement. We are currently hiring select positions to build out a small commercial team. The key activities of this team are market access to initiate payer outreach, medical, providing education to payers, corporate leadership initiating engagement with the top 15 centers, and regional sales directors leading center profiling. Importantly, manufacturing preparation has been ongoing throughout, with $31 million of remestemcel-L pre-launch inventory in hand. Go to slide 23. The post-approval launch activities are intended to be a staged approach, initially targeting the highest transplant volume centers. those centers are those not only with highest volume, but also with experience with our product.

The plan is to build out an efficient, targeted sales force with understanding the 15 highest volume transplant centers account for about 50% of all patients. The key activities post-approval will be to initiate commercial onboarding and logistics, MSLs engaging the centers around medical and scientific needs, logistical and reimbursement support offered as needed, and center certification on a center-by-center basis for remestemcel-L administration. Having now covered where we are with remestemcel-L, let's move to rexlemestrocel-L, our next-generation product for chronic low back pain and for inflammatory heart disease. Slide 25. We've said previously, of course, that discogenic back pain impacts large numbers of patients, both in the U.S. and in the EU.

In the U.S. alone, it impacts 7 million patients in each of the U.S. and EU5, and that's our target market. Very well-defined patients who have underlying degenerative disc disease as the cause of their chronic pain. It's important that 50% of opioid prescriptions are for chronic lower back pain due to this condition. We expect that if we have a successful treatment here, we might have an important impact on the opioid epidemic. Let's go to slide 26. The summary of the program is outlined on this slide. We've gained alignment with the FDA on the appropriate pivotal phase III study, which seeks to replicate the significant reduction in pain that was seen as early as 12 months and through up to 36 months in our first phase III trial.

FDA has agreed with our plans for pain reduction through 12 months as the primary endpoint of the pivotal trial, and with function, functional improvement and reduction in opioid use as the key secondary endpoints. The planned phase III program will include additional 20% of patients recruited across the EU to support regulatory submissions simultaneously or in close sequence to both FDA and EMA. We have an RMAT designation for discogenic low back pain received from the FDA earlier this year in February, we expect to commence patient enrollment in the third quarter of this year. Next slide, please, 27. The RMAT designation that we received from FDA provides all the benefits of both breakthrough and fast track designations, including a rolling review and eligibility for priority review on filing of a BLA.

The objective of the pivotal trial is to replicate as closely as possible, the data that we obtained from the first phase III trial, which showed that a single injection of rexlemestrocel-L into the lumbar disc resulted in significant reduction in pain relative to saline controls as early as 12 months, throughout 24 months and throughout 36 months in a 404 patient study. The pain reduction for 36 months was also seen in the subset of patients who were using opioids at baseline. They were not insignificant, 168 patients. In this group, there was substantially greater reduction at all time points in pain compared with saline controls.

Very importantly, at the end of the 36-month follow-up, 28% of patients who had received rexlemestrocel-L, together with its carrier, HA, were not taking opioids, compared with only 8% of saline-treated controls. This is a very important observation that we think is critical to evaluate again, prospectively in the pivotal trial. Slide 28 is a snapshot of the reduction in pain that was seen in the first study, and it was maximal in those patients who had pain with duration below the median for the whole trial, which was approximately 68 months. Therefore, this group of patients is likely to have had the highest levels of inflammation. The target in the pivotal trial will be this group of patients with pain for up to five years.

As the objective is to address as early as possible this very large unmet medical need, where we think that the likelihood of treatment response is greatest. Finally, let me move to the last couple of slides that address our cardiac program in inflammatory heart disease. Cardiovascular disease remains a leading cause of death in the U.S., particularly those patients with the more advanced forms of heart failure, and heart damage, who finally progress either to mortality or an LVAD or a transplant. If we go to slide 31, please. We have an existing Regenerative Medicine Advanced Therapy designation to cover the use of our cells in the most severe patients, those who have an LVAD in place.

We really believe that there's a continuum of disease that rexlemestrocel-L is likely to be beneficial in, and that the continuum is from patients in classes two, three, and four, defined by very high levels of biomarkers of severity, such as NT-proBNP, and markers of inflammation such as CRP, and as well as those patients who then finally move into end-stage disease, who have an LVAD in place. That's our target market. Slide 32 is a summary of new data that were published this quarter in the premier journal, cardiovascular journal, Journal of the American College of Cardiology. Data from the 537 patient phase III trial called DREAM Heart Failure, which followed severely advanced patients with heart failure for up to 30 months of follow-up.

The key outcomes that were published in this important publication was that left ventricular ejection fraction was significantly improved from baseline through 12 months in those patients, particularly in those with evidence of inflammation. The major complications of heart attacks or stroke were reduced by 57% in all treated patients and by 75% in those with inflammation. The so-called three-point MACE, major adverse cardiac event rate in patients, which includes the endpoint of cardiovascular death reduction, was reduced in those with inflammation by 37%. These results were spectacular, and we're very excited about these results and the implication for patients with severe disease.

If we go to slide 33, the overall totality of data, 159 patients in LVAD study number two, and 537 patients in DREAM heart failure, are now being evaluated in totality for a continuum of mechanistic data that may allow us to structure a pivotal trial as we talk to the FDA about pathways towards approval. On that note, I think I'll stop and open this to questions, please.

Operator (participant)

Thank you. If you'd like to ask a question, you'll please need to press star one on your telephone and wait for your name to be announced. If you'd like to cancel your request, please press star two. If you are using a speakerphone, please pick up the handset to ask your question. Your first question comes from Edward Tenthoff from Piper Sandler. Please go ahead.

Edward Tenthoff (Managing Director and Senior Research Analyst)

Great. Thank you, guys, and thanks for the detail on the presentation. My friend Mike was wondering what still has to be done for the head of the NDA. Are there any remaining pieces that need to be filed or any interactions with the FDA? At this point, are we really just waiting for the PDUFA date? Thanks.

Silviu Itescu (CEO)

Well, having completed the manufacturing inspection, which was the biggest item still outstanding, we continue to interact with FDA on a variety of questions that backwards and forwards in regard to the review. Other than that, really, the major item that remains outstanding is a discussion around the specifics of the label. That's really, it still remains ahead of us, and, we're very excited as we proceed towards the PDUFA date.

Edward Tenthoff (Managing Director and Senior Research Analyst)

Absolutely. Well, excited for upcoming approval. Then when it comes to lower back pain, what are the steps in order to initiate that phase right? That's such an exciting opportunity. Thanks.

Silviu Itescu (CEO)

We have alignment with the FDA on the protocol itself. We've already manufactured product for the trial. We will be having a discussion with the FDA under the RMAT designation to ensure that we have our approach aligned in terms of manufacturing potency and the like. Those we'll be proceeding in parallel with commencement of the study. We expect to initiate enrollment across about 40 sites in the U.S. in the third quarter, calendar quarter. We're on track to get things going.

Edward Tenthoff (Managing Director and Senior Research Analyst)

Awesome. Great news. Thanks, Silviu.

Silviu Itescu (CEO)

Thank you.

Operator (participant)

Thank you. Your next question comes from Louise Chen from Cantor Fitzgerald. Please go ahead.

Carvey Leung (Analyst)

Hello, everyone. This is Carvey on for Louise Chen from Cantor Fitzgerald. Thank you for taking our questions. First, your PDUFA, your PDUFA date is fast approaching. If approved, how quickly can you commercialize the product? Secondly, how are you thinking about OpEx for the rest of 2023 and 2024 fiscal years? Thank you.

Silviu Itescu (CEO)

We have a, the commercial team that is currently in place and building. It will not need a very large footprint. We expect to have about 15 or so sales force in place at the time of launch. The launch is gonna be a targeted launch, initially focusing on the highest volume transplant centers, but we should be ready to launch as soon as we're approved. We've already got inventory in place. The discussions are ongoing now with payers. Reimbursement will take some time, of course, but we should be in a position to initiate launch as soon as we're approved, although the pace of the launch is going to be staged.

In terms of CapEx, I think you asked, or OpEx, rather, we don't see in the short term, changes in quarterly spend, other than as we have product approved, we will be looking towards label extension, particularly in adult GvHD, as the first cab off the rank. How we fund that program is really a flexible possibility. We have access to additional capital through our financial structures that are currently in place through debt. We have are in discussions with various strategic financial partners around royalty-based structures, et cetera.

In general, I think our plan, at the moment is to maintain the current OpEx spend on a quarterly basis.

Carvey Leung (Analyst)

Got it. Thank you. looking forward to the PDUFA date. Congrats on the progress. Thank you.

Operator (participant)

Thank you. Once again, if you'd like to ask a question, you need to press the star key followed by the number one on your telephone keypad. Your next question comes from Sami Corwin from William Blair.

Sami Corwin (Research Analyst)

Hi there.

Operator (participant)

Go ahead.

Sami Corwin (Research Analyst)

Thanks for taking my question. Hi, thanks for taking my question. I was curious if there are any other possible alternatives in terms of the outcome for the EIR, other than the FDA just kind of giving you guys a thumbs up? With regards to the study in steroid refractory aGvHD in adults, how exactly could that trial differ from Study 001 and Study 280 in terms of design and potential endpoints? Thank you.

Silviu Itescu (CEO)

Okay, thank you. The first question was about the expected EIR in the next couple of weeks on the manufacturing inspection. look, you know, it's hard to anticipate what the observations and the final determinations of the FDA are on a manufacturing inspection. I will say that a Form 483, can only be provided at the end of the inspection when the FDA and the facility and the company are face to face. A Form 483 was not provided, so that cannot be provided later. so we're very pleased by that. In other words, there are no official outcomes that would've been required for improvements under a Form 483.

There may be other, small issues that come up in the EIR, that's the final document, but the kind of major concerns that are in a Form 483 will not be there. With respect to an adult program, I might just ask Eric. Eric, would you like to comment on how you see an adult program going forward?

Eric Rose (Chief Medical Officer)

Can you hear me?

Silviu Itescu (CEO)

Yes, we can.

Eric Rose (Chief Medical Officer)

Good. We have had intense interest in our product on the part of adult oncologists that face the same problem as the pediatric oncologists. What type of trial we're discussing with members of the CIBMTR now, there is a clinical trials group that is supported by the NIH, that we're in discussion with, about doing a trial in adults that presumably will allow extension of the label to that age group as well. The design of such a trial is still outstanding.

Silviu Itescu (CEO)

I think we have flexibility in thinking about the degree of severity in the adults, whether we use a randomized control design or whether we use a propensity matched control design. I think all of those are on the table. They will form part of our ongoing discussions with the FDA.

Eric Rose (Chief Medical Officer)

Yeah.

Sami Corwin (Research Analyst)

Great. Then just one more, if I can. Considering you plan on running two phase III trials and potentially launching the aGvHD product, do you think you have enough cash on hand to accomplish all near-term milestones? Thank you.

Silviu Itescu (CEO)

Yeah. As I said earlier, there are multiple alternative ways by which we may fund these various trials. They include collaborations, as Eric just mentioned, with academic groups like the NIH or registries like CIBMTR, for example. That would have a substantial impact on our resource allocation. Secondly, there are financial groups that we're in discussions with, who are interested in potentially royalty-based structures that would again, defer our spend requirements. Thirdly, we have access to up to an additional $40 million in pre-arranged debt structures with our existing facilities that become available post FDA approval should we want to access them.

Sami Corwin (Research Analyst)

Great. Thank you, and congrats on the progress.

Silviu Itescu (CEO)

Thank you.

Operator (participant)

Thank you. Once again, if you'd like to ask a question, please press star one and wait for your name to be announced. Your next question comes from John Hester from Bell Potter. Please go ahead.

John Hester (Senior Healthcare Equities Analyst)

Yeah, good morning, Silviu Itescu. Just wanted to take you back to slide 21 on the right-hand side of that chart, which talks about the Grade D Expanded Access Program, a 100 survival rate.

Silviu Itescu (CEO)

Yes.

John Hester (Senior Healthcare Equities Analyst)

In the Ryoncil line, that suggests that the survival rate there was 72%, and that's in the Grade D patients who are the sickest of the sick. Just confirm for me, is that the Ryoncil product, that was the product that was used in your clinical trial, correct?

Silviu Itescu (CEO)

That is that.

John Hester (Senior Healthcare Equities Analyst)

Yeah. What's the difference between that survival rate, 72%, and the 53%, I think it was, or 51% in the down on page 18?

Silviu Itescu (CEO)

Yes. That 50%. Yeah. I'm sorry, on slide 18.

John Hester (Senior Healthcare Equities Analyst)

The survival?

Silviu Itescu (CEO)

Yeah, that's 51% at two years.

John Hester (Senior Healthcare Equities Analyst)

Yeah.

Silviu Itescu (CEO)

The data that we're talking about here in, on slide 21, is 72% at three months, day 100.

John Hester (Senior Healthcare Equities Analyst)

Mm. Mm, okay.

Silviu Itescu (CEO)

That's right. It's early survival data in the EAP, which only followed up children to 100 days. The longer term survival of our phase III trial is now out to four years. Even a 51% two-year survival rate is substantially greater than the survival in the mid-20s to mid-30s, with best available therapy, which includes ruxolitinib in other studies.

John Hester (Senior Healthcare Equities Analyst)

Is there any confusion now as to the level of potency that the product that has been manufactured in recent years will deliver? This analysis indicates there was a significant difference between the earlier Prochymal product and the Ryoncil product. I suppose.

Silviu Itescu (CEO)

That's precisely the point. That's exactly the point. The clarification has come through the analysis that demonstrates that improvement in manufacturing, changes in manufacturing, which were implemented in, you know, a particular point in time in the development history of the product, delineates a more potent product currently in use in our studies from the less potent product that was called Prochymal, that failed in other earlier studies. We believe that the reason that we're seeing greater clinical outcomes with our newly improved product, is because of its greater potency as measured by our validated potency assay. That is very encouraging, both in terms of the pediatric data and the data that we expect to generate in adults.

John Hester (Senior Healthcare Equities Analyst)

To what extent has that new data on the potency been available in over the last two years since the complete response letter, or has that always been available?

Silviu Itescu (CEO)

No, these are data that are newly generated as part of the BLA resubmission in alignment with optimization of the potency assay. The assay itself has been in place and was in place when products were being used in both the EAP and the phase III trial. What this provides us now is an understanding of how changes in manufacturing have resulted in a more potent product, which correlates with better survival.

John Hester (Senior Healthcare Equities Analyst)

Okay. And just finally, during the inspection of the plant in Singapore, was the inspectors able to see product being manufactured at that time?

Silviu Itescu (CEO)

Yes.

John Hester (Senior Healthcare Equities Analyst)

I assume that they were. Yeah.

Silviu Itescu (CEO)

Yes. The reason for the inspection, is that, four inspectors were on site and observing the entire manufacturing process from beginning to end over a 10-day period. Every detail of the manufacturing process was observed and inspected.

John Hester (Senior Healthcare Equities Analyst)

Excellent. That's all for me. Thank you.

Silviu Itescu (CEO)

Thank you.

Operator (participant)

Thank you. As there are no further questions at this time, that brings us to an end of today's call. I'm going to hand back to Dr. Itescu for any closing remarks.

Silviu Itescu (CEO)

Great. Thank you, everybody, for joining us today. We're very excited about how the process is evolving on the BLA resubmission and our very collaborative interactions with the FDA. We look forward to the upcoming PDUFA decision date as we build out our plans for a hopefully a successful outcome and a post-approval launch. Thank you, everybody.

Operator (participant)

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