POSITIVE OUTCOMES OF FIRST CHILDREN TREATED WITH REMESTEMCEL-L FOR MULTISYSTEM INFLAMMATORY SYNDROME (MIS-C) AND HEART FAILURE POSTCOVID-19 PUBLISHED IN PEDIATRICS

Melbourne, Australia; February 17, and New York, USA; February 16, 2021: Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, today announced that Pediatrics (Journal of the American Academy of Pediatrics) has published a paper on the first two children treated with Mesoblast’s mesenchymal stromal cell (MSC) product candidate remestemcel-L for life-threatening multisystem inflammatory syndrome (MIS-C) associated with COVID-19.

The manuscript, titled ‘Remestemcel-L Therapy for COVID-19-Associated Multisystem Inflammatory Syndrome in Children,’ was based on two children admitted to the Medical University of South Carolina’s MUSC Shawn Jenkins Children’s Hospital, who were the first ever to be treated with remestemcel-L for MIS-C. Its authors include Allison Ross Eckard, MD, Professor of Pediatrics and Medicine and Division Chief of Infectious Diseases and Dr. Andrew M. Atz, Professor and Chair of the Department of Pediatrics at the Medical University of South Carolina. The article can be accessed at https://doi.org/10.1542/peds.2020-046573

MIS-C, a potentially life-threatening inflammatory condition which involves multiple critical organs and their vasculature, is associated with prior rather than active COVID-19 infection. It is thought to be a post-viral autoimmune process where the body’s over-zealous reaction to the virus causes the damage, rather than the virus itself. In approximately 50% of cases this inflammation is associated with significant cardiovascular complications resulting in decreased heart function and the presence of clinically important cardiovascular symptoms.1-3

MESOBLAST PHASE 3 TRIAL SHOWS THAT A SINGLE INJECTION OF REXLEMESTROCEL-L + HYALURONIC ACID CARRIER RESULTS IN AT LEAST TWO YEARS OF PAIN REDUCTION WITH OPIOID SPARING ACTIVITY IN PATIENTS WITH CHRONIC LOW BACK PAIN DUE TO DEGENERATIVE DISC DISEASE

Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, today announced results from the Phase 3 randomized controlled trial of its allogeneic mesenchymal precursor cell (MPC) therapy rexlemestrocel-L in 404 enrolled patients with chronic low back pain (CLBP) due to degenerative disc disease (DDD) refractory to conventional treatments. The results indicate that a single injection of rexlemestrocel-L may provide a safe, durable, and effective opioidsparing therapy for patients with chronic inflammatory back pain due to degenerative disc disease, and that greatest benefits are seen when administered earlier in the disease process before irreversible fibrosis of the intervertebral disc has occurred.

“The durable pain reduction for at least two years from a single administration indicates that rexlemestrocel-L has the potential to change the treatment paradigm for chronic low back pain due to inflammatory disc disease, a condition that affects as many as seven million patients across the United States and Europe, and to prevent or reduce opioid use and dependence” said Dr Silviu Itescu, Chief Executive Officer of Mesoblast.

DISC: Previously held

I would ask existing and prospective shareholders to go back and read the annual reports for the past 15 years.

Management uses the same playbook over and over:

- Find blue sky opportunity

- Promise it's close

- Fail

- Repeat

Everytime they raise money, they invite institutional shareholders to Rockpool (a nice Neil Perry restaurant) in Sydney to eat a lavish lunch, using money raised from shareholders.

Mesoblast's superpower is to find different pools of capital to tap, for the past decade. It has yet to learn how to make money for shareholders.

Management drink cocktails made from the tears of past shareholders.

It is impressive they continue to find new pools of money to burn. 

MESOBLAST UPDATE ON COVID-19 ARDS TRIAL

Disc: I have held in the past

MSB are looking at opening at $3.00 after pre closing price ( before trading halt ) of $3.77

MESOBLAST PROVIDES TOPLINE RESULTS FROM PHASE 3 TRIAL OF REXLEMESTROCEL-L FOR ADVANCED CHRONIC HEART FAILURE

Melbourne, Australia; December 15, and New York, USA; December 14, 2020: Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, today announced top-line results from the landmark DREAM-HF Phase 3 randomized controlled trial of its allogeneic cell therapy rexlemestrocel-L (REVASCOR®) in 537 patients with advanced chronic heart failure1.

Over a mean 30 months of follow-up, patients with advanced chronic heart failure who received a single endomyocardial treatment with rexlemestrocel-L on top of maximal therapies had 60% reduction in incidence of heart attacks or strokes and 60% reduction in death from cardiac causes when treated at an earlier stage in the progressive disease process. Despite significant reduction in the pre-specified endpoint of cardiac death, there was no reduction in recurrent non-fatal decompensated heart failure events, which was the trial’s primary endpoint. This suggests that rexlemestrocel-L reduces mortality by mechanisms that are distinct from those of existing drugs that reduce hospitalization rates but do not significantly impact cardiac mortality.

“There is an urgent need for new therapies that can reduce the high death rates in heart failure patients by different modes of action from existing drugs which reduce hospitalization rates but have not significantly reduced mortality rates,” said Mesoblast Chief Executive Dr Silviu Itescu. “The reduction in mortality seen with rexlemestrocel-L in advanced chronic heart failure underlines the power of this technology and the commitment of Mesoblast to address diseases in patients with high unmet need which are refractory to existing therapies.”

Key highlights were that a single injection of rexlemestrocel-L, on top of maximal therapy, resulted in the following pre-specified outcomes over a 30-month mean follow-up period:

• Significant reduction in the incidence of non-fatal ischemic major adverse cardiac events (MACE) due to a heart attack (myocardial infarction, MI) or stroke (cerebrovascular accident, CVA) by 60% relative to controls in the total population of 537 patients (p=0.002); reduction in MACE was seen consistently across both New York Heart Association (NYHA) class II or III populations and irrespective of whether the underlying cause of heart failure was ischemic or non-ischemic
• Significant reduction in death from all cardiac causes (CV death) in the 206 heart failure patients with NYHA class II disease by 60% relative to controls (p=0.037), which was evident in both ischemic and non-ischemic subgroups
• Prevention of NYHA class II patients progressing to CV death rates of NYHA class III patients (p=0.004); in contrast, NYHA class II patients on maximal therapy in the control group progressed to CV death rates of NYHA class III patients after a mean period of 20 months of disease stability
• Significant reduction in the composite of the pre-specified CV death or ischemic MACE outcomes in heart failure patients with NYHA class II disease by 55% relative to controls (p=0.009)

“The trial results show that rexlemestrocel-L significantly reduces cardiovascular mortality when used early in heart failure patients at risk of disease progression, and provides durable protection from heart attacks or strokes in these vulnerable patients,” said the trial’s co-principal investigator Dr Emerson Perin, Director of the Center for Clinical Research, Medical Director of Texas Heart Institute, and Clinical Professor, Baylor College of Medicine. “New therapies have not materially reduced the high death rates from cardiovascular disease which is why these data have the potential to change the treatment paradigm for patients with advanced chronic heart failure.”

Mesoblast Chief Medical Officer Dr Fred Grossman said: “We expect the mortality benefit observed in this seminal Phase 3 trial will support a potential path for approval of rexlemestrocel-L in patients with advanced chronic heart failure. We are planning to meet and discuss potential pathways to approval based on mortality reduction with the United States Food and Drug Administration.”

"Fast Track designation by the FDA is intended to facilitate development and expedite review of therapies to treat serious and life-threatening conditions with no or limited treatment options so that an approved product can reach the market expeditiously. Under Fast Track designation, a Biologic License Application (BLA) for remestemcel-L is eligible for both rolling submission and priority review."

This should get MSB 's SP moving back up...

Disc: I hols MSB

MESOBLAST ENTERS GLOBAL COLLABORATION FOR DEVELOPMENT, MANUFACTURE AND COMMERCIALIZATION OF REMESTEMCEL-L

Key transaction terms:

• Novartis will make a US$50 million upfront payment including US$25 million in equity.
• From the initiation of a Phase 3 trial in all-cause ARDS, Novartis will fully fund global clinical development for all-cause ARDS and potentially other respiratory indications.
• Mesoblast may receive a total of US$505 million pending achievement of precommercialization milestones for ARDS indications.
• Mesoblast may receive additional payments post-commercialization of up to US$750 million based on achieving certain sales milestones and tiered double-digit royalties on product sales.
• Mesoblast will retain full rights and economics for remestemcel-L for graft versus host disease (GVHD), and Novartis has an option to, if exercised, become the commercial distributor outside of Japan.
• For most non-respiratory indications, the parties may co-fund development and commercialization on a 50:50 profit-share basis.
• Mesoblast will be responsible for clinical and commercial manufacturing and Novartis will purchase commercial product under agreed pricing terms. Novartis will reimburse Mesoblast up to US$50 million on the achievement of certain milestones related to the successful implementation of its next-generation manufacturing processes using its proprietary media and three-dimensional bioreactors aimed at delivering substantial manufacturing efficiencies. Novartis will be responsible for any capital expenditure required to meet increased capacity requirements for manufacture of remestemcel-L.

Class action launched a few days ago in NY will add to the downward slide I suspect

02-Oct-2020:  Update on BLA for Graft Versus Host Disease

MESOBLAST RECEIVES COMPLETE RESPONSE LETTER FROM THE FDA FOR BIOLOGICS LICENSE APPLICATION FOR STEROID-REFRACTORY ACUTE GRAFT VERSUS HOST DISEASE IN CHILDREN

Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, announced today that the US Food and Drug Administration (FDA) has issued a Complete Response Letter to its Biologics License Application (BLA) for remestemcel-L for the treatment of pediatric steroid-refractory acute graft versus host disease (SR-aGVHD). While the Oncologic Drugs Advisory Committee (ODAC) of the FDA voted 9:1 that the available data support the efficacy of remestemcel-L in pediatric patients with SR-aGVHD, the FDA recommended that Mesoblast conduct at least one additional randomized, controlled study in adults and/or children to provide further evidence of the effectiveness of remestemcel-L for SR-aGVHD.

As there are currently no approved treatments for this life-threatening condition in children under 12, Mesoblast will urgently request a Type A meeting with the FDA, expected within 30 days, to discuss a potential accelerated approval with a post-approval condition for an additional study.

--- click on link above for the remainder of this announcement ---

https://www.asx.com.au/asx/statistics/displayAnnouncement.do?display=pdf&idsId=02289059

Looks like the FDA is asking MSB to run another test, meaning the approval baked into the share price has not been given as expected. 

Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, announced today that the US Food and Drug Administration (FDA) has issued a Complete Response Letter to its Biologics License Application (BLA) for remestemcel-L for the treatment of pediatric steroid-refractory acute graft versus host disease (SR-aGVHD). While the Oncologic Drugs Advisory Committee (ODAC)1 of the FDA voted 9:1 that the available data support the efficacy of remestemcel-L in pediatric patients with SR-aGVHD, the FDA recommended that Mesoblast conduct at least one additional randomized, controlled study in adults and/or children to provide further evidence of the effectiveness of remestemcel-L for SR-aGVHD. As there are currently no approved treatments for this life-threatening condition in children under 12, Mesoblast will urgently request a Type A meeting with the FDA, expected within 30 days, to discuss a potential accelerated approval with a post-approval condition for an additional study.

Joanne Kurtzberg, MD, Jerome Harris Distinguished Professor of Pediatrics, Director, Pediatric Blood and Marrow Transplant Program, and Co-Director, Stem Cell Transplant Laboratory Duke University Medical Center, said: “The Phase 3 trial results showed that remestemcel-L provides a meaningful treatment for children with SR-aGVHD who have a very dismal prognosis. I look forward to having this much-needed therapy available to our patients.”

Mesoblast is currently conducting a randomized, controlled Phase 3 trial evaluating remestemcel-L in up to 300 ventilator-dependent adults with moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19. A second interim analysis by the trial’s independent Data Safety Monitoring Board is expected in early November, with completion of patient enrollment expected in December. COVID-19 ARDS is an inflammatory disease with a similar profile of damaging inflammatory cytokines as is seen in children with SR-aGVHD, and is the primary cause of death in COVID-19 infection. The trial’s primary endpoint is reduction of all-cause mortality within 30 days of randomization.

The FDA also identified a need for further scientific rationale to demonstrate the relationship of potency measurements to the product’s biologic activity. Assays measuring the potency of remestemcel-L will continue to be refined to provide further scientific rationale for its use in severe inflammatory diseases with high mortality risk, such as SR-aGVHD and COVID-19 ARDS.

Mesoblast Chief Executive Dr Silviu Itescu stated: “We are working tirelessly to bring remestemcel-L to patients with life threatening inflammatory conditions, including SR-aGVHD and COVID-19 ARDS.”

MESOBLAST WINS 2020 FIERCE BIOTECH INNOVATION OF THE YEAR AWARD FOR REMESTEMCEL-L

Melbourne, Australia; September 15 and New York; USA; September 14, 2020: Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, today announced that its lead product candidate remestemcel-L has been selected as the winner of the Fierce Innovation Awards - Life Sciences Edition 2020 for Biotech Innovation. The Fierce Innovation Awards is a peer-reviewed program from the publisher of FierceBiotech and FiercePharma.

Mesoblast Chief Executive Dr Silviu Itescu stated: “This important award is recognition of Mesoblast’s leadership as an innovator in the cell therapy industry, and of the potential for remestemcel-L to profoundly impact the lives of children suffering with steroid-refractory acute graft versus host disease (SR-aGVHD).”

Remestemcel-L is under priority review by the United States Food and Drug Administration (FDA) for pediatric SR-aGVHD and, if approved, product launch in the United States is expected in 2020. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of September 30, 2020.

Remestemcel-L is an investigational therapy comprising culture-expanded mesenchymal stem cells derived from the bone marrow of an unrelated donor. It is thought to have immunomodulatory properties to counteract the cytokine storms that are implicated in various inflammatory conditions by down-regulating the production of pro-inflammatory cytokines, increasing production of antiinflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.

Given the extensive inflammatory response in COVID-19 infection, remestemcel-L is also being evaluated in a randomized, controlled Phase 3 trial in up to 300 ventilator-dependent adults with moderate to severe acute respiratory distress syndrome (ARDS), the primary cause of mortality in COVID-19 patients. The trial aims to confirm results from a pilot study at New York’s Mt Sinai hospital which showed that nine of 12 patients (75%) were successfully discharged from hospital a median of 10 days after receiving two intravenous doses of remestemcel-L within five days. The trial’s independent Data Safety Monitoring Board (DSMB) recently completed an interim analysis of the trial’s first 30% enrolled patients and recommended that the trial should continue as planned after reviewing all safety data and results for the trial’s primary endpoint of all-cause mortality within 30 days of randomization. The DSMB will perform a second interim analysis when 45% of the enrollment target has completed 30 days of follow-up.

06-May-2020:  First Patients Dosed in Phase 2/3 Trial for COVID-19 ARDS

09-Apr-2020:  US NIH Trials Network to Conduct COVID-19 Phase 2/3 Trial

MSB is up another +21% today on the back of this announcement, on top of the +35% rise they enjoyed on Monday.