Morning, John. Of course. Of course, Mesoblast is the global leader in allogeneic cellular medicines for inflammatory disease, and it has been a huge year for the company. Twelve months ago, we sat here, Paul, sweating on an FDA approval. Of course, that came out a few days before Christmas, and you've managed to make every post a winner since then. It's been a huge year. Yeah, it seems like a long time ago, John. Yeah, what's happened? I think we've been busier than ever once we got the approval, so there was no rest. Yeah, indeed. Now, for everyone's benefit, Silviu is going to join us momentarily, but we're pressing on for the moment. A couple of days ago, the company announced the appointment of Jim O'Brien as the CFO. Welcome, Jim. Thank you for joining us this morning. John, thank you very much as well. I'm joining you this morning from Melbourne. Good on you. I'm here with the team locally. Yeah, good. I'm excited to be here. Jim, just give us a bit of an overview of your career and why you were so excited to join Mesoblast. Yeah, happy to do so. I'm a traditionally trained accountant through PricewaterhouseCoopers for nearly a decade, and it's been about 25 years now in the pharmaceutical, life science, and biotech industries, working for large public companies. Mesoblast is a company that is on the cusp of some really great things following the approval earlier this year. As a commercial organization, I'm here to help drive the growth of the company, as well as to make sure that we can deliver on all of the commitments we're making to Wall Street to make sure that the value of the company is realized. I'm excited to be here during this pivotal time for the company's growth. Jim, you've worked for some of the big pharma companies over the course of your career. I have. I started at Bristol Myers Squibb and worked my way up through. I was with a company called Actavis before its transformation into what it is today as part of the AbbVie Group in the U.S. Along the way, we've done many public offerings and raised capital and straightened balance sheets for a number of big companies, and I'm looking forward to doing the same here at Mesoblast. Yeah, it's going to be exciting right over the next couple of years. Now, Paul, recently, the company announced an upcoming meeting with the FDA to talk about your back pain product for chronic back pain. Sorry, your back pain product. Tell us about the background of that meeting and what you hope to achieve for it, because this is going to be quite a pivotal meeting for the future of Revascor. Yeah, so I mean, obviously, first of all, we have the ongoing inflammatory Phase III trial. That’s enrolling extremely well. It’s a 300-patient randomized trial that we will be planning to go through a traditional approval route to FDA once that trial reads out in 2027. We expect one year of follow-up, so we expect to be finished enrollment sometime during the first quarter next calendar year, so 2026, by March. In the meantime, we’re heading back to FDA. As you know, we have an RMAT designation for that product, which is like a breakthrough designation. The FDA recently released guidance to industry, draft guidance to industry in September, and this is coming from the top down, I would say, from the administration, where there’s still a large focus in the US on the opioid crisis. They talk about the number of deaths that are still occurring as a result of overdosing opioids. They know that one of the biggest drivers of prescription opioids is actually chronic low back pain, the indication that we're seeking to treat. They are calling on industry to have solutions, non-opioid solutions for chronic pain, which is exactly what we're targeting. We are going in to have a chat to show them data that we have from the first Phase III trial in 400 patients on the effects on patients that were taking opioids. In that trial, there were actually 168 patients, so around 40% of the trial, people were taking or patients were taking opioids at baseline. We have some data that shows that after a three-year period of follow-up, despite patients being told not to change their medicine, three times the number of patients that were taking our drug came off opioids versus controls, and it was significant. We are going into chat to them and to show them that data, and I guess we will have a discussion around what they think about that and pathways that we could help the FDA and the administration with their quest to reduce the opioid crisis. That all sounds encouraging. Do you expect any amendment to the trial protocol or an early termination of the trial as a result of this meeting? No, no, we're not seeking to do that, John. I think that that trial is, as I said, enrolling very well, and we expect to complete enrollment by the end of next quarter. This is potentially another avenue or pathway, particularly targeting patients that are taking opioids and are trying to reduce their opioids. I want to drill down on a couple of aspects of the chronic bowel back pain trial, the trial that's enrolling at the moment. How are you measuring pain? Because obviously, in pain trials, the key risk is the placebo risk, the risk that the group on placebo outperforms. Tell us a little bit more about how you're measuring pain. Is it daily, weekly, or monthly, and so on? Yeah, so the patients have electronic diaries, which they complete. This will be different from the first trial of modern technology, and they're sort of measuring their pain through what they call a VAS score, Visual Analog Score, on a sort of weekly basis. That data is all collated over the 12-month period of follow-up. You're right in saying that placebo in pain trials is a challenge. We obviously have the we've done a couple of control trials now, and the first trial showed a substantial benefit in pain reduction versus placebo. I think we already have that hurdle covered. Secondly, and interestingly, what the FDA allowed us to do in this second trial is that we actually are using in the first trial, we were using a saline injection into the disc, which actually had some benefit of hydration of the disc, etc. It was not just purely a placebo. In this second trial, the FDA has said for us to do basically what they call a sham injection. The injection is next to the disc for the controls, which we think further de-risked that placebo or control effect. That was an excellent concession from FDA for us in that trial. Finish off on this one. Mapping out the timeframe now. Enrollment of completion of enrollment in the first quarter of calendar year 2026. The endpoint is 12 months from the last patient enrolled. That takes us to the first quarter of calendar year 2027, a few months to compile data. We could be looking at headline data, you would think, in maybe May, June, July, calendar year 2027. First half of 2027. Yeah. Yes, first half of 2027. The product's got an RMAT designation. Filings with FDA will be eligible for fast- track reviews and things like that. Manufacturing, where are you with that? Who's the manufacturer? Who looks after all the CMC? Right. Yeah, so we're manufacturing. As you know, we manufacture on a couple of sites in the U.S. and also through Lonza in Singapore. We're currently ramping up the commercial manufacturing as part of, really, as part of the cardiac program, but it's relevant for the back pain program as well. So that's Rexlemestrocel-L. And so we're ramping up that. It'll be U.S.-based manufacturing. We're putting in place commercial runs and things like that. We're going to be well and truly ready for the time back pain launches as we're doing all the work for the potential filing on the BLA for accelerated approval in cardiac. It's a little bit of a confusing message there, but basically, the commercial manufacturing will be well and truly established by the time the back- pain product launches. Yeah, excellent. All right, that's been a good run-through. Silviu has now joined us. Welcome, Silviu. Thanks for coming on. Thanks for having me. Had some difficulty getting in, but that's okay. That's all right. That's right. We've just spoken to Jim. We've talked about the back- pain trial. Silviu, let's just talk about Ryoncil. Just mentioning earlier to Paul, 12 months ago, we were sitting here sweating on an approval. It's been a wonderful period since then with the approval coming in December last year, and it's been every post a winner since then. Revenues for the September quarter are about $22 million. Can you take a moment now to just run through your understanding or your view of how commercialization has proceeded and what we can expect over the course of the next 12 months as commercialization really ramps up? Yeah, look, I guess when we launched after post-approval in January, there were a lot of unknowns. I would say that we've clearly taken all of the unknowns off the table. By that, I mean we didn't know how we would price it, whether the pricing was going to be acceptable, whether the insurance companies, both commercial, Medicare, Medicaid, were going to be in agreement with the pricing and reimbursement, and what the adoption would look like. I would say all of those have gone exceptionally well, much better than we had dared hope. Certainly, the street was unclear. The way I see it, we've got over 45 or so sites already onboarded. All the major transplant centers have onboarded us, and a lot of them have our product on their formulary. We've got all the commercial insurers covering us. We have federal and state Medicaid coverage, mandatory Medicaid coverage. We have a J code that federal Medicare has put on our product at a 6% premium to the price that we had asked for. We clearly have substantial adoption and use of the product. In fact, many of the hospitals that have used it once are now repeat customers. Our best customers are the ones that have used the product in their first trial, and they come back a second and a third time. I think we have surprised ourselves, actually. I think most importantly, for a first-in-class, brand new product that previously had never been launched for any indication, having the first and only approved stem cell product in the US with reimbursement that does not require any step-throughs or any discounts is a terrific outcome. First quarter post-launch, I think we had about $13 million in gross income with about a 14.5% gross- to- net. Second quarter of our launch product was around $22 million-$23 million with a lower gross- to- net, about 12%. I would expect in this quarter, we're going to outperform yet again. Yeah. That J- code, just to put some meat on the bones there, that's a really important de-risking factor for new hospitals. Just tell us a little bit more about that in a couple of sentences. Look, you know hospitals that are dependent on Medicare, Medicaid coverage have a risk when there's a high-priced product that they're expected to pay upfront for and hope that they're going to get reimbursed later. Having a J- code means that federal Medicaid has mandated that that is the price at which every state should be reimbursing the hospitals at. Now, Tennessee or Oklahoma or various states will have specific contracts with their hospitals, some sort of discount to the J- code or some such thing. That's already well understood. Having a J- code that says, "This is the price that we're working off," gives the hospital certainty they know exactly what they're going to be reimbursed. That opens the ability for 50% of kids who are on Medicare to have the product with certainty. Yeah, yeah, that's key. You have talked in the past about unbelievable levels of bureaucracy, even at the hospital level, in order to get adoption moving for drugs. How does this J- code change things for things like high-priced drug committees, which exist at the hospital level? It's exactly what I'm saying. It's the certainty fact. When a hospital has a high-priced product, and our product is high-priced, it's $200,000 or so per infusion, and the kids have to have at least eight infusions, sometimes 12 infusions. That's a high price. 50% of the kids are covered by Medicaid. A high-priced committee looks to the guidance of Medicaid for certainty when they want to approve a product when they put it on a formulary. That makes the whole process take the whole burden away from the hospital and the uncertainty away from the hospital so that they're comfortable with approving kids once they're being enrolled. That's exactly what we're seeing right now. Excellent. Okay. Let's move on and talk about the label expansion for Ryoncil. We've talked about the adult program, and there's also Crohn's and other inflammatory diseases. What's your update there on those programs now? Look, we're working with the NIH in terms of the adult bone marrow transplant program with the organization called BMT-CTN, Clinical Trial Network. That's an NIH-funded body. That was shut down for the better part of two to three months. That has taken a little bit of a delay, but it's up and running and will be contracted this quarter to get that whole program started. It's been approved. The NIH has allocated funds for it, and that's public information. We expect that this trial commences later this quarter and hopefully first patient in early in the new year. That program aims to it's a randomized controlled trial, combining ourselves with the only FDA- approved product, which is Jakafi, in the U.S. in patients with severe disease. 50% of the adult patients have severe disease, gut disease. The poor response to Jakafi alone with a high mortality rate, and we think by adding ourselves, we'll make a significant impact on response and ultimately survival, which will mean that we should be able to maintain our premium pricing in adults. Yeah. Just quickly, what was the strategy behind going with the combination study as opposed to a head-to-head? It is not a question of head-to-head. If the product is already approved, you cannot have a control arm that does not take the approved product. The approved product is the control, and we are looking to better the outcomes on top of the approved product. If in the control arm, the approved product gets you 50%, we would expect to get 80%, for example, when you add ourselves on top of the approved product. The point of that strategy is that we close completely the loop in second line. As soon as someone fails steroids, this would be the only treatment available to them, Jakafi plus ourselves. There is no wiggle room for any other drug to come in between us and Jakafi. It is the right strategy. It allows us to get into a market that is three times bigger than the pediatric market. It'll take about a 12-month period to enroll, and the primary endpoint is day 28, a very short primary endpoint. Yeah. Silviu, what has been the experience of physicians wanting to use Ryoncil in adults to this point? You'd be surprised how many requests we have for adult use, exactly in that patient population, patients who failed Jakafi and have got gut, liver disease. We now have a precedent where we've had at least one patient that's been approved and reimbursed by the insurance companies for that exact indication. Really? Okay. Okay. Really? Okay. Okay. Really? Okay. Okay. There's tremendous precedent suddenly. We have started by making the product available under compassionate care for these adults, and the results have been terrific. We have seen patients with liver disease going to complete remission when that failed everything else. The physicians are using it, and we have now had examples of insurance companies reimbursing it. Fingers crossed, things are moving well, even in the adult. Yeah. That is a breakthrough moment. I mean, reimbursement for off-label use is a big deal. It was really dependent on how passionate the physician is in staking his claim and making his case to Medicare, Medicaid. Actually, Medicaid California, which is actually the hardest nut to crack, was approved this off-label use in adults, understanding the way that the technology is working and the results have been seen. Just quickly, what about in Crohn's disease and ulcerative colitis? That's a mouthful. What's your progress there? There's a big unmet need in severe ulcerative colitis or inflammatory colitis, combination of both ulcerative colitis and Crohn's disease, but involving the colon with severe bleeding and risk for colectomy. There's a big unmet need. That's where we've had a previous pilot data. We had very nice results, and we're in the midst of putting together a randomized controlled study that would be both in adults and children for potential pivotal approval and label extension. There's a big unmet need in this space. Okay. Over the course of the next few weeks, you're moving very rapidly towards, obviously, the end of the year, but that is also the timeframe for the launchment of the BLA for the heart failure product. Look, that's going to be a big moment for the company as well, moving forward into calendar year 2026. How has that program been progressing? As Paul alluded, the main workload is on getting commercial manufacturing for the Rexlemestrocel-L product in place, scale-up potency assays, and having a site ready for potential inspection. All that work underpins both the cardiac BLA filing and the back- pain BLA itself. Probably that's happening probably an extra couple of months to have all ready for a BLA filing. Okay. Okay. That'll be most likely early in the new year based on that sort of expectation. Okay. Nevertheless, the opportunity in heart failure is enormous. The initial indication, you're going to go for an accelerated approval after you launch the BLA. That'll be in patients with an LVAD. Tell us a little bit about that market. You know the heart failure market that we're targeting, which is patients with ischemia and inflammation, is about 1 million patients prevalent across the U.S. It is a large market, large substantial market. Ultimately, we will have to do a confirmatory study in that population. The LVAD population is probably around 2,500 patients a year. It is much smaller. That is an entry point. It is an entry point into an ultra-orphan indication whilst we're then generating a confirmatory study in a much larger market. It allows you to get approval to price it, to launch it, and have physicians being comfortable with that product. What is important here is, as Paul said, it is one product for both inflammatory heart disease and inflammatory back pain. I think irrespective of which is approved first, the product will be available for multiple applications and indications. I think one of the main discussion points that we're having with the agency coming up in December is the potential to use this product for opioid cessation, yet another focus of the back- pain and the musculoskeletal areas for the product. As you know, opioid abuse continues to be a major problem in the U.S., a major focus for the administration. There's about up to 100,000 people die every year in the U.S. due to accidental opioid overdose. 50% of opioid prescriptions in the U.S. are for musculoskeletal disease, back pain, and osteoarthritis of the knee. The recent guidance from the FDA in September, a couple of months ago, was to encourage developers of non-opioid drugs like us to develop the drugs, broadly speaking, for musculoskeletal diseases for opioid avoidance, opioid cessation. I think that's an important discussion that we're going to have in a couple of weeks' time. Yeah. We'll look forward to an update following that meeting. It's not going to change the back pain trial that you've got at the moment. It won't necessarily, but it may influence the heart failure trial, the confirmatory trial. All that remains to be seen for next year, I suppose. Exactly. Okay. We're just about out of time, but just a quick wrap, the priorities for calendar year 2026, two or three bullet points. Revenue growth, expansion into adults with bone marrow transplant beyond pediatric, initiation of inflammatory bowel disease, adult study, focusing on FDA filing for accelerated approval and completion of the adult back- pain trial. Yeah. Just one or two things to take your attention. It's a massive program. Thank you all very much for your time. Thank you, Silviu. Thank you, Jim. Thank you, Paul. It's been a really good update. We look forward to catching up with you again in the not too distant future. We're going to take a short break, and we'll be back.