Half Year 2025 Mesoblast Ltd Earnings Call
Excuse me.
Andrew: Virtual officer, and Andrew <unk>, our interim Chief Financial Officer.
Andrew: Today, we are presenting our financial results and operational update for the half year ended December 31 2024.
Speaker Change: We could.
Andrew: Go to.
Andrew: Slide four please.
Andrew: Mesoblast is the global leader in allogeneic cellular medicines for inflammatory diseases.
Andrew: We have one product already FDA approved <unk>.
Andrew: We have multiple locations globally were listed jewelry on the ASX in Nasdaq.
Okay.
Okay.
Andrew: We have.
Okay.
Andrew: More than 1000 patents and patent applications.
Okay.
[music].
Andrew: Support our products.
Andrew: Beyond our first approved product right also we have.
Andrew: Two other major products in phase III, and we have a whole pipeline sitting behind these.
Andrew: We have a scalable manufacturing have been FDA inspected and we have a supply chain capability that allows us to meet the.
Andrew: Global needs commercially.
Next slide please.
Andrew: Our platform technology is based on a shared mechanism of action across all of our products.
Andrew: Zinc cobalt lineage precursor stromal cells.
Our highly purified.
Andrew: Barry.
Andrew: Concentrations.
Andrew: And final crop preserves vials. These cells have on this surface range of receptors for inflammatory cytokines, including interferon Gamma TNF IL 17, IL, six and a one and others and when the cells.
Andrew: In regions of severe inflammation, where the cytokines play major disease roles. They are able to respond to inflammation with the release of multiple anti inflammatory factors that act in concert to turn off the damaging inflammation that results in severe diseases and potentially life threatening out.
Andrew: Comes next.
Andrew: Next slide please.
Andrew: This slide provides a snapshot of our clinical product pipeline.
Andrew: Our platform technology based on Remy stem cell, our first generation product.
Speaker Change: My name is Ryan So has now been approved by the FDA.
Andrew: For the treatment of children with severe.
Andrew: Yes.
Andrew: Steroid refractory acute graft versus host disease.
Andrew: I'll be talking a lot more about this product, which today, we've announced pricing for.
Andrew: The physicians can access.
Andrew: The product is also being developed for adults with steroid refractory gvhd and will be developed.
Andrew: For life cycle extension into inflammatory bowel disease in both children and adults.
Andrew: Our second generation technology platform is termed rich, let me stroke. So these cells are immuno selected using monoclonal antibodies to high purity and potency.
Andrew: This technology is being developed for inflammatory cardiovascular disease and inflammatory back pain more about that later.
Andrew: Next slide please.
Andrew: Now I'd like to turn to Andrew <unk>, who is going to be discussing our financial results for the period ended December 31 2024.
Thanks, Sylvie turning to slide eight for the financial highlights for the year.
Andrew: Our cash balance at December 31, 2024 was 38 million U S dollars with pro forma cash of approximately $200 million.
Andrew: After the successful completion of our global private placement, which raised 161 million U S dollars.
Andrew: Net operating cash spend.
Andrew: It was $27 million U S dollars in the first half of FY 2025.
Andrew: Which was a 23% reduction from the first half of FY 2024.
Andrew: As a result of FDA approval of <unk> in December.
Andrew: $23 million.
Andrew: Provision against the value of inventory manufactured in expense in prior periods was reversed and is now recognized as an inventory asset on the balance sheet.
Andrew: Turning to the next slide you will see our P&L statement.
Andrew: BLA approval.
Andrew: Samba resulted in noncash balance sheet adjustments, including the write off of the value of inventory.
Andrew: Starting with the line items, most affected by the noncash balance sheet adjustments.
Andrew: Let's look at the results for both the reevaluation of contingent consideration and the revaluation of the warrant liability.
Yes.
Okay.
Okay.
Andrew: The increase in these line items in the current half year, where as a result of FDA approval.
Okay.
[music].
Andrew: We then contingent consideration on FDA approval the probability of success of pediatric Gvhd increased to 100% and resulted in a non cash re measurement, increasing by 4 million to $4 3 million U S dollars for half one FY 2025.
Andrew: Compared to <unk> 3 million for half one FY 2024.
Andrew: Within revaluation of warrant liability.
Andrew: As a result of FDA approval and the consequential share price appreciation.
Thank you for standing by and welcome to the Mesoblast coffee results for the period ended December 31st when you go needful.
Andrew: Our warrant remeasurement increased by $16 million to $12 million for half one FY 2025.
All participants in a listen only mode there'll be a presentation followed by a question and answer session.
Andrew: <unk> to a gain of $4 four.
Andrew: Half one FY 2024.
If you wish to ask a question you will need to press the star key followed by the number one on your telephone keypad.
Andrew: Within manufacturing as a result of the FDA approval.
Andrew: The $23 million in U S dollar provision against the value of inventory.
Dr. <unk>: I would now like to hand, the conference over to Dr. <unk>.
Speaker Change: Q do you think you could do.
Andrew: Manufactured in expense in prior periods was reversed.
Speaker Change: Please go ahead.
Andrew: And as a result, we are now recognizing $24 million of inventory on our balance sheet.
Speaker Change: Good morning, everybody I'm, Sylvia just skewed the chief executive of Mesoblast.
Speaker Change: Together with me this morning.
Andrew: The increase in expenditure for both our R&D and management and admin.
Marcellus Sentara: As Marcellus Sentara, Chief commercial officer, and Andrew <unk>, our interim Chief Financial Officer.
Andrew: It was due to non cash share based payments primarily for STI in lieu of cash based payments.
Marcellus Sentara: Today, we're presenting our financial results and operational update for the half year ended December 31 2024.
Andrew: But as described above the BLA approval resulted in a number of non cash balance sheet adjustments, which drove the loss after tax of 47 9 million U S dollars for the half year.
Marcellus Sentara: We could.
Marcellus Sentara: Go to.
Marcellus Sentara: Slide four please.
Marcellus Sentara: Visa blast is the global leader in allogeneic cellular medicines for inflammatory diseases.
Andrew: Pleasingly for the same half year period, our total operating cash flows were only 27 million in U S dollars, a reduction of $5 9 million and the comparative half year.
Speaker Change: We have one product already FDA approved right. So.
Speaker Change: We have multiple locations globally were listed Julie on the Asics and NASDAQ.
Andrew: Thanks for the call.
Andrew: Thanks, Andrew.
Andrew: We can go to slide.
Speaker Change: We have.
Andrew: Ken.
Speaker Change: More than 1000 patents and patent applications.
Andrew: I'd like to talk now about right on so.
Speaker Change: And support our products.
Speaker Change: Our launch strategy.
Speaker Change: Beyond that first approved product right on so we have.
Andrew: Pricing.
Andrew: Okay.
Speaker Change: Two other major product in phase III, and we have a whole pipeline sitting behind these.
Andrew: But also the first mesenchymal stromal cell therapy approved by the FDA.
Andrew: Next slide please.
Speaker Change: We have a scalable manufacturing have been FDA inspected and we have a supply chain capability that allows us to meet the globe global needs commercially.
Andrew: The first FDA approved off the shelf therapy for children, aged three months and older including adolescence and teenagers.
Speaker Change: Next slide please.
Andrew: With steroid refractory acute gvhd, a life threatening condition with high mortality rates.
Speaker Change: Our platform technology is based on a shared mechanism of action across all of that product.
Andrew: Next slide.
Speaker Change: Mesenchymal lineage precursor stromal cells.
Andrew: We have the opportunity to address.
Speaker Change: Highly purified.
Andrew: A very critical unmet need in children two months and older.
Speaker Change: Barry.
Speaker Change: Hi concentrations.
Andrew: Across the U S. Approximately 10000 allogeneic bone marrow transplants are performed annually.
Speaker Change: Final crop presents vials. These cells have on this surface range of receptors for inflammatory cytokines, including interferon Gamma TNF IL 17, IL six in one and others and when the cells are placed.
Andrew: Acute graft versus host disease occurs in about 50% of patients.
Andrew: Approximately half of these failed to respond to steroids.
But for those who felt the response to steroids mortality is very high and there are significant extended hospital stay costs.
Speaker Change: Placed in regions of severe inflammation, where these cytokines play major disease roles, they're able to respond the inflammation is the release of multiple anti inflammatory factors.
Andrew: We believe that the addressable market in the U S is approximately 375, new children per year with life, threatening steroid refractory acute graft versus host disease.
Speaker Change: In concert to turn up the damaging inflammation that results in severe diseases and potentially life threatening outcomes.
Andrew: Next slide please.
Speaker Change: Slide please.
Speaker Change: This slide provides a snapshot of our clinical product pipeline.
Andrew: In our phase III trial that underpin the FDA approval.
Andrew: <unk> also delivered high overall response rates at day, 28, which is a measure well established to predict long term survival in this disease.
Speaker Change: Our platform technology based on Remy stem cell that first generation product.
Speaker Change: Name is right on so has now been approved by the FDA.
Andrew: Overall response rates with 70% at day 28 significantly higher than is achievable with <unk>.
Speaker Change: The treatment of children with severe.
Speaker Change: Yeah.
Speaker Change: Steroid refractory acute graft versus host disease.
Andrew: Therapy for this disease.
Speaker Change: I'll be talking a lot more about this product.
Andrew: Importantly.
Speaker Change: Today, we've announced pricing for.
Andrew: 89% of the children enrolled in this trial had the most severe form of the disease, great CD, which involves the gastrointestinal tract and lever in addition to skin.
Speaker Change: And that physicians can access.
Speaker Change: Product is also being developed for adults with steroid refractory gvhd and will be developed.
Speaker Change: Well for life cycle extension, it seemed cemetery bowel disease in both children and adults.
Andrew: While also treatment was not discontinued or interrupted in any patient for any laboratory abnormality.
Speaker Change: Our second generation technology platform is termed rich, let me stroke. So he sells or immuno selected using monoclonal antibodies to high purity and potency.
Andrew: And the full course was completed without interruption in more than 85% of the patients.
Andrew: It's very different from the profile with other therapies used in these children with very severe disease as well as in adults with acute graft versus host disease.
Speaker Change: This technology is being developed for inflammatory cardiovascular disease and inflammatory back pain more about that later.
Andrew: Next slide please.
Speaker Change: Next slide please.
Andrew: Now the cost of treating children.
Speaker Change: Now I'd like to turn to Andrew Shepherd, now who's going to be discussing our financial results for the period ended December 31 2024.
Andrew: With steroid refractory Gvhd, who subsequently di is very high.
Andrew: The cost of bringing a child, who dies within 12 months of a transplant.
Andrew Shepherd: Thanks, Sylvie turning to slide eight for the financial highlights for the year.
Andrew: From steroid refractory Gvhd is approximately $2 5 million.
Andrew Shepherd: Our cash balance at December 31, 2024.
Andrew: And notably.
Andrew Shepherd: The 38 million U S dollars with pro forma cash of approximately 200 million U S dollars.
Andrew: It's $1 $8 million higher than four.
Andrew: Those children with steroid refractory gvhd, who actually remain alive.
Andrew Shepherd: After the successful completion of a LIBOR private placement, which raised 161 million U S dollars.
Andrew: Next slide please.
Andrew: <unk> has demonstrated long term survival free from acute gvhd.
Andrew Shepherd: Net operating cash spend.
Andrew: The long term follow up of brands sold by the center for International Blood and marrow transplant research CIB MTR.
Andrew Shepherd: It was 27 million U S dollars in the first half of FY 2025.
Andrew: And the 51 patients who were followed long term, notably 88% of whom had life threatening <unk> disease.
Andrew Shepherd: Which was a 22% reduction in the first half of FY 2024.
Andrew Shepherd: As a result of FDA approval for Ireland saw in December.
Andrew: <unk> survival was 51% and beyond that survival was relatively.
Andrew Shepherd: 23 million provision against the value of inventory manufactured in expense in prior periods was reversed and is now recognized as inventory asset on the balance sheet.
Andrew: Plateaued with four year survival of 49%.
Andrew: Notably only 14% seven children.
Andrew: Have died due to acute graft versus host disease through four years and beyond.
Andrew Shepherd: Turning to the next slide you'll see our P&L statement.
Andrew: One would have expected a much higher number to have died from acute gvhd is treated by other therapies.
Speaker Change: Dale I appraisal.
I'm Bob <unk>.
Speaker Change: <unk> had a noncash balance sheet adjustments, including the write off of the value of inventory.
Andrew: Next slide please.
Andrew: What is the value of brands so in treating pediatric patients with acute gvhd.
Speaker Change: Starting with the line items, most affected by the noncash balance sheet adjustments.
While the total benefits of patient outcomes using <unk> range between $3 2 million to $4 1 million.
Speaker Change: Let's look at the results by the revaluation of contingent consideration and the revaluation of the warrant liability.
Speaker Change: The increase in these line items in the current half year, where as a result of FDA approval.
Andrew: And this is based on health economic models for lifetime, Ultra rare disease and high impact short term therapies, including quality of life years gained.
Speaker Change: We didnt contingent consideration on this day appraisal the probability of success of pediatric Gvhd you trace.
Andrew: And the benefits comprise.
Speaker Change: Trace to 100% and resulted in a non cash re measurement, increasing by 4 million to $4 3 million U S dollars for half one FY 2025.
Andrew: Long term survival cost offsets and cost savings.
Andrew: Next slide please.
Yes.
Andrew: So for treating pediatric patients with.
Speaker Change: Compared to <unk> 3 million for half one FY 2024.
Andrew: Acute gvhd the recommended dosage around so.
Andrew: On our FDA approved label.
Speaker Change: Within revaluation of warrant liability as.
Andrew: Is.
Andrew: 2 million cells per kilogram body weight.
Speaker Change: As a result of SDI pringles and the consequential share price appreciation.
Andrew: Given intravenously twice per week for four consecutive weeks the wholesale acquisition cost.
Speaker Change: The warrant Remeasurement increased by 16 to 12 million U S dollars for half one FY 2025.
Andrew: <unk> is a 194000 per intravenous infusion across ore body weights.
Speaker Change: So again, a full point for our half one FY 2024.
Speaker Change: Within manufacturing as a result of the FDA approval.
Andrew: Next slide please.
Speaker Change: The 23 million in the U S dollar provision against the value of inventory manufactured in expense in prior periods was reversed.
Andrew: This is the mandatory hub that has been established terms my mesoblast.
It is set up to assist patients with insurance coverage financial assistance and access programs.
Speaker Change: And as a result, we are now recognizing 24 million U S dollars of inventory on our balance sheet.
Andrew: Ensuring that no patient has left behind in receiving this potentially life saving therapy.
Speaker Change: The increase in expenditure someplace out R&D and management and admin.
Andrew: Our comprehensive patient services hub.
Speaker Change: Susan.
Andrew: It provides access.
Speaker Change: Cash share based payments, primarily for STI in lieu of cash based payments.
Andrew: And helps both patients their families and institutions.
Speaker Change: So as described above the Baillie appraisal resulted in a number of noncash balance sheet adjustments, which drive the loss after tax of $47 9 million U S dollars for the half year.
Andrew: Next slide please.
Andrew: <unk> is.
Andrew: Is being made available for pediatric gvhd in the United States in.
Andrew: In March.
Speaker Change: Pleasingly for the same period at title operating cash flows for at least $90 7 million U S dollars, a reduction of $5 9 million and the comparative half year.
Andrew: We are we are.
Andrew: Approaching this.
Andrew: Staged stage manner.
Getting a transplant centers with highest volume and with established experience using the <unk> product.
Speaker Change: That's cool.
Speaker Change: Thanks, Andrew.
Andrew: Establishing and have established already a targeted sales force with experience in bone marrow transplant centers.
Speaker Change: We can go to slide.
Speaker Change: Tim.
Let's talk now about right on so.
Andrew: 15 of the highest volume centers account for 50% of patients.
Speaker Change: Our launch strategy.
Speaker Change: And the 45 highest volume centers account for 80% of patients and you'll hear more about this from Marcellus antara in the Q&A session.
Speaker Change: Pricing.
Speaker Change: Got it.
Speaker Change: But also the first mesenchymal stromal cell therapy approved by the FDA.
Speaker Change: Next slide please.
Speaker Change: Beyond acute gvhd, we have a strategy to expand the label and established lifecycle for the products.
Speaker Change: The first FDA approved off the shelf therapy for children, aged two months and older including adolescents and teenagers with.
Speaker Change: Our 'twenty one please.
Speaker Change: With steroid refractory acute gvhd.
In particular, we're focusing on inflammatory bowel disease inflammatory crohn's and ulcerative colitis.
Speaker Change: A life threatening condition.
Speaker Change: High mortality rates.
Speaker Change: Next slide.
Speaker Change: Pathology and the clinical aspects of these diseases are very similar to the inflammatory bell complications of acute graft versus host disease.
Speaker Change: We have the opportunity to address.
Speaker Change: A very critical unmet need in children two months and older.
Speaker Change: Across the U S. Approximately 10000 allogeneic bone marrow transplants are performed annually.
Speaker Change: And.
Speaker Change: The ability to respond to or I answer is similar and has been a value added in previous studies.
Speaker Change: Cute graft versus host disease occurs in about 50% of patients.
Speaker Change: The unmet need is large.
Speaker Change: Approximately half of these have to respond to steroids.
Speaker Change: In both adults and children.
Speaker Change: And for those who thought they were supposed to steroids mortality is very high and there are significant extended hospital stay costs.
Speaker Change: And in particular more than 60% of patients fell.
Speaker Change: The response was subsequently lose response to anti TNF agents, which are the first line.
Speaker Change: We believe that the addressable market in the U S.
Speaker Change: Biologics in this patient population.
Speaker Change: <unk> 375, new children.
Speaker Change: 25% of all inflammatory bowel disease patients.
Speaker Change: Here with life, threatening steroid refractory acute graft versus host disease.
Speaker Change: <unk> age and in these patients and anti TNF agents is the only approved therapy.
Speaker Change: Next slide please.
Speaker Change: In our phase III trial that underpin the FDA approval.
Speaker Change: This represents potentially as many as 7000 children.
Speaker Change: But I also delivered high overall response rates at day, 28, which is a major one.
Speaker Change: 50% to 60% of whom are.
Speaker Change: Well established to predict long term survival in this disease.
Speaker Change: Unlikely to be refractory to anti TNF therapies, and we're essentially right on so may have.
Speaker Change: Overall response rates with 70% at day 28 significantly higher than is achievable with others.
Speaker Change: May make a difference.
Speaker Change: Next slide please.
Speaker Change: The recent pilot study in adults demonstrating positive outcomes with ROI also.
Speaker Change: Therapy for this disease.
Speaker Change: Importantly.
Speaker Change: Directly injected submucosal layer in biologic refractory patients.
Speaker Change: 89% of the children enrolled in this trial had the most severe form of the disease, Great C D, which involves the gastrointestinal tract and Lila.
Speaker Change: Round so was.
Speaker Change: Delivered are direct in this coffee injection to areas of inflammation.
Speaker Change: Addition to skin.
Speaker Change: In addition, we have data showing that <unk> stem cell and juices early remission in Crohn's disease, adults, who filed a single anti TNF agents. Following the course of intravenous treatment.
Speaker Change: I also treatment was not discontinued or interrupted in any patient for any laboratory abnormality.
Speaker Change: And the full course was completed without any interruption in more than 85% of patients.
Speaker Change: Given the effectiveness of round, so treating children with.
Speaker Change: It is very different from the profile with other therapies used in these children with very severe disease as well as in adults with acute graft versus host disease.
Speaker Change: Guestroom.
Speaker Change: <unk> testimony related gvhd with inflammation of the gap and the existing data in adult chronic disease patients.
Speaker Change: We plan to further evaluate the immuno module three effects of rounds on Gi inflammation in medically refractory pediatric crohn's disease and <unk> patients.
Speaker Change: Next slide please.
Speaker Change: Now the cost of treating children.
Speaker Change: With steroid refractory Gvhd, who subsequently di is very high.
Speaker Change: Next slide please.
Speaker Change: The cost of bringing a child, who dies within 12 months of a transplant.
Speaker Change: In addition to inflammatory bowel disease, we have.
Speaker Change: From steroid refractory gvhd is approximately $2 $5 million.
Speaker Change: Our strategy to expand <unk> use in adult patients with gvhd.
Speaker Change: And notably its $1.8 million higher than for those children with steroid refractory gvhd, who actually remain alive.
Speaker Change: This continues to be an unmet needs, particularly in patients who fail <unk>. The only approved drug in adults with gvhd. This accounts for about.
Speaker Change: Next slide please.
Speaker Change: Well, Ryan So has demonstrated long term survival free from acute gvhd.
Speaker Change: 40% to 45% of all Russell <unk> treated patients. In addition survival of these patients with <unk> is very dismal.
Speaker Change: The long term follow up around so by the center for international Blood and marrow transplant research CIB MTR and.
Speaker Change: Around 20% to 30% by 100 days.
Speaker Change: And for this patient population there are no approved therapies treatment in a pilot study of third line agents.
Speaker Change: And the 51 patients who have followed long term, notably 88% of whom had life threatening <unk> disease.
Speaker Change: Using <unk> also demonstrated 73% survival at day 100.
Speaker Change: Survival was 51% and beyond that survival was relatively.
Speaker Change: And that provides us with the confidence to move forward into an appropriate.
Speaker Change: Plateaus with four year survival of 49%.
Speaker Change: Notably only 14% seven children.
Speaker Change: Pivotal study in adults.
Speaker Change: <unk>.
Speaker Change: Who are refractory to <unk> with.
Speaker Change: Have died due to acute graft versus host disease through four years and beyond.
Speaker Change: We're collaborating with the blood and bone marrow transplant clinical trials network and.
Speaker Change: One would have expected a much higher number to have died from acute gvhd is treated by other therapies.
Speaker Change: NIH funded body responsible for approximately 80% of all U S transplants to conduct this pivotal trial and Youll hear more about that in due course next.
Speaker Change: Next slide please.
Speaker Change: Next slide please.
Speaker Change: What is the value of Brian so in treating pediatric patients with acute gvhd.
Rich: Let's move forward to the second platform technology, Rich, let me stroke cell immuno selected stroke III.
Speaker Change: Total benefits of patient outcomes using right also range between $3 2 million to $4 $1 million.
Rich: Positive cells that have expanded and used a local delivery into areas of inflammatory tissues.
Speaker Change: And this is based on health economic models for lifetime, Ultra rare disease and high impact short term therapies, including quality of life years gained.
Rich: Slide 25.
Rich: We move to the use of rich, let me stroke, so for chronic inflammatory low back pain due to degenerative disc disease.
Speaker Change: And the benefits comprise.
Rich: This is a disease that affects more than 7 million patients across the U S. Similar number of patients across the EU five.
Speaker Change: Long term survival cost offsets and cost savings.
Speaker Change: Next slide please.
Rich: After failure of.
Speaker Change: So for treating pediatric patients with <unk>.
Rich: After failure of non steroidal agents and other conservative therapies, there are minimal treatment options and in fact.
Speaker Change: <unk> Gvhd the recommended dosage around so based on our FDA approved label.
Rich: 50% of opioid prescriptions are for this particular indications that we all know.
Speaker Change: Is 2 million cells.
Speaker Change: Her kilogram bodyweight.
Rich: Problems with opioid addiction, and the epidemic of opioid overuse see generic prescription across the U S.
Speaker Change: Given intravenously twice per week for four consecutive weeks.
Speaker Change: Wholesale acquisition cost O'brien, Sol is 194000 or intravenous infusion across all body weights.
Rich: We have established that there is durable improvement in.
Rich: In pain on a single injection of ourselves in prior studies and currently are enough.
Rich: <unk> phase III trial.
Speaker Change: Next slide please.
Rich: If you go to the next slide Slide 26. This is the patient journey and really the point of this slide is to demonstrate how how rapidly patients go through conservative.
Speaker Change: This is mandatory hub that has been established terms Miami's Oblast. This is set up to assist patients with insurance coverage financial assistance and access programs.
Rich: Approaches to go through opioids, and then really what's lift our interventional therapies with all of the related.
Speaker Change: Ensuring that no patient has left behind in receiving this potentially lifesaving therapy.
Rich: Adverse complications we aim to be establishing a best in care.
Speaker Change: Our comprehensive patient services hub.
Speaker Change: It provides access.
Rich: Class best in class approach to the treatment of inflammatory back pain as soon as conservative treatments have failed.
Speaker Change: And helps patients their families and institutions.
Speaker Change: Next slide please.
Rich: Slide 27 summarizes that.
Ron: Ron So is.
Rich: Outcomes in the first phase III trial, where.
Is being made available for pediatric gvhd in the United States.
Rich: As you can see here the comparison was the change in pain from baseline in Red.
Ron: In March.
Ron: We are we are.
Ron: Protein this unit.
Ron: Staged stage manner.
Rich: Our product.
Ron: <unk> transplant centers with highest volume and with established experience using the <unk> product.
Rich: Rex let me stroke, so in combination with the carrier.
Rich: In comparison at month, 12, which was primary endpoint of the study in terms of pain reduction against that.
Ron: Establishing and have established already a targeted sales force with experience in bone marrow transplant centers.
Placebo control in Green.
Ron: 15 of the highest volume centers account for 50% of patients.
That difference is highly significant and just to put this into context.
Ron: And the 45 highest volume centers account for 80% of patients.
Rich: Minimal pain reduction that is seen in the green at 12 months is roughly what you would expect to see with opioid usage.
Marcellus Sentara: More about this from Marcellus Sentara in the Q&A session.
Rich: The difference between the two is a very large difference in terms of mean pain reduction, but I think it's important to note that this main pain reduction for the group as a whole and that 50% of patients treated with <unk> showed complete remission or no pain at all at 12 months.
Speaker Change: Beyond acute gvhd, we have a strategy to expand the label and established lifecycle for the products.
Speaker Change: 'twenty one please.
Speaker Change: In particular, we're focusing on inflammatory bowel disease inflammatory crohn's and ulcerative colitis.
Speaker Change: But solidly in the clinical aspects of these diseases are very similar to the inflammatory bowel complications of acute graft versus host disease.
Rich: And those patients who were improved with pain at 12 months.
Rich: Three durable long term.
Rich: Maintenance of pain free outcomes through 36 months.
Speaker Change: And.
Speaker Change: The ability to respond to or I answer is similar and has been a value added in previous studies.
Rich: Moreover, 40% of patients who are on opioids.
Rich: At commencement of the study.
Rich: And despite the fact that they withheld and their physicians were told not to change medications.
Speaker Change: The unmet need is large in.
Speaker Change: In both adults and children.
Speaker Change: And in particular more than 60% of patients fail to respond or subsequently lose response to anti TNF agents, which are the first line.
<unk>.
Rich: Almost 30% of patients.
Rich: In the treated arms were able to completely come off opioids.
Speaker Change: Biologics in this patient population.
Rich: Versus.
Rich: Mid single digits in the control arm and this was a significant outcome.
Speaker Change: 25% of all inflammatory bowel disease patients.
Rich: So.
Rich: Currently were enrolling this trial.
Speaker Change: <unk> age and in these patients and anti TNF agent is the only approved therapy.
Rich: We're increasing the enrollment rates through various.
Speaker Change: This represents potentially as many as 7000 children.
Rich: Interventions, including increasing sites from 15 to 40 sites and we'll be updating the market shortly in due course.
Speaker Change: 50% to 60% of whom are.
Speaker Change: Likely to be refractory to anti TNF therapies, and we're essentially right on so may have.
Rich: Next slide please.
Speaker Change: Slide 29.
Speaker Change: May make a difference.
Speaker Change: Let's move to rich, let me stroke, so for ischemic heart failure.
Next slide please.
Speaker Change: Recent pilot study in adults demonstrating positive outcomes with ROI on so.
Speaker Change: Heart failure with low ejection fraction due to underlying ischemia continues to be a major problem in the western world and the U S more broadly increasing in prevalence and associated with a high risk of death heart attacks strokes.
Speaker Change: Directly injected submucosal layer in biologic refractory patients.
Speaker Change: <unk> was.
Speaker Change: Delivered a direct in the coffee injections to areas of inflammation.
Speaker Change: In addition, we have data showing that Remy stem cell and juices early remission in Crohn's disease adults, who failed a single anti TNF agents following of course, an intravenous treatment.
Speaker Change: Yes.
Speaker Change: Heart failure with low ejection fraction.
Speaker Change: Occurs in about 50% of all patients with heart failure with 60% of these patients have hot-blooded Judah ischemia.
Speaker Change: Given the effectiveness of round, so we're treating children with.
Speaker Change: Guestroom.
Speaker Change: They are at highest risk of cardiac events, including death.
Speaker Change: Testimony related gvhd with inflammation of the gut and the existing data in adult chronic disease patients.
Speaker Change: <unk> market is very large in the U S likely to be around 1 million patients with ischemic heart failure and inflammation.
Speaker Change: We plan to further evaluate the immuno module three effects of round so on Gi inflammation in medically refractory pediatric crohn's disease, and ulcerative colitis patients.
Speaker Change: Slide 30 please.
This is a complex slide we have shown this previously where the patient journey for.
Speaker Change: Next slide please.
Speaker Change: In addition to inflammatory bowel disease, we have.
Speaker Change: Heart failure is on the left hand side.
Speaker Change: Our strategy to expand <unk> use in adult patients with gvhd.
Speaker Change: New York Heart Association class, one and class to the bulk of heart failure patients.
Speaker Change: These patients are on a whole range of different oral medications, but inexorably over five years to 10 years of the disease. They move into the class III class for end stage spec.
Speaker Change: This continues to be an unmet needs, particularly in patients who fail <unk>. The only approved drug in adults with gvhd. This accounts for about.
Speaker Change: <unk>, 40% to 45% of all Russell isn't it treated patients. In addition survival of these patients with <unk> is very dismal.
Speaker Change: Spectrum, despite being on maximal oral therapy, they move into this area of high risk for progression to death.
Speaker Change: Around 20%, 30% by 100 days.
Speaker Change: We have performed two large randomized controlled studies in this patient population.
Speaker Change: For this patient population there are no approved therapies.
Speaker Change: <unk> in a pilot study of third line agents.
Speaker Change: Dream trial 537 patients in class III and the <unk>.
Speaker Change: Using Rai also demonstrated 73% survival at day 100.
Speaker Change: <unk> MPC trial of 159 patients both randomized controlled studies that is an end stage patients being kept alive by an artificial device.
Speaker Change: That provides us with the confidence to move forward into an appropriate.
Speaker Change: Pivotal study in adults.
Speaker Change: Next slide please slide 31.
O'brien: O'brien unsold.
Speaker Change: This slide shows the effect on cardiovascular deaths.
Speaker Change: Who are refractory to Russell isn't it with.
Speaker Change: We're collaborating with the blood and bone marrow transplant clinical trials network.
Speaker Change: All of our single MPC injection.
Speaker Change: NIH funded body responsible for approximately 80% of all U S transplant to conduct this pivotal trial and you'll hear more about that in due course. Thanks.
Speaker Change: In our phase III trial on the left hand side in patients who are.
Speaker Change: Categorized on the basis pre specified of a simple blood test for inflammation called CRP.
Speaker Change: Next slide please.
Speaker Change: Let's move forward to the second platform technology, Rich, let me stroke cell immuno selected stroke <unk> III.
Speaker Change: And on the right hand side.
Speaker Change: Slightly more fancy measurement of inflammation measuring cytokine called interleukin six.
Speaker Change: Positive cells that have expanded and used a local delivery into areas of inflammatory tissues.
Speaker Change: <unk> seen both the lift and the right panels is a control patients have a very high risk of cardiovascular death over a five year follow up period.
Speaker Change: Slide 25.
Speaker Change: We move to the use of rich, let me stroke, so for chronic inflammatory low back pain due to degenerative disc disease.
Speaker Change: And in both analyses a single interim cardiac injection of $150 million.
Speaker Change: This is a disease that affects more than 7 million patients across the U S. Similar number of patients across the EU five.
Speaker Change: Mtbc's or.
Speaker Change: <unk>, let me stress cells significantly reduced the risk of cardiovascular death by approximately.
Speaker Change: After failure of.
Speaker Change: After failure of nonsteroidal agents and other conservative therapies, there are minimal treatment options and in fact.
Speaker Change: 80% in the CRP.
Speaker Change: Categorization on the left and by about 60%.
Speaker Change: 50% of opioid prescriptions are for this particular indications that we all know.
Speaker Change: <unk> patients.
Speaker Change: By higher LOE IL six levels.
Speaker Change: Problems with opioid addiction, and the epidemic of opioid overuse subscription across the U S.
Speaker Change: Hi.
Speaker Change: <unk>.
Speaker Change: Demonstrates is that despite the fact patients.
Speaker Change: We have established that there's durable improvement in.
Speaker Change: Apparently well treated with a range of approved drugs for heart failure, which improves the symptoms and reduces their hospitalizations due to symptomatic shortens of breath I remain, particularly if they've got measurable inflammation. They remain at high risk for death.
Speaker Change: In pain from a single injection of our cells in prior studies and currently arena.
Speaker Change: <unk> phase III trial.
If you go to the next slide Slide 26. This is a patient journey and really the point of this slide is to demonstrate how how rapidly patients go through conservative.
Speaker Change: Which over the subsequent 345 years of follow up and that a single injection of <unk>, Let me stroke, so substantially rich <unk> that long term risk of death.
Speaker Change: Approaches the go through opioids, and then really what's lift our interventional therapies with all of the related at all.
Speaker Change: Next slide 32.
Speaker Change: This complications we aim to be establishing a best in care.
Speaker Change: Also from the.
Speaker Change: Recently published paper in the European Journal of Heart failure.
Speaker Change: Class best in class approach to the treatment of inflammatory back pain as soon as conservative treatments have failed.
Speaker Change: We analyzed.
Positive endpoints, which were pre specified from the dream trial.
Speaker Change: The two point based on the lift or $3 <unk> on the right.
Speaker Change: Slide 27 summarizes that.
Speaker Change: The.
Speaker Change: This being defined as.
Speaker Change: Outcomes in the first phase III trial.
Speaker Change: Time to either cardiovascular death or heart attack or stroke.
Speaker Change: Yeah.
Speaker Change: As you can see here the comparison was the change in pain from baseline in Red.
Speaker Change: <unk> is just time to heart attack stroke, and what Youre seeing both analyses is that overall.
Speaker Change: All about product.
Rick: Rick let me stroke, so in combination with the carrier and.
Speaker Change: Patients shared.
Rick: In comparison at month, 12, which was primary endpoint of the study.
Speaker Change: A significant reduction in heart attacks or stroke.
Speaker Change: There was no notable particularly in the setting of ischemia.
Rick: A pain reduction against.
Speaker Change: And in the setting of inflammation and most notably.
Rick: Placebo controlling green.
Rick: That difference is highly significant and just to put this into context.
Speaker Change: The greatest risk reduction, 90% risk reduction of heart attack stroke.
Rick: Minimal pain reduction that is seen in the green at 12 months is roughly what you would expect to see with opioid usage.
Speaker Change: And.
Speaker Change: Almost 50% risk reduction in heart attack stroke or death in those patients who had both ischemia and inflammation and that represents clearly the highest risk population and the population most likely to respond to a single treatment of ourselves.
Rick: The difference between the two is a very large difference in terms of mean pain reduction, but I think it's important to note that this is main pain reduction for the group as a whole and that 50% of patients treated with <unk> showed complete remission or no pain at all at 12 months.
We can go to slide 33 please.
Speaker Change: Based on.
Speaker Change: Meetings with the FDA, we have a clear pathway towards accelerated approval for <unk> in adults with heart failure with low ejection fraction.
Rick: And these patients who were improved with paying a 12 months very durable long term.
Speaker Change: Okay.
Speaker Change: Highlighted the outcomes from the Dream trial over a minimum median follow up of 30 months and beyond.
Rick: Maintenance of pain free outcomes through 36 months.
Rick: Moreover, 40% of patients who are on opioids.
Speaker Change: We also have results from the second <unk> study MPC number two which demonstrated that at 12 months of follow up there was a significant increase in the proportion of <unk> patients with ischemic failure heart failure to successfully win and then had a reduction in both hospitalizations and mortality.
Rick: At commencement of the study.
Rick: Despite the fact that though with hopes and their physicians would not have changed medications.
Rick: <unk>.
Rick: Almost 30% of patients.
Rick: In the treated arms were able to completely come off opioids.
Speaker Change: Based on the data from both of these trials when we met with the FDA. We were informed the totality of the trial results from these studies may support an accelerated approval pathway in this.
Rick: Versus.
Rick: Mid single digits in the control arm and this was a significant outcome.
Rick: So.
Speaker Change: <unk> heart failure patients with low ejection fraction on that basis, we intend to make with the FDA further.
Rick: Currently were enrolling this trial.
Rick: Increasingly enrollment rates through various.
Speaker Change: Our vacation on out various components of it one needs to go into a BLA filing.
Rick: Interventions, including increasing sites from 15 to 40 sites and we'll be updating the market shortly into course.
Speaker Change: To discuss clinical data, particularly the data that would be required for a confirmatory study in order to file for accelerated approval in as.
Speaker Change: Next slide please.
Speaker Change: Schemey patients with heart failure.
Speaker Change: Slide 29.
Speaker Change: Let's move to rich, let me stroke, so for ischemic heart failure.
Speaker Change: Slide 34.
Speaker Change: So I want to talk a lot more detail on additional areas of focus in cardiovascular disease, but.
Speaker Change: Heart failure with low ejection fraction due to underlying ischemia continues to be a major problem in the western world in the U S more broadly increasing in prevalence and associated with a high risk of death heart attacks and strokes.
Speaker Change: As I've previously highly.
Speaker Change: Highlighted we have also panel data in children with with congenital heart disease and.
Speaker Change: The HOKA plastic lift <unk> syndrome, where we have both on Amit orphan drug designation and rare pediatric disease designation based on the data that's been.
Speaker Change: It is.
Speaker Change: Heart failure with low ejection fraction.
Speaker Change: Occurs in about 50% of all patients with heart failure with 60% of these patients have hotbed of Judah ischemia.
Speaker Change: Accrued to date and we will be.
Speaker Change: Having meetings with the FDA.
Speaker Change: To discuss whether the controlled study can be used to support regulatory approval for this locked threatening condition using <unk>.
Speaker Change: That they are at highest risk of cardiac events, including death.
Speaker Change: <unk> market is very large in the U S likely to be around 1 million patients with ischemic heart failure and inflammation.
Speaker Change: And my final slide if we can go now to slide 36 is where we see.
Speaker Change: Slide 30 please.
Speaker Change: Key objectives for each of our programs over the coming six to 12 months and really we have three major.
Speaker Change: This is a complex slide we have shown this previously where the patient journey for heart failure is on the left hand side.
Speaker Change: Programs and products and objectives for I answer, which is developed for pediatric and adult inflammatory diseases.
Speaker Change: New York Heart Association class, one and cost to the bulk of heart failure patients.
Speaker Change: And so we will be available for use in steroid refractory acute gvhd at U S hospitals this quarter.
Speaker Change: These patients are on a whole range of different oral medications, but inexorably over five years to 10 years of the disease. They move into the class III class four and end stage spectrum, despite being on maximal oral therapy. They move into this area of high risk for progression.
Speaker Change: Studies will commence in both pediatric and adult label extension indications as I've talked about including adult Gvhd and <unk>.
Patrick: Patrick and adult inflammatory bowel disease <unk>.
Patrick: <unk> for heart failure in adults with low ejection fraction heart failure and in children congenital heart disease.
Speaker Change: To death.
Speaker Change: We have performed two large randomized controlled studies in this patient population the.
Patrick: And being <unk>.
Speaker Change: The Dream trial 537 patients in class III and the <unk> MPC trial at 159 patients. Both randomized controlled studies that is an end stage patients being kept alive by an artificial device.
Patrick: <unk> for meetings with the agency for accelerated approval filing.
Rex: Finally, Rex let me stroke, so for chronic low back pain.
Rex: We have a phase III trial that is that we have and will continue to actively progress and invest in order to accelerate enrollment across multiple sites across the U S.
Speaker Change: Next slide please slide 31.
Speaker Change: This slide shows the effect on cardiovascular deaths.
Rex: This is a 12 month primary endpoint of pain reduction.
Speaker Change: All of a single MPC injection.
Rex: Subsequent to which we could be in a position to file for approval.
Speaker Change: In our phase III trial on the left hand side in patients who are.
Rex: And then the other thing I'll stop and thank you very much like to open it up to two questions. Please.
Speaker Change: <unk> categorized on the basis pre specified Sims.
Speaker Change: Simple blood test for inflammation called CRP.
Rex: Thank you.
Speaker Change: And on the right hand side.
Rex: If you wish to ask a question. Please press star one on your telephone and wait for your name to be announced.
Speaker Change: Slightly more fancy measurement of inflammation measuring cytokine called interleukin six.
Rex: If you wish to cancel your request please press star two.
Speaker Change: <unk> seen both the lift and the right panels is the control patients have a very high risk of cardiovascular death over a five year follow up period.
Rex: If you're on speakerphone, please pick up the handset to ask a question.
Edward <unk>: We have the first question from the line of Edward <unk> from Piper Sandler. Please go ahead.
Speaker Change: And in both analyses a single interim cardiac injection.
Rex: Okay.
Rex: Okay.
$150 million.
Rex: A lot of really exciting things going on here I'm wondering if you could just with respect to the <unk> launch and I appreciate the color on the.
Speaker Change: Mpc's.
Speaker Change: Rex, let me stroke sells significantly reduced the risk of cardiovascular death.
Speaker Change: By approximately.
Rex: Pricing.
Speaker Change: 80% in the CRP.
Rex: How large is the sales force and because you sort of have the expanded.
Speaker Change: Categorization on the left and by about 60%.
Rex: Program in place how many centers are already bringing on using <unk> Paul.
Speaker Change: <unk> patients.
Speaker Change: By higher LOE IL six levels.
Speaker Change: Hi.
Rex: So just trying to get a sense of how quickly this could really be launched in the U S. And then I have.
Speaker Change: <unk>.
Speaker Change: Demonstrates is that despite the fact patients.
Speaker Change: Apparently well treated with a range of approved drugs for heart failure, which improves the symptoms and reduces their hospitalizations due to symptomatic shortens of breath I remain particularly in the <unk>.
Rex: A quick follow up question. Thank you.
Rex: I'll just say that.
Rex: While <unk> is already standard of care in children with steroid refractory acute gvhd, we have been providing.
Speaker Change: I've got measurable inflammation, they remain at high risk for death.
Rex: Mentioned and at <unk>.
Speaker Change: Which over the subsequent 345 years of follow up and that a single injection of <unk>, Let me stress so substantially rich reduces that long term risk of death.
Rex: A number of.
Rex: Most physicians and most transplant centers are very familiar with the product and are waiting.
Literally waiting for this product.
Speaker Change: Next slide 32.
Rex: Commercially available so they can use it freely.
Speaker Change: Also from the.
Speaker Change: Recently published paper in the European Journal of Heart failure.
Rex: Yeah.
I'll ask Marcel Sentara could talk a little bit about his commercial team, which is already in place.
Speaker Change: We analyzed.
Speaker Change: Positive endpoints, which were pre specified from the dream trial.
Speaker Change: The two point based on the lift or $3 <unk> on the right.
Rex: As I mentioned earlier.
Rex: 80%.
Speaker Change: This being defined as.
Rex: Of the transplants performed across 45 sites.
Speaker Change: Time to either cardiovascular death or heart attack or stroke.
Rex: Marcello maybe you can talk about your.
Speaker Change: Pardon me. This is just time to heart attack stroke, and what you've seen both analyses is that overall.
Marcello: Strategies to get it across all of our sites.
Marcello: No that's great. So thank you very much everyone. Thank you for the question. It's a good one.
Speaker Change: Patient chart.
Marcello: So I think as Thiago mentioned right. So we have deals in our continued through through deals.
Speaker Change: Significant reduction in heart attacks or stroke.
Speaker Change: That was notable particularly in the setting of ischemia, particularly in the setting of inflammation and most notably.
Marcello: Our World Class sales force with transparent experience.
Marcello: It's a small appropriately size sales force.
Speaker Change: The greatest risk reduction, 90% risk reduction of heart attack stroke and.
Marcello: Nine in total.
Marcello: Our key account managers, along with the head of sales force.
Speaker Change: Almost 50% risk reduction in heart attack stroke or death in those patients who had both ischemia and inflammation and that represents clearly the highest risk population and the population most likely to respond to a single treatment of ourselves.
Marcello: That will be focusing on this 45 key transplant centers.
Marcello: Brazil will treat each transplant center and is a key target a key.
Marcello: Customer for us that represents 80% of the potential.
Marcello: Onboard and has already started actually started before we even higher.
Speaker Change: We can go to slide 33 please.
Speaker Change: So based on.
Marcello: The sales force we've been in discussions with.
In meetings with the FDA, we have a clear pathway towards accelerated approval for <unk> in adults with heart failure with low ejection fraction.
Marcello: A lot of the Santos at the moment, so, thereby thunder products available at the end of the month, we're ready to roll.
Speaker Change: <unk>.
Marcello: Yes, I would say the other point that's important is we've already had inquiries inbound inquiries from at least five to 10 for at least five to 10 children.
Speaker Change: Highlighted the outcomes from the Dream trial of a minimum median follow up of 30 months and beyond.
Speaker Change: We also have results from the second <unk> study MPC number two which demonstrated that at 12 months of follow up there was a significant increase in the proportion of <unk> patients with ischemic failure heart failure to successfully win and then had a reduction both hospitalizations and mortality base.
Marcello: Very sick, who were waiting for product as we scale.
Marcello: Well, that's great well it just shows you how important of a product.
Marcello: Really as the lifesaving product.
Marcello: My second question had to do with respect to the chronic lower back pain.
Speaker Change: Based on the data from both of these trials when we met with the FDA.
Marcello: The ongoing trial and again, that's being another really important product how far are you guys along in terms of.
Speaker Change: We're informed the totality of the trial results from these studies may support an accelerated approval pathway.
Speaker Change: Ischemic heart failure patients with low ejection fraction on that basis, we intend to make with the FDA further clarification on out various components of it one needs to go into a BLA filing.
Marcello: And when do you anticipate actually reporting data from that phase three trial as you recall from launching yourself you answered to seek a partner.
Marcello: Well I would say that if we're successful this is a huge market opportunity I mentioned earlier, there's about 7 million people in the U S same type of number in EU five to meet the criteria.
Speaker Change: To discuss clinical data, particularly the data that would be required for a confirmatory study in order to file for accelerated approval.
Speaker Change: Ischemic patients with heart failure.
Marcello: Patients are being enrolled at this for this trial.
Speaker Change: Slide 34.
Marcello: And.
Speaker Change: So I want to talk a lot more detail on additional areas of focus in cardiovascular disease, but.
Marcello: If successful our single injectable it will be a major immuno module three.
Speaker Change: As I previously.
Marcello: Pain management therapeutic.
Speaker Change: Highlighted we have also panel data in children with with congenital heart disease and.
Marcello: You can imagine that.
Marcello: Sales force required.
Marcello: Targeting of this patient population is substantial.
Speaker Change: The HOKA plastic lift <unk> syndrome, where we have both on Amit orphan drug designation and rare pediatric disease designation based on the data that's been.
Marcello: In Europe, we already have.
Marcello: Commercial partnering Grunenthal largest.
Marcello: Number one.
Marcello: Company in the pain space they have the expertise across the major jurisdictions in both in terms of the regulatory and reimbursement.
Speaker Change: Accrued to date and we will be.
Speaker Change: Having meetings with the FDA.
Speaker Change: To discuss whether the controlled study can be used to support regulatory approval for this locked threatening condition using <unk>.
Marcello: Would presumably enter into a similar partnership in the U S.
Marcello: Rather than invest our own.
Speaker Change: And my final slide if we can go now to slide 36 is where we see.
Marcello: Distribution.
Marcello: Okay.
Marcello: Youre going to see a ramp up.
Speaker Change: Key objectives for each of our programs over the coming six to 12 months and really we have three major.
Marcello: Of of.
Enrollment.
Marcello: In short order.
Speaker Change: Programs and products and objectives for I answer, which is developed for pediatric and adult inflammatory diseases.
Marcello: <unk> invested substantially.
Marcello: In sides.
Marcello: The number of centers that are coming on board that are on board now.
Speaker Change: And so we will be available for use in steroid refractory acute gvhd at U S hospitals this quarter.
Marcello: <unk> <unk>, we expect over the coming four weeks to get up to about 40.
Speaker Change: Studies will commence.
Speaker Change: Pediatric and adult label extension indications as I've talked about including adult Gvhd and <unk>.
Marcello: And what happens is that as the physicians have more and more experience in terms of screening.
Marcello: Evaluating churning through the <unk>.
Speaker Change: <unk> and adult inflammatory bowel disease <unk>.
Marcello: Backlog of patients it becomes easier and you get that sort of hockey stick takeoff.
Speaker Change: <unk> for heart failure in adults with low ejection fraction heart failure any children with congenital heart disease.
Marcello: And so we have something like <unk>.
Speaker Change: I'm being.
Marcello: 20 patients currently in screening.
Speaker Change: <unk> for meetings with the agency for accelerated approval filing.
On a weekly basis that turns into.
Speaker Change: Finally, richland stroke, so for chronic low back pain.
Marcello: An additional 15 to 20 new patients.
Speaker Change: We have a phase III trial that is that we have and will continue to actively progress and invest in order to accelerate enrollment across multiple sites across the U S.
Marcello: These numbers are rapidly increasing so we have a target enrollment but towards the end of this year, but if we can compress it and bring it.
Marcello: Foster inland, we'll certainly try to do so.
Speaker Change: This is a 12 month primary endpoint of pain reduction.
Marcello: That's really helpful. I know a lot of a lot of my friends, who are interested in a product like that so keep up the good morning. Thanks for answering the question.
Speaker Change: Subsequent to which we could be in a position to file for approval.
Speaker Change: That's not a thing I'll stop and thank you very much like to open it up to two questions. Please.
Marcello: Thank you.
Marcello: Okay.
Marcello: Thank you.
Michael: We have the next question from the line of Michael <unk> from Maxim Group. Please go ahead.
Speaker Change: Thank you.
Speaker Change: If you wish to ask a question. Please press star one on your telephone and wait for your name to be announced.
Michael: Hey, guys. Thank you so much for taking my questions today and congratulations on all the exciting progress.
Speaker Change: If you wish to cancel your request please press star two.
Michael: Thank you.
Speaker Change: If you're on speakerphone, please pick up the handset to ask a question.
Michael: I guess just to kick things off quickly looking at the math.
Michael: The WAC price of 194000 per injection eight injections.
Speaker Change: We have the first question from the line of Edward <unk> from Piper Sandler. Please go ahead.
Michael: One in about one $5 million per course of treatment on getting that right and then just what sort of feedback have you gotten from payers on this pricing level.
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: A lot of really exciting things going on.
Speaker Change: I'm wondering if you could just with respect to the <unk> launch and I appreciate the color on the.
Michael: Okay.
Michael: Well again, let me, let me start by saying that based on health economic models, which reflect net positive benefits of treatment with <unk> of between three two to $4 1 million, we have set the price per infusion.
Speaker Change: Pricing.
Speaker Change: Large is the sales force and because you sort of had the extended.
Speaker Change: Program in place how many centers are already screening on using <unk> Paul.
Michael: $194000.
Michael: Recommended dose for a child.
Speaker Change: So just trying to get a sense of how quickly this could really be launched in the U S. And then I have a quick follow up question. Thank you.
Michael: With steroid refractory Gvhd twice weekly infusions of 2 million cells per kilogram for four weeks.
Michael: So really the price that we've set per infusion is based on the economic value of the treatment.
Speaker Change: I'll just say that.
Speaker Change: While <unk> is already standard of care in children with steroid refractory acute gvhd, we have been providing.
Michael: Products available this quarter for physicians to order.
Michael: The question around.
Speaker Change: Mentioned hundreds and it actually brought a number of.
Michael: Physicians see the product areas and solid based on the efficacy.
Speaker Change: Most physicians and most transplant centers are very familiar with the product and are waiting.
Michael: And on the results delivered to date and on the long term survival benefits.
Speaker Change: Literally waiting for this product.
Michael: Given the high mortality rate of this disease and the absence of any other treatment oven right answer for children under 12.
Speaker Change: Commercially available so they can use it freely.
Speaker Change: Yeah.
Michael: I think everybody is pretty keen.
Andrew Shepherd: I'll ask Marcellus Sentara could talk a little bit of that his commercial team, which is already in place.
Michael: To get hold of the product.
Michael: Hello, you might want to.
Michael: China and Europe, Europe tandem you let the.
Speaker Change: As I mentioned earlier.
Michael: Our clinical commercial interactions with all the payers.
Andrew Shepherd: 80%.
Andrew Shepherd: The transplants performed across 45 sites.
Michael: The various applications and so that's addressable <unk> so first of all tandem.
Andrew Shepherd: Marcel or maybe you can talk about your.
Michael: We soft tandem is our scientific launch.
Andrew Shepherd: Strategies to get it across all of our sites.
Michael: We had most of our activities during the convention I think we could see the <unk>.
Speaker Change: At least that's great. So thank you very much here, but thank you for the question. It's a good one.
Michael: Enthusiasm for the products in the lab of questions asked in terms of availability.
Andrew Shepherd: So I think as Thiago mentioned we.
Speaker Change: <unk> deals and are continue to be a loss.
Michael: When people can extra start prescribing the product for us it was.
Speaker Change: Our World Class sales force with transparent experience.
Michael: Very very encouraging and the feedback that we received through more centers.
Speaker Change: It's a small appropriately size sales force.
Speaker Change: Nine in total.
Michael: Also very well are very important for US right. So tandem was a successful scientific launch now in terms of engagement with payers, obviously, we've been engaging with payers.
Speaker Change: Key account managers, along with the head of the sales force.
Speaker Change: That will be focusing on this 45 key transplant centers.
Speaker Change: Because you will treat each transplant center.
Michael: For quite some time now I think there is an appreciation for the lower number of kids that is affected by this condition.
Speaker Change: As a key target are key.
Speaker Change: Customer for us that represents 80% of the potential.
Michael: 375.
Speaker Change: Onboard and has already started actually started before we even higher.
Michael: And also like this with silver mentioned this price is fair when you consider the benefit.
Speaker Change: Salesforce, we've been in discussions with.
Speaker Change: A lot of the Santos at the moment, so, thereby the thunder products available at the end of the month, we're ready to roll.
Michael: Ryan also provides for these kids.
Speaker Change: So overall I think the discussions that would be very positive I think there was an appreciation for the burden of the disease and there is also an appreciation for the long term survival of our onshore offers these patients. So we are very optimistic.
Speaker Change: Yeah, and I would say the other point that's important is we've already had inquiries inbound inquiries.
Speaker Change: At least five to 10 or at least five to 10 children.
Michael: And we're looking forward to the next steps.
Very sick, who were waiting for product as we scale.
Speaker Change: Alright. Thank you for that additional color and then just one more from me I wanted to see if you had.
Speaker Change: Well, that's great well it just shows you how important of a product that's really is lifesaving products.
Speaker Change: Any thoughts regarding December FDA draft guidance on accelerated approval.
Speaker Change: My second question had to do with respect to the chronic lower back pain.
Speaker Change: Particularly how that could pertain to the class four heart failure program is there an expectation that youll need to start up the class Q3 confirmatory.
Speaker Change: Ongoing trial and again, that's being another really important product how far are you guys along in terms of enrollment and when.
Speaker Change: In that filing and then just what are your thoughts on timing and next steps to get that confirmatory study gallon.
Speaker Change: When do you anticipate actually reporting data from that Phase III trial is your goal for launch out yourselves you answered to seek a partner.
Speaker Change: Yes, I think I think this is the key the right key question, we expect to be meeting with the FDA.
Speaker Change: Well I would say that if we're successful this is a huge market opportunity I mentioned earlier that was about 7 million people in the U S same type of number in the EU five.
Speaker Change: Coming month, or so two months or so.
Speaker Change: Timeframe to clarify exactly exactly that.
Speaker Change: <unk>.
Speaker Change: The criteria.
Speaker Change: Put into it.
Speaker Change: Patients are being enrolled at this for this trial.
Speaker Change: The circled briefing book.
Speaker Change: We reviewed by FDA.
Speaker Change: And.
Speaker Change: If successful a single injectable it will be a major immuno module treat.
Speaker Change: Clinical trial design and the components of a confirmatory study that we would want to do post accelerated approval.
Speaker Change: Pain management therapeutic.
Speaker Change: And so the details of that are really what we wanted to discuss with the FDA we would expect.
Speaker Change: You can imagine that.
Speaker Change: Sales force required.
Speaker Change: Targeting this patient population is substantial.
Speaker Change: Given the severity of the patients with advanced <unk>.
Speaker Change: In Europe, we already have.
Speaker Change: Commercial partner Grunenthal largest.
Speaker Change: In the end stage heart failure, and the mortality benefit that we've shown that the FDA would want us to.
Speaker Change: Number one.
Speaker Change: Company in the pain space they have the expertise across the major jurisdictions in but I think the regulatory and reimbursement.
Speaker Change: Product.
Speaker Change: On marketing as soon as possible and.
Speaker Change: The arrangements or the discussions with the FDA around.
Speaker Change: Would presumably enter into a similar partnership in the U S.
Speaker Change: The start up.
Speaker Change: Rather than invest our own.
Speaker Change: The agreement on the on.
Speaker Change: From a confirmatory trial design itself I think.
Speaker Change: Distribution.
Speaker Change: What would be a gating events.
Speaker Change: Okay.
Speaker Change: You're going to see a ramp up.
Speaker Change: I'll come back to the street as soon as we.
Speaker Change: Of of.
Speaker Change: Have more clarity on that.
Speaker Change: Enrollment.
Speaker Change: In short order.
Speaker Change: Alright, Thank you very much once again for taking my questions today.
Speaker Change: Invested substantially in sides.
Speaker Change: Thank you.
Speaker Change: The number of centers.
Thank you.
Speaker Change: Coming onboard that are on board now.
Speaker Change: There are no further questions at this time.
Speaker Change: As approximately 15, we expect over the coming four weeks to get up to about 40.
Speaker Change: I'll now hand back to Dr. <unk> for closing comments.
Speaker Change: Right.
Speaker Change: And what happens is that as the physicians have more and more experience in terms of screening.
Speaker Change: Want to thank.
Speaker Change: Everybody on the line is listen to our presentation today, we couldnt be more excited.
Speaker Change: Evaluating churning through the.
Speaker Change: About how rapidly we are delivering this product to the children, who needed as a lot of work.
Speaker Change: Backlog of patients it becomes easier and you get that sort of hockey stick takeoff.
Speaker Change: That is going on behind the scenes at every level in the company from commercial to manufacturing to regulatory.
Speaker Change: So we have something like.
Speaker Change: 20 patients currently in screening.
Speaker Change: And that on a weekly basis that turns into.
Speaker Change: And.
Speaker Change: The amount of effort, that's going to doing this right and doing it in a way that that we will save lives and we're going to work with our partners the physician the institutions and the families to make sure that we deliver.
Speaker Change: An additional 15% to 20 new patients.
Speaker Change: These numbers are rapidly increasing so we have a target enrollment.
Speaker Change: Towards the end of this year, but if we can compress it and bring it.
Speaker Change: Pastor in then we'll certainly try to do so.
Speaker Change: Top quality product that is going to save a lot of lives.
Speaker Change: That's really helpful. I know a lot of a lot of my friends, who are interested in a product like that so keep up the good work. Thanks for answering the questions. Thank.
Speaker Change: Sure.
Speaker Change: Today was a summary of the activities in the last six months and I think youre going to hear a lot more from us.
Speaker Change: Thank you.
Speaker Change: In short order as we move forward to start.
Speaker Change: Thank you.
Speaker Change: We have the next question from the line of Mike <unk> from Maxim Group. Please go ahead.
Speaker Change: Putting up.
Speaker Change: Making it available in the marketplace.
Mike: Hey, guys. Thank you so much for taking my questions today and congratulations on all the exciting progress.
Speaker Change: The physicians and healthcare providers.
Speaker Change: Thank you.
Speaker Change: Thank you.
Speaker Change: I guess just to kick things off quickly looking at the math.
Speaker Change: The WAC price of 194000 per injection eight injections.
Speaker Change: One in about one $5 million per course of treatment I am I getting that right and then just what sort of feedback have you gotten from payers on this pricing level.
Speaker Change: Okay.
Speaker Change: Well again, let me, let me start by saying that based on health economic models, which reflect a net positive benefits of treatment with the right answer look between three two to $4 $1 million, we have set the price per infusion.
Speaker Change: $194000.
Speaker Change: Recommended dose for a child.
Speaker Change: With steroid refractory Gvhd twice weekly infusions of 2 million cells per kilogram or four weeks.
Speaker Change: So really the price that we've set per infusion is based on the economic value of the treatment.
Speaker Change: Products available this quarter for physicians to order.
Speaker Change: The question around.
Speaker Change: Physicians see the product theaters and totally based on the clinical efficacy.
Speaker Change: And on the results delivered to date and on the long term survival benefits.
Speaker Change: Given the high mortality rate of this disease and the absence of any other treatment oven right answer for children under 12, So I think everybody's pretty keen to.
Speaker Change: To get hold of the product.
Speaker Change: Hello, you might want to.
Speaker Change: China and Europe.
Speaker Change: Tandem you, let the clinical commercial interactions with all the payers.
Speaker Change: Various definitions so that drives both <unk> so first of all tandem.
Speaker Change: Soft tandem is our scientific launch.
Speaker Change: Most of our activities during the convention I think we could see the the <unk>.
Speaker Change: Enthusiasm for the products and the level of questions asked in terms of availability.
Speaker Change: When people can extra start prescribing the product for us it was.
Speaker Change: Very very encouraging and the feedback that we received through most centers.
Speaker Change: Also very well are very important for US right. So tandem was a successful scientific launch now in terms of engagement with payers, obviously, we've been engaging with all base.
Speaker Change: For quite some time now I think there is an appreciation for the low number of kids that is affected by this condition.
Speaker Change: 375.
Speaker Change: And also like this silver mentioned this price is fair when you consider the benefit.
Speaker Change: <unk> also provides to these kids. So overall I think the discussions that would be very positive I think there was an appreciation for the burden of the disease and there is also an appreciation for the long term survival and also offer these patients. So we are very optimistic.
Speaker Change: And we're looking forward to the next steps.
Speaker Change: Alright. Thank you for that additional color and then just one more from me I wanted to see if you had.
Speaker Change: Any thoughts regarding December FDA draft guidance on accelerated approval.
Speaker Change: Particular, how that could pertain to the class four heart failure program is there an expectation that youll need to start up the class two three confirmatory and in that filing and then just what are your thoughts on timing and next steps to get that confirmatory study gallon.
Speaker Change: Yeah, I think I think this is the key the right key question.
Speaker Change: To be meeting with the FDA.
Coming month, or so two months or so.
Speaker Change: Timeframe to clarify exactly exactly that.
Speaker Change: <unk>.
Speaker Change: Put into it.
Speaker Change: The so called briefing book with that.
Speaker Change: We reviewed by FDA.
Speaker Change: Clinical trial design and the components of a confirmatory study that we would want to do post accelerated approval.
Speaker Change: And so the details of that are really what we wanted to discuss with the FDA we would expect.
Speaker Change: Given the severity of the patients with advanced <unk>.
Speaker Change: End stage heart failure, and the mortality benefit that we've shown that the FDA would want us to.
Speaker Change: Product on market as soon as possible and.
Speaker Change: The arrangements or the discussions with the FDA around.
Speaker Change: The start up.
Speaker Change: The agreement on it.
Speaker Change: On the confirmatory trial design itself I think.
Speaker Change: Would be a gating events.
I'll come back to the street as soon as we have more clarity on that.
Speaker Change: Alright, Thank you very much once again for taking my questions today.
Speaker Change: Thank you.
Speaker Change: There are no further questions at this time.
Speaker Change: I'll now hand back to Dr. <unk> for closing comments.
Speaker Change: Great.
Speaker Change: I want to thank.
Speaker Change: Everybody on the line is listen to our presentation today, we couldnt be more excited about <unk>.
Speaker Change: Happily with delivering this product to the children, who needed as a lot of work.
Speaker Change: That is going on behind the scenes at every level in the company from commercial to manufacturing to regulatory.
Speaker Change: And.
Speaker Change: The amount of effort, that's going to doing this right and doing it in a way that that we will save lives and we're going to work with our partners the physician institutions and the families to make sure that we deliver.
Speaker Change: Top quality product that is going to save a lot of lives.
Speaker Change: <unk>.
Speaker Change: Today was a summary of the activities in the last six months and I think youre going to hear a lot more from us.
Speaker Change: In short order as we move forward to start.
Speaker Change: Putting out.
Speaker Change: Making it available in the marketplace.
Speaker Change: Physicians and healthcare providers.
Speaker Change: Thank you.
Speaker Change: Thank you.
That does conclude our conference for today. Thank you for participating you may now disconnect.
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: [music].