MSB announced an addition to their BOD.  He is the Chief Strategy officer of SurgiCenter is one of the largest private operators of ambulatory surgical centers (ASC) in the US specializing in spine, orthopaedic and total joint procedures. Theprincipals of SurgCenter were the lead investors in Mesoblast’s successful US$110 million private placement, completed earlier this month.   He said, "My fellow principals at SurgCenter and I are very excited about the future potential for Mesoblast across the breadth of its platfo rm technology from chronic heart failure and inflammatory bowel disease to the potential treatment for chronic low back pain. I welcome the opportunity to make a significant contribution to the success in bringing these potential treatments to market and look for ward to working with the Board and management team.” 

This is the area MSB needs the most help as they have yet to clear any FDA hurdle placed before them.  This new investor believes in numerous therapies MSB has to offer and hopefully can bring the necessary skills to get them to market.  As a long time holder, I sure hope so.

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 ---

Mesoblast Limited

The share price of Mesoblast Limited (ASX: MSB) edged up by around 46% in the past one month and 65.5% in the last six months. The recent MSB stock movement suggests that $10,000 investment in its shares one month back would now have been $14,600. The significant popularity of MSB shares is riding on the back of its latest endeavours in Covid-19 vaccine development. Significantly, MSB stock closed at $4.910 per share on 17 August 2020, up by over 4.468% intraday. 

In the latest update, Mesoblast indicated Oncologic Drugs Advisory Committee (ODAC) of the United States Food and Drug Administration (FDA) voted in great majority in favour of Remestemcel-L (RYONCIL™) for its efficacy in pediatric patients with Steroid-refractory Acute Graft Versus Host disease. 

The Company’s lead product candidate, RYONCIL (remestemcel-L), is an investigational therapy, which comprises of culture-expanded mesenchymal stem cells that are derived from an unrelated donor’s bone marrow and administered in a series of infusions. 

ALSO READ: Mesoblast Share Price Goes Berserk: Investors had a Sunny Day

RYONCIL - down-regulates pro-inflammatory cytokines production, increases anti-inflammatory cytokines production and enables recruitment of naturally occurring anti-inflammatory cells to involved tissues. RYONCIL believed to have immunomodulatory properties and uses the above process to counteracts the inflammatory processes that are implicated in steroid-refractory acute graft versus host disease.  

The outlook for Mesoblast includes:

• Biologics License application of Mesoblast seeking the approval for its product candidate RYONCIL™ for steroid-refractory acute graft versus host disease in children has been accepted for priority review by FDA. If approved, the product is expected to be launch in the US in 2020. 
• Remestemcel-L for other inflammatory diseases in children and adults is also being developed by the Company and includes moderate to severe acute respiratory distress syndrome.
• Mesoblast is completing phase 3 trials for its product candidates for advanced heart failure and chronic low back pain. 

Late to this, but it's surprising how blindsided many capable investors were by the resounding FDA Advisory Committee support for Ryoncil. As mentioned previously, Priority Review almost always ends up in approval (base rates, baby), and anyhow one of Mesoblast's usurers-of-last-resort had effectively made interest repayments contingent on approval (repayments only kicked in once US and European sales began). Lenders with 10%+ interest rates don't usually indulge desperate crapcos out of the goodness of their hearts. Moreover, the FDA briefing document was only about as adversarial as recent similar ones for treatments that were eventually approved.

From here, though, it's not clear to me what new buyers of the stock expect to see happen. Approval for Ryoncil’s tiny market does probably make it easier for Mesoblast to get approvals for wider applications and for other treatments too. But much of the market cap depends on a COVID treatment for which there is currently almost no evidence available. If the COVID trial goes belly-up, or the overdue Phase III trials come back with bad news, or the FDA decides to ask for more data there is plenty of downside in the current share price. An added problem is that in October - originally July but then the COVID news magically saved the day - Mesoblast needs to start paying back the very large principal to its other lender.

Disc: Sadly I sold as soon as the FDA briefing document was published, not having time that day to weight it up properly. I just couldn’t deal with the risk anymore, the latest red flag being the longstanding major shareholder selling down, a sale that has continued since. But as ever, taking profits can be where you lose the most money. Chalk this one up to bitter experience.

Today's news of a 9 to 1 vote in favour of MSB's candidate for aGVHD by the ODAC further de-risks investment in the company and helps validate their core technology which they hope to apply to many on the major health concerns of today, including COVID 19.

U.S. FDA ADVISORY COMMITTEE VOTES NINE TO ONE IN FAVOR OF REMESTEMCEL-L (RYONCIL™) FOR EFFICACY IN CHILDREN WITH STEROIDREFRACTORY ACUTE GRAFT VERSUS HOST DISEASE

Mesoblast Limited (ASX:MSB; Nasdaq: MESO), global leader in cellular medicines for inflammatory diseases, today announced that the Oncologic Drugs Advisory Committee (ODAC) of the United States Food and Drug Administration (FDA) voted overwhelmingly in favor that the available data support the efficacy of remestemcel-L (RYONCIL™) in pediatric patients with steroid-refractory acute graft versus host disease (SR-aGVHD).

Mesoblast Chief Medical Officer Dr Fred Grossman said: “Steroid-refractory acute graft versus host disease is an area of extreme need, especially in vulnerable children under 12 years old where there is no approved therapy. We are very encouraged by today’s outcome and are committed to working closely with the FDA as they complete their review of our submission regarding approval of RYONCIL for this life-threatening complication of an allogeneic bone marrow transplant.”

The ODAC is an independent panel of experts that evaluates efficacy and safety of data and makes appropriate recommendations to the FDA. Although the FDA will consider the recommendation of the panel, the final decision regarding the approval of the product is made solely by the FDA, and the recommendations by the panel are non-binding. RYONCIL has been accepted for Priority Review by the FDA with an action date of September 30, 2020, under the Prescription Drug User Fee Act (PDUFA). If approved by the PDUFA date, Mesoblast plans to launch RYONCIL in the United States in 2020.

Pediatric transplant physician Dr Joanne Kurtzberg, the Jerome Harris Distinguished Professor of Pediatrics and Professor of Pathology, and Director, Pediatric Blood and Marrow Transplant Program at Duke University Medical Center, said: “This devastating condition has an extremely poor prognosis and there are no FDA-approved options for children under the age of 12. The clinical studies I have directed have demonstrated the potential for this treatment to fill a significant unmet medical need.”

14/8 future price loaded up 18% at $4 before open

https://www.afr.com/markets/equity-markets/mesoblast-scores-us-regulatory-breakthrough-20200813-p55lhf

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

Yesterday and overnight Mesoblast's share price had another of its big recent spikes, going up 40% on the ASX and then 140% on NASDAQ. That's effectively another $1.4bn of market cap. The NASDAQ price is higher than it has been since 2015.  

Like the other spikes this one followed a press release. Unlike them the press release conveyed nothing of consequence. Two samples of a dozen COVID-19 patients treated with Mesoblast's remestemcel-L had sharply different outcomes from those for two samples of a few hundred COVID-19. Mesoblast's CEO called this "remarkable". Actually the remarkable thing would have been if the outcomes were in any way similar. In statistical terms this is, to quote Arrested Development, comparing apples with some fruit no one ever heard of. Never mind that almost any mortality rate would have been better than the control group's, or that "patients received a variety of experimental agents prior to remstemcel-L". The COVID-19 results were encouraging rather than "remarkable", just as other preliminary results have been encouraging for therapies that now look like duds (remdesivir, hydroxychloroquine). Might work, might not.

I don't know if management had an obligation to disclose, but if they didn't then it makes you wonder about their mentality. And they certainly didn't have call the findings "remarkable". This is a company that should be on the cusp of at least one big catalyst. The share price can take care of itself. But you'd also think the directors would be buying, and that isn't really happening either. It's puzzling. Treating COVID-19 isn't even part of any long thesis for them, so why hype something that doesn't really demonstrate they can treat it? How will all those traders and first-level MOMO/FOMO punters who have been jumping on the bandwagon like it's January again react to any kind of blip?

Full disclosure: I bought a tiny amount of Mesoblast shares earlier this week. But that's for another post. 

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.

The Vice Chairman (William Burns) doubled his shareholding this week with a purchase on-market of ~33,000 shares at $1.83. The Directors at MSB are not an active bunch and while collectively they hold ~15% of stock, roughly 14.5% is held by a single Director; Silviu Itescu.

The purchase still represents a solid buy with a value of ~$50k, but difficult to say whether this is a bullish sign. If you read through the fine print of the latest annual report you will find a note that William held ~80,000 options expiring November 2019 at an exercise price of $4 per share. So whether the buy is a bullish sign or just a Director trying to hold a bit of skin in the game...will wait to see if other Directors pop their heads up.