Mesoblast Limited (MESO) Q4 2022 Earnings Report, Transcript and Summary

Thank you for standing by. And welcome to the Mesoblast Limited 2022 Full Year Financial Results Conference Call. All participants are in a listen-only mode. A presentation followed by a question-and-answer session [Operator Instructions]. I would now like to hand the conference over to Dr. Silviu Itescu, Chief Executive. Please go ahead.

Thank you very much, and hello, everybody. Welcome to the operational highlights and financial results for the yearend of June 30 of 2022 for Mesoblast. With me today, are our Chief Medical Officer Dr. Eric Rose, and our Interim Chief Financial Officer, Andrew Chaponnel. We can go straight to Slide 4 please. This slide is a snapshot of our late stage clinical pipeline. We have two lead products. Our first generation product is Remestemcel in red. And our next generation product is our immunoselected platform technology, Rexlemestrocel cell, both are stromal cells allogeneic products being developed for distinct indications. Remestemcel is being developed for acute graft versus host disease, steroid-refractory, in children, and then to be expanded into adults. It has completed Phase 3, and we will talk in great detail about our plans for the resubmission for this product for this indication. The second follow-on indication for Remestemcel is in acute respiratory distress syndrome, initially targeting patients with COVID-19. Our third indication is for inflammatory bowel disease, biologic refractory Crohn's and ulcerative colitis. Rexlemestrocel is being developed for local delivery to target inflammation in patients with severe unremitting chronic low back pain due to inflammatory degenerative disc disease, is currently in Phase 3 development and Rexlemestrocel is also being developed for inflammatory chronic heart failure in patients with reduced ejection fraction, also in Phase 3 development. If we go to the next slide please. Near term milestones for these two platform technologies are highlighted in this slide. Remestemcel is in line for a BLA resubmission, which we expect to be filed this quarter for children with steroid refractory acute graft versus host disease. And if accepted with potential U.S. approval for this project in Q1 calendar year 2023. Secondly, we're working with Vanderbilt University Medical Center which coordinates a clinical trial network across 40 sites in the U.S. focused on acute respiratory distress syndrome to jointly develop a trial protocol focusing on confirming the previously observed reduction in mortality in COVID-19 page patients with ARDS under the age of 65. Rexlemestrocel has two major upcoming milestones. One is to meet with the FDA in the next quarter, under the existing regenerative medicine advanced therapy designation, RMAT to discuss a common mechanism of action in patients with heart failure with reduced ejection fraction and a potential pathway towards regulatory approval. With respect to our back pain program, we already have alignment with the FDA on what a pivotal confirmatory study would look like and expect to commence that study by the end of this year in patients with severe unremitting lower back pain due to degenerative disc disease. We can now move to the financial results. Andrew, could you please take us through the financial results for the period ended June 30.

Thanks Silviu. Now turning to Slide 7, total revenue from royalties and milestones increased by 37% to $10.2 million for FY22 compared to $7.5 million for FY21. Within total revenue, royalties from sales of TEMCELL in Japan by our licensee in FY22 were $8.7 million and $9.8 million when adjusted on a constant currency basis, increases of 21% and 36%, respectively versus FY21, predominantly due to increased volume of products sold. At June 30, 2022, cash on hand was $60 million, with pro forma cash of $105 million after we raised gross proceeds of $45 million via a private placement in August 2022. We also have up to an additional $40 million available from our existing loan facility subject to certain milestones. For the year ended June 30, 2022 net cash usage reported for operating activities was $65.8 million, a reduction of 35% on the comparative period last year. Now if we turn to Slide 8, you can see a chart that details reduction in our net cash burn. Our quarterly net operating cash burn has been reduced quarter-on-quarter for the last six quarters. We turn now to Slide 9 thanks. We can see the P&L result for the year compared to the prior year. Within R&D expenditure, there was a 38% reduction of $20.2 million predominantly due to reduced spend on clinical trial activities. We continue our steady investment in manufacturing, including production of Remestemcel inventory, to support the potential launch of GVHD. To-date, we have manufactured $28.9 million worth of Remestemcel inventory, in anticipation of launch. This pre-launch inventory will be recognized on the balance sheet, if we receive FDA approval. Our finance costs have increased. But I note that interest paid in cash was $6.1 million for FY22 and $5.9 million for FY21. And the increase in our reported finance costs is primarily due to the recognition of a non-cash gain on revaluation of our borrowings in a comparative year, due to a reduction in the expected value of future repayments. Now I'll hand the call back to Silviu for the remainder of the presentation.

Thank you, Andrew. We can move now to Slide 11 please, as we start to talk in more detail about our pipeline. Steroid-Refractory Acute Graft versus Host Disease continues to be a devastating disease with a significant unmet need because of its high mortality. The burden of illness continues to be high with about 50% of patients who receive an allogeneic bone marrow transplant developing Acute Graft versus Host Disease and about 50% of those being non-responsive to steroids. In particular, the more severe forms of steroid refractory aGVHD is associated with mortality rates as high as 90% and significant extended hospital stay costs. The market opportunity therefore, is substantial. And in particular, we have gained very good insight into how mesenchymal stromal cell product is likely to be adopted and accepted by the physician community based on the penetration in the Japanese market by TEMCELL. The mesenchymal stromal cell product under license is sold by our partner in Japan, JCR Pharma. We believe that the U.S. market for Steriod-refractory acute GVHD is likely to be 10 times larger than it is in Japan. And so given our increased royalties in the last 12 months on products sold in Japan has provided very good line of sight for how this product would be adopted if approved in the U.S. Please go to the next slide, please. Slide 12 shows the totality of the data that supports the clinical outcomes with Remestemcel in children with steroid-refractory Acute Graft versus Host Disease. The product is being evaluated in three different clinical programs. Highlighted in yellow in this table are the outcomes by Day 28 response in the first row and by day 100 survival in the second row across each of these three trials. And what you see is a very high consistency in survival in patients who received Remestemcel between 66% and 79% across these three programs. And in contrast, what you see on the left hand side is a substantial lower survival in comparative control groups. A placebo -- a group that got a placebo, randomized control trial against Remestemcel had a 54% survival. And the most recent comparator group, the MAGIC cohort, treated with the best available therapy demonstrated a 57% survival. So we're very pleased by these results. And they support the dataset that was part of the BLA that went to the FDA. Please go to the next slide please. More recent data published in bone marrow transplantation last year in a controlled trial performed by lead investigators at Mount Sinai Hospital in New York, showed that when children from our Phase 3 program were matched by disease severity with control patients receiving the best available care, the day 28 response levels in those with MAP scores above 0.29, a validated biomarker of high risk patient population demonstrated a significant benefit in both day 28 response and Remestemcel treated patients on the left, 67% versus 10%. And on the right hand side, this benefit was also seen more significantly in survival, where 64% versus 10% survival benefit in Remestemcel treated patients versus controls. Go to next slide please. So what is our plan for the BLA resubmission for Steroid-refractory Graft versus Host Disease? In response to questions raised by the FDA, we have evaluated our potency assays that were in place and that were prospectively analyzed against clinical outcomes at the time of the Phase 3 trial. And we believe that the key potent test measuring T-cell activation helps establish a clear relationship between potency and survival based on the Phase 3 trial outcomes, and helps establish a clear understanding of the mechanism of action by which Remestemcel improves GVHD outcomes in particular survival, since we understand that T-cells are the basis of the disease itself. Additionally we've generated data from the expanded access program, EAP 275 that followed 241 children over more than 10 years, who -- where Remestemcel was used as salvage therapy. And in that program, the existing potency assay targeting T cells demonstrating how Remestemcel targets T cell activation has shown that changes in manufacturing, which resulted in enhanced bio activity of the product could be predicted by the assay as could improvements in outcomes, notably survival. So these new data will all be part of the BLA that's submitted, resubmitted to the FDA. And we expect to complete that by the end of this quarter. In addition, during the quarter, we performed a mock inspection, pre-approval inspection of our GMP manufacturing facility in Singapore. And we were pleased with the outcome of that, comprising both the site and virtual inspections by external auditors. Since the inspection of the site is one of the outstanding items as part of the BLA resubmission. All of these new data will be provided to the FDA, primarily addressing the CMC, outstanding items as requested in the CRL response. And the additional new clinical data will form part of the resubmission. If accepted CBER will consider the adequacy of the totality of the clinical data and the enhancement to their potency assays in the context of the data as part of the resubmission outcomes. Next slide, please. Now let's move to the next program, which is the follow-on for Remestemcel, the use of Remestemcel an anti-inflammatory agent for acute respiratory distress syndrome due to COVID-19. We've completed the first study in about 220 patients where the strong signal of efficacy was observed in an exploratory subset of patients who were on Dexamethasone, and were under the age of 65. And as you can see here, on the left hand side, there's a survival curve in these 73 patients. You can see a hazard ratio of 0.23 in terms of a significant reduction in mortality through 90 days. And you can see on the right hand side that in terms of secondary endpoints of improved respiratory function significantly was seen through day 14 and 21 and day 30 in those who received Remestemcel in combination with Dexamethasone. So on the basis of these data, we've entered into a Memorandum of Understanding with Vanderbilt University Medical Center, next slide, please, a coordinating body, working together with 40 sites across the United States that focuses on studying ARDS and other critical illnesses. And we will be working with Vanderbilt over the next few months to establish and design a collaborative study focusing on the younger patients at high risk of mortality to develop a protocol that we will then take to the FDA for their review and agreement to move forward into a pivotal trial design that potentially could support an emergency use authorization. Let's move on to Slide 17, please. Now looking at our second technology platform, Rexlemestrocel, immuno-selected cells, developing allogeneic therapeutics for direct injection into sites of severe inflammation. Here we are focusing on chronic low back pain due to degenerative disc disease. This is an extremely high unmet need that affects over a million people in the U.S. and a similar number across the E.U.5. And we're talking about patients who have anatomic abnormalities with progressive degeneration of the disc. And these are often times people in the 40s and 50s, fairly young people whose quality of life is severely affected. And as a result of the degeneration of the disk there's substantial secondary inflammation, and that inflammation that results in severe pain, unremitting pain, that is not responsive to typical conservative measures, including non-steroidal drugs. And ultimately, it's the number one cause for prescription opioid usage. 50% of opioid prescriptions are for chronic low back pain due to degenerative disc disease. So we will understand the complications of chronic opioid use including overdosing, etc. And so this is a major area of focus for us, for government, for reimbursement agencies, ultimately for FDA. Next slide please. This slide 18 shows the patient treatment journey as exists today, for patients with chronic low back pain from degenerative disc disease, and where we think Rexlemestrocel could actually fit and make a difference. And as you can see here after conservative treatments, really opioid analgesics that are the most widely used. And then moving on from that is interventional therapies, including epidural steroid injections that are off-label, not approved for this indication, and a variety of interventions such as spinal cord stimulation and radio frequency ablation. Ultimately, a few percent of these patients go on to have surgery that require spinal fusion disc replacement. But really what the objective here is to intervene as early as possible, within months to a year or so after conservative treatments have failed and before opioid analgesics or other interventions. And in fact, if we go to slide number 19, that's exactly where we saw the maximum treatment benefit in our recently completed Phase 3 trial. This is a snapshot of the subgroup of patients that were treated within the first five years of pain, and which is the -- which was the median duration of patients in this study. And whilst we achieved reduction in pain, significant reduction in pain in all 400 patients, in the Phase 3 trial, the greatest reduction in pain was seen in those who were treated within the first five years. And you can see here, the outcomes by mean change in pain over up to 36 months. In green, the placebo group; in blue, those patients who were treated with cells alone; and in red, those patients who were treated cells plus hyaluronic acid. In an earlier Phase 2 study, we demonstrated the hyaluronic acid by itself did not have properties that by itself improved pain over and above placebo. However, in combination our cells with the carrier, Ha, seemed to have a synergistic benefit. And there's a scientific rationale for why that's the case and why in fact the two were used together in our Phase 3 program. But what you can see is that when cells, with the Ha carriers were used, we see roughly a -- approximately a 20 point improvement as early as 12 months relative to controls in green, and these slides show mean change in pain with 95% confidence intervals around them. Highly significant reductions in pain at 12 months, 18 months, 24 months and 36 months, at every time point study between cells with ha versus saline injection into the disk. Just to put into context, the use of opioids gives you roughly a reduction in pain that is similar to what we've seen in this study with saline placebo control. So the 20 point or more improvement in pain on a VAS score from -- where -- of zero to 100, where the entry point was an average of about 70, represents quite a stunning improvement in pain that is clearly durable from a single intervention of our cells. And this will form the patient population that will be studied in a confirmatory study that we expect to commence by the end of this year. We go to the next slide, please. This slide is a snapshot of market access and pricing insights of various agents that are used in the U.S. for pain, for back pain. And on the left hand side, you see this sort of range of various nonsteroidal anti-inflammatory drugs or opioids. But what you see on the right is the significant increase in pricing and reimbursement for biologic agents, including anti-TNF agents that are used in some inflammatory disease patients with back pain. So these guides to where we see the commercial opportunity that we believe that our product should achieve in the upcoming trial, significant reduction in pain and in secondary endpoint of function will obviously fit into this paradigm. If we can go to the next slide, please. So we're preparing now for the next Phase 3 trial in chronic low back pain. We have alignment with the FDA's OTAT office on the primary endpoint, which is what I just showed you, mean pain reduction over 12 months, with secondary endpoints showing improvement in function and quality of life measures, as well as potential reduction in opioid use, because we've demonstrated that to be the case in the previous trial. The objective is to show durable reduction in pain, and position Rexlemestrocel as a potential opioid sparing agent. In addition, because of our partnership with -- in Europe, we have an agreement to include at least 20% of the subjects in this trial, to be enrolled in the EU to support submissions, not just to the FDA but to support submissions for approval to EMA. And active discussion are now ongoing with our key investigators and advisors, in order to complete the final protocol design and submit for clearance by the FDA. Moving along to slide 22, this is our final major program, chronic heart failure in patients with low ejection fraction. This continues to be a major cause of mortality in Western countries. More than 6.5 million people suffer in the U.S. with chronic heart failure. Mortality approaches 50% at five years and mortality from heart failure due to low ejection fraction in particular remains a major problem that existing and new drugs have not addressed adequately. So there are a number of new drugs that have been approved that predominantly volume reducing agents and they impact symptomatic heart failure, shortness of breath and hospitalizations from volume overload and shortness of breath, but do not have a major impact on the major adverse cardiac events of, of cardiovascular mortality, heart attacks or strokes. And that's where we think that Rexlemestrocel has a unique opportunity to create its own space. Next slide, please. This is the patient treatment journey today. For chronic heart failure, and where we think that Rexlemestrocel can make an impact. As you can see in early stage disease on the left, class I, class II, a variety of pharmacologic drugs are used to improve symptomatic heart failure. Newer drugs, including the Entresto drug, including SGLT2 inhibitors are now approved for class II/III patients again for symptomatic improvement, predominantly reducing volume related symptoms. However, we think that our product, Rexlemestrocel as a single intervention can be used in combination with any of these agents in patients with class II/III or IV disease, even in patients on LVAD, for which we've got an RMAT designation, because the general mechanism of action of our cells is to increase left ventricular systolic function, which then has an impact on longer term, major cardiac event outcomes. Next slide, please, Slide 24. Recently, we announced that in fact, from the phase 3 trial, 560 patients with so called Dream heart failure trial, we observed that in all treated patients 537 patients, a single injection of Rexlemestrocel resulting in 52% greater increase in systolic functional recovery as measured by injection fraction from based on the 12 months compared with controls. In absolute terms, we saw a five point improvement in ejection fraction versus 3.3 improvement in controls when they both started at roughly similar numbers of 28.7 and 28.6. Even more strikingly, the entire treatment benefit was in patients with evidence of inflammation at baseline, as measured by positive CRP. And in the 301 patients who had elevated CRP levels, we saw an 86% increase in ejection fraction at 12 months from Rexlemestrocel injection compared with control saline. And here we see that the absolute change was 5.6 points at 12 months versus 2.9 for the controls, which was very meaningful, we think biologically. And in fact, in following up patients long term these changes in ejection fraction early are highly predictive of reduction in long term MACE events, as you can see in the next slide, slide 25. On the left hand side, we look at all three of the patients, 537 patients and we see that the Rexlemestrocel group showed a 33% reduction over a mean 3 period of follow up in the three point MACE of cardiovascular death, non-fatal MI and non-fatal stroke versus control. But if you really look at the figure on the right that [ph] is amplified in patients with baseline inflammation as measured by CRP levels above two. And here you can see that in this group, patients Rexlemestrocel reduced the three point MACE event outcome by 45% over a three year period of follow up. So conclusion is that early improvement in systolic function as measured by ejection fraction, is highly predictive of subsequent reduction in MACE outcomes. And mechanistically, that make very much sense because if you can reduce the inflammation in the myocardium, in heart failure patients early, you protect the heart muscle cells, you improve their perfusion, you prevent their death, improve systolic function, and all of those should have a major impact on long term, major cardiac events including cardiovascular death. So if we move to the final slide, these are our major clinical and regulatory milestones for the next 12 months and they are substantial. For Remestemcel, as I've mentioned earlier, FDA filing for the BLA for the resubmission of our BLA is expected this quarter. It's a major event for the company. And if accepted FDA approval would be planned six months after filing with a potential launch in Q1 2023. In addition to that, we're working with Vanderbilt University to build a trial protocol that would go to the FDA to confirm the previously observed reduction in mortality COVID-19 ARDS patients. Finally, with Rexlemestrocel, we're particularly excited about the A, commencement of a pivotal trial in back pain, to reduce pain with a 12 month primary endpoint. And B, for our upcoming proposed meeting with the FDA to discuss under the unmet designation, a common mechanism of action in patients with inflammatory heart failure, both class II, III and IV with LVAD, and the potential pathway towards approval. I'll leave it at that. Thank you very much. And we're open to questions.

Thank you [Operator Instructions]. The first question today comes from Louise Chen from Cantor Fitzgerald. Please go ahead.

Hi, team. This is Wayne for Louise. Congrats on the progress this quarter. And thank you for taking our questions. So we would like to ask what are the current survival outcomes in acute GVHD and how does MESO view the unmet need? Thank you.

Thank you very much. That's a very, very important question. I think it's clear to see in various publications, that over the past two decades, survival outcomes in steroid refractory, acute GVHD have not materially changed. And that's despite many different approaches, therapeutically, prophylactically. Once you don't respond to steroids, the likelihood of death from steroid refractory disease is very high. And in particular, in the most severe patients, those was great with grade C or D disease, or more recently, patients with a new validated biomarker, the so called MAP score above 0.29, which appears to be more sensitive to predicting disease severity than does grading by clinical scores, those kinds of thresholds are highly predictive of severe mortality. Patients with severe disease have survivals that are very dismal in the order of about 20% despite all the various therapeutic approaches that have been tried. In particular, the only drug that's been approved to-date for GVHD is Ruxolitinib. And it was approved on the basis of a single open arm study, when it subsequently did a randomized control trial as it was required to do it in a post-approval commitment. There was no survival benefit in Steroid-Refractory GVHD disease. So the unmet need continues to be there, particularly for the more severe cases with GVHD, and we have shown high survival rates across multiple studies of Remestemcel in children. We have more recently or our collaborators more recently, independent investigators more recently published a significant survival benefit, with Remestemcel in children with the highest risk for mortality, where mortality in the controls -- survival controls was of the order of 10% and survival in Remestemcel treated children was of the order of 64%. And so I think what we're seeing here now is the ability of a very potent immunomodulatory therapeutic Remestemcel to impact on survival outcomes in those children who have the greatest levels of inflammation and the greatest risk for mortality. And the unmet need continues to be in children, absolutely, because there are no drugs approved in children under 12 at all for this devastating disease. And in adults, with high degrees of inflammation, as such as those with high MAP scores, and continued high mortality, we think that's an obvious place where Remestemcel would be a potential treatment of choice.

Thank you. That's very helpful. Thank you.

Thank you [Operator Instructions]. The next question comes from Jason McCarthy from Maxim Group. Please go ahead.

Hey, guys. Thank you for taking the question. This is Michael Okunewitch on the line for Jason. So I guess my first question, I'd like to ask a bit about the strategy in heart failure, because you do have late stage data in two populations, the advanced and the LVAD patients. So could you kind of highlight how you're looking at the strategy for each population? And then what are the possible outcomes we could expect from your upcoming interactions with regulators?

Yeah, look, I think it's -- you don't want to be anticipating outcomes from upcoming FDA meetings until you've had them. You need to have those discussions in a fulsome way. But what has become quite evident to us is that the continuum of heart failure from class II through class IV, and even on LVAD the common thread is degree of inflammation in the myocardium. And the ability of Rexlemestrocel to respond to that inflammation by turning off the inflammatory stimulus and improving left ventricular systolic function. And you can measure systolic function several ways. You can measure it by ejection fraction, when you've got earlier stage disease. You can measure by the ability to come off a left ventricular assist device, so called weaning in patients who are dependent on a ventricle assist device. But I think that the message is that in the setting of inflammation Rexlemestrocel improves left ventricular systolic function. And depending on the target population, the longer term outcomes, the clinical outcomes, the consequence of poor ventricle, ventricular function are different and are impacted. And in the class II/III population improvement in systolic function at 12 months is associated with long term reduction in MACE events, cardiovascular death, heart attacks strokes. In the LVAD population, the ability to improve systolic function is associated with other outcomes, including GI bleeding, including hospitalizations, etc. And so I think the way to look at this is an underlying mechanism that is consistently seen with Rexlemestrocel in the setting of inflammation, and how to think about its potential use and approval in these particularly high risk patient populations. That's really the basis of the discussions with the agency.

Thank you. That's very helpful. I'd like to follow up and just ask a little bit about the chronic lower back pain program, and in particular, at what stage or time point following failure to manage on conservative management, are you looking for Rexlemestrocel to fit in? If I recall, surgery is generally considered within as little as six months. Would this be a similar timeframe given that patients qualifying for surgery? As we learn your KOL event [ph], their physicians may be particularly open to cell therapy as an alternative for these patients.

Yeah, I wouldn't look at this is an alternative surgery. I mean, the patients who are presenting with severe pain to the pain physicians don't necessarily have a surgical lesion that's amenable to fusion or disc replacement, which is really -- that we're talking about. We're not talking about discectomy is which are used for nerve root compression. We're talking about patients who don't have an over compression to have early stage, radiographic degeneration, but it's severe pain as a result of inflammation that occurs there. And those patients will go on for years really with opioids and other approaches before they seek surgery. So we're looking at patients early as opposed to late and your point is right. However, the sooner that they present with a diagnosis of discogenic back pain, the sooner they should get an injection of our cells. It's clear that the earlier the intervention, the more likely it is for the cells to have an effect in terms of turning off the inflammatory cascade, and resulting in a durable long term reduction in pain for as long as at least three years is always seen. So we will focus on average that access these [ph] patient as early as possible after diagnosis is made, so they're not suffering. They're not taking opioids, they are not focused on other interventions. And therefore, we should be very early in the patient journey.

Thank you. I appreciate you answering my questions.

Thank you. The next question comes from Edward Tenthoff from Piper Sandler. Please go ahead.

Great, thank you so much for taking my question. And it really looks like a pretty exciting period coming up for the company. So I just wanted to sort of how partnering fits into your go forward strategy. And I know, you guys have been successful in the past. And these are major block cluster indications, just to kind of articulate what is sort of the priority to keep and where do you think maybe a partnership may best help maximize the value, either with Remestemcel Rexlemestrocel? Thanks.

Yeah, that's a complex question. So I think with respect to Remestemcel, we see the value driver for this company as having a first product approved and launched in the U.S. market. And we're anticipating doing that ourselves. We've got a strong commercial team. Our COO is heading the commercial launch plans, building a targeted sales force, stage gated investment in sales, marketing and distribution network. But I think first part approval was getting through the regulatory framework as a first allogeneic cell therapy will be seen as a huge benchmark. And the reimbursement for that product, we think will be similar to some of the CAR-T products that are already out there given to similar target patient populations. I think it makes a lot of sense for us to focus on the first product delivery to commercialization on our own. There's potential obviously to unlock great value in that product in multiple additional indications, including ads, including other inflammatory conditions, both in children and adults. And I think post approval, we will be focusing on strategic partnerships for that product in various indications on a perhaps an indication by indication basis in areas that we would not have the commercialization panels available to us at this point in time. With respect to Rexlemestrocel, which is currently in like stage Phase 3 development, similar kind of considerations exist in that the market potential in blockbuster areas like inflammatory back pain or inflammatory heart failure, at large, will require commercial distribution channels that partners can bring to the table, that we wouldn't want to be in a position to invest in at this point in time. The question is more of timing, rather than it's more of timing is really the issue. And have alternative opportunities in front of us in terms of have access to capital to complete some of these studies that not require strategic partners to be involved with until, again, approval is close at hand. So I think the strategies for commercial partnerships in late stage will be different than the way we would look at things if we were earlier in in Phase 1 or Phase 2, for example. And they are different for an approved product, which has a follow on series of indications than for products that is about to complete a pivotal Phase 3, if that makes -- does that makes sense?

It makes a lot of sense. Thank you very much Silviu.

Thanks.

Thank you. At this time, we're showing no further questions. I'll hand the conference back to Dr. Itescu for any closing remarks. End of Q&A:

Well, before we close, I'd like Dr. Rose to give his view on the exciting prospects in front of us with products like Rexlemestrocel for back pain. Eric, would you like to just give your view on how you see that as a potential value driver for the company beyond our GVHD asset?

Sure. Obviously it's a point of entry into a very large marketplace. And we think the data that are there in randomized trials already show a very substantial benefit to patients with pain duration relief, duration of relief, that is years as opposed to months which is all that's been achieved with previous pain medicines using the standard for FDA trials that has been pursued for pain in general and back pain due to herniated discs in particular. Let me go back though to GVHD. To say that we're not excited about this would be the understatement, I think, of the century. We're very excited about GVHD because one, it's a lethal disease. Two, the quality adjusted life years that can be added to the life of the beneficiary of our therapy is substantial. And three, the market has shown that even orphan drugs in this space, command considerable value in the marketplace. They are drugs that have been improved recently without randomized trials in general, for these indications, for the indication of chronic GVHD, which is essentially an extension of acute GVHD with now two companies, I believe that have achieved more than $1 billion valuations with that indication. We think we're going to be right in that range as a company in terms of our value, and in terms of benefit that we provide to patients. This is a whole new class of therapeutics. There is no off-the-shelf, stem cell, or any cell product, as far as I know, aside from blood transfusions that's approved by the FDA for therapeutic use. And the company stands at the precipice of a breakthrough in this regard for a class of therapeutics that I think will have wide usage in multiple diseases. And we believe that it will be appropriately valued for that as well, once GVHD is hopefully approved. So let me stop there.

That's very insightful. Thanks, Eric. Really appreciate those comments. Sure, and on that note, I want to thank everybody for participating on today's call. We're very excited. I think this is going to be a transformative year for the company. And we look forward to updating everybody in short order on our upcoming milestones. Thank you, everybody.

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