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MSB's share price was cut in half on August 4th by the announcement that they needed to do more work in regards their FDA resubmission 05sb7mjzh4lq3w.pdf (asx.com.au)
Since then, they have been working toward approval of their graft vs host disease treatment but need more cash.
Trading halt today for a cap raise, rumoured to be at 30c, a steep discount to last traded price of 40.5c. This is because it is a massive capital raise and will likely anchor the share price to the raise price for a while to come.
They seemed so close to approval but new drug development is full of risks like this, even for good candidates.
Should be good buying around, or even under 30c. One to stick in the bottom drawer because it will re-rate strongly on favourable news.
CHILDREN TREATED WITH REMESTEMCEL-L SHOW LONG-TERM SURVIVAL THROUGH FOUR YEARS IN STEROID-REFRACTORY ACUTE GRAFT VERSUS HOST DISEASE (SR-aGVHD)
The BLA Resubmission is expected before the end of 2022 . Next year will be either a great year for MSB or another year of smoke and mirrors by SI.
SINGLE INTERVENTION WITH REXLEMESTROCEL-L IMPROVES LEFT VENTRICULAR EJECTION FRACTION AT 12 MONTHS, PRECEDING LONG-TERM REDUCTION IN MAJOR ADVERSE CARDIOVASCULAR EVENTS
Mesoblast Limited today announced that treatment of HFrEF patients with rexlemestrocel-L, its allogeneic “off-the-shelf” product candidate for the treatment of chronic heart failure with reduced ejection fraction, resulted in greater improvement in the pre-specified analysis of left ventricular ejection fraction at 12 months relative to controls in the DREAM-HF Phase 3 trial. Improvement in LVEF was most pronounced in the setting of inflammation and preceded long-term reduction in the 3-point MACE of cardiovascular death, non-fatal heart attack or stroke. These results were recently highlighted in a heart failure panel discussion titled “Late-Stage Advancements in Heart Failure Therapeutics and Management.”
Rexlemestrocel-L is an immunomodulatory therapy developed to target the high degree of inflammation and resultant endothelial dysfunction present across the spectrum of HFrEF, from NYHA class II through end-stage CHF on LVADs. This MOA is postulated to improve systolic function and LVEF in HFrEF patients and reduce the high rate of major cardiovascular events and complications, notably 3-point MACE in NYHA class II/III patients and gastrointestinal (GI) tract ischemia, abnormal GI blood vessels, and life-threatening GI bleeding events in LVAD patients. Rexlemestrocel-L has already been granted FDA RMAT and Orphan Drug designations for treatment of chronic heart failure with left ventricular systolic dysfunction in patients with an LVAD.
Results from two large placebo-controlled randomized studies in patients with HFrEF, a disease associated with inflammation, a 565-patient trial in NYHA class II/III patients (DREAM-HF) and a 159patient trial in end-stage heart failure patients implanted with an LVAD, as well as in an earlier 30patient trial in LVAD patients, provide support for a common MOA for rexlemestrocel-L across the spectrum of HFrEF. New data from the DREAM-HF trial shows that a single intervention with rexlemestrocel-L resulted in improvement from baseline to 12 months in LVEF, which preceded and correlated with long-term reduction in MACE across a mean follow up of 30 months. This suggests that early improvement in LV systolic function, as measured by LVEF change from baseline to 12 months, could be an appropriate surrogate endpoint predictive of adverse long-term clinical outcomes in this patient population.
MSB has lifted this morning on the back of the announcement, trading at 94.5 cents (up 10.53%).
Novartis has cancelled its agreement with Mesoblast. The agreement was for a planned investment and commercialisation deal that Mesoblast had said could be worth as much as $US505 million.
The share price of Mesoblast has hit a low of $1.335 this morning, which is the lowest price MSB has been since the COVID market correction of March 2020.
UPDATE ON NOVARTIS AGREEMENT
Melbourne, Australia; December 14, and New York, USA; December 13, 2021:
Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, was notified today by Novartis that it has chosen to terminate the agreement with Mesoblast prior to closing. Mesoblast remains highly focused on executing on our short term objective to bring remestemcel-L to market for patients with acute respiratory distress syndrome (ARDS) due to COVID19.
The observed mortality reduction with remestemcel-L in patients aged under 65 in the completed COVID ARDS trial, despite having missed the primary endpoint, is considered by Mesoblast to be a sufficiently strong signal to support pursuing an emergency use authorization (EUA), the most direct path to market. Mesoblast is preparing to initiate a pivotal Phase 3 trial that may support a COVID ARDS EUA.
COVID-19 is likely to remain a serious global problem and to provide a major commercial opportunity for Mesoblast, with a steady state of intensive care unit (ICU) ARDS patients irrespective of vaccines and anti-viral treatments. Variants including Omicron present a growing threat due to increased infectivity and immune evasion from vaccines and monoclonal antibodies, increasing the urgent need for therapeutics to prevent the likely high mortality of those progressing to ICU and ARDS.
Well this announcement will just add to MSB's yearly interest bill. As @Noicewon11 wrote recently: I'm of the belief that MSB will never make a profit. They've been operating as a listed company for circa 17 years and haven't managed to make a cent of earnings in that time.
With so much debts owing, is this borrowing more to kick the can further down the road?
Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, today announced that it has successfully refinanced its existing senior debt facility with a new US$90 million five year facility provided by funds managed by Oaktree Capital Management, L.P. (“Oaktree”).
Mesoblast drew the first tranche of US$60 million on closing, with proceeds being used to repay the outstanding balance of the existing senior debt facility with Hercules Capital, Inc. Up to an additional US$30 million may be drawn on or before December 31, 2022, subject to certain milestones. The facility has a three-year interest only period, at a rate of 9.75% per annum, after which time 40% of the principal amortizes over two years and a final payment due November 2026. Oaktree will also receive warrants to purchase 1,769,669 American Depositary Shares (ADSs)1 at US$7.26 per ADS, a 15% premium to the 30-day VWAP. The warrants may be exercised within 7 years of issuance.
“We are pleased to have leading global investment management firm Oaktree as our new financing partner as we focus on bringing our first product to the US market. Oaktree has a demonstrated partnership approach to innovative companies, making it an excellent fit to support Mesoblast’s commercial growth strategy over the next five years,” said Silviu Itescu, Chief Executive of Mesoblast.
Aman Kumar, Co-Portfolio Manager of Life Sciences Lending at Oaktree said, “We are delighted to partner with Mesoblast at this point in its development. We recognize the quality of the portfolio and the significant near-term milestones that could help the company successfully commercialize its first product in the US.” Cantor Fitzgerald & Co. acted as exclusive arranger and financial advisor to Mesoblast in this transaction.
As usual, MSB update the market with the standard news (see yellow).
Cudos to arguably the worst company on the ASX.
If you own this business then I must ask what the thesis could possibly be
Impending capital raise/debt raising incoming....
Mesoblast Operational and Financial Highlights for Quarter Ended June 30, 2021
Melbourne, Australia; July 30 and New York, USA; July 29, 2021: Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, today provided an update on its pipeline of late-stage product candidates, and an activity report for the fourth quarter ended June 30, 2021. “During the quarter we made significant progress in both regulatory and clinical outcomes for our lead product candidate, remestemcel-L. FDA’s CBER has recently recommended the next steps in the potential approval pathway for remestemcel-L in the treatment of steroid-refractory acute graft versus host disease in children” said Silviu Itescu, Chief Executive of Mesoblast. “Additionally, as COVID infections continue to surge, the 90-day survival outcomes from the remestemcel-L trial in adults with COVID ARDS demonstrated the potential for durable benefit of this therapy in certain segments experiencing the most extreme complication of this disease.”
Key operational highlights:
- Mesoblast met with the United States Food & Drug Administration (FDA) on potential pathways to regulatory approval of its lead technology platform product remestemcel-L for steroid refractory acute graft versus host disease (SR-aGVHD) in children and acute respiratory distress syndrome (ARDS) in adults with COVID-19
- Regarding SR-aGVHD, FDA’s Center for Biologics Evaluation and Research (CBER) recommended that Mesoblast as a next step discuss with CBER’s review team at the Office of Tissue and Advanced Therapies (OTAT) our approach to address certain outstanding chemistry, manufacturing and controls (CMC) items, including potency assays, which could support a resubmission of the current Biologic License Application (BLA) with a six-month review period
- Regarding COVID ARDS, Mesoblast met with the FDA this week to determine the registration pathway for approval of remestemcel-L in this indication, with formal minutes expected in coming weeks
- Results from the randomized controlled trial of remestemcel-L in 222 ventilator-dependent COVID-19 patients with moderate/severe acute respiratory distress syndrome (ARDS) were recently highlighted at the biennial Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases conference hosted by the University of Vermont, Burlington, VT, and at the International Society for Cell & Gene Therapy (ISCT) Scientific Signatures Series event on Cell and Gene-Based Therapies in Lung Diseases and Critical Illnesses
- The presented data included improved respiratory function in patients treated with remestemcel-L, as well as 90-day survival outcomes showing remestemcel-L significantly reduced mortality by 48% at 90 days compared to controls in a pre-specified analysis of 123 treated patients under 65 years old
- Mesoblast has entered into a license and collaboration agreement with Novartis for the development, manufacture, and commercialization of remestemcel-L, with an initial focus on the treatment of acute respiratory distress syndrome (ARDS), including that associated with COVID-19. The agreement remains subject to certain closing conditions, including time to analyze the results from this COVID-19 ARDS trial
- Mesoblast filed requests and expects to hold meetings with the FDA during the next two quarters to discuss the pathways to US regulatory approvals for its second technology platform rexlemestrocel-L following the recently completed Phase 3 trials in patients with chronic heart failure and chronic inflammatory back pain due to degenerative disc disease
- Mesoblast and its partner in Europe and Latin America, Grünenthal, amended their collaboration agreement in line with a strategy to achieve regulatory harmonization, cost efficiencies and streamlined timelines aiming to leverage the results from a planned US trial in support of potential product approvals in both US and EU
Behind the Mask of Mesoblast Highlights:
Share price
Over the past year the MSB share price has been fluctuating massively for a company with a $1.3 Billion Market Cap. Today the Share price is $1.89 after a further 2.33% drop. Over 12 months the stock price is down 48.64%. Over the course of five years the price has remained stagnant.
Yesterday mesoblast released an announcement of their journal article, which was published in the medical journal BMC. This was titled “Effect of mesenchymal stromal cell infusions on lung function in COPD patients with high CRP levels”
Mesoblast Shares: COVID Play
Mesoblast has found their products Remestemcel-L reduces the mortality rate of COVID patients with moderate to severe ARDS (Acute Respiratory Distress Syndrome).
Not only was it found to reduce mortality but also lead to increased days alive off
mechanical ventilation and reduced days in hospital. These factors alone could take a large burden on the cost and availability of healthcare.
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 ---
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.
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.
MESOBLAST REPORTS SUBSTANTIAL OPERATIONAL PROGRESS AND FINANCIAL RESULTS FOR THE YEAR ENDED JUNE 30, 2020
Financial Highlights
- 92% increase in revenues to US$32.2 million for FY2020, compared with US$16.7 million for FY2019. o 127% increase in milestone revenue from strategic partnerships, to US$25.0 million for FY2020. o 32% increase in royalty revenue on TEMCELL® HS. Inj.1 sales in Japan by licensee JCR Pharmaceuticals (JCR), to US$6.6 million for FY2020.
- 13% reduction in loss after tax (US$77.9 million for FY2020 compared with US$89.8 million for FY2019), even after US$13.8 million increased investment in commercial readiness for the potential US launch of RYONCIL (US$8.8 million for commercial manufacturing activities and US$5.0 million for sales/marketing).
- US$129.3 million (A$188.4 million)2 cash on hand at June 30, 2020, after US$90 million (A$138 million)3 capital raise from global institutional investors in May 2020.
- May have access to up to an additional US$67.5 million over the next 12 months through existing financing facilities and strategic partnerships.
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
Request for trading halt for Mesoblast Limited (ASX: MSB)
Pursuant to ASX Listing Rule 17.1, Mesoblast Limited ACN 109 431 870 (ASX: MSB; NASDAQ: MESO) (the Company) requests a trading halt in its securities effective immediately pending an announcement by the Company in relation to the upcoming meeting of the Oncologic Drugs Advisory Committee of the United States Food and Drug Administration.
For the purposes of Listing Rule 17.1, the Company provides the following information:
(a) the trading halt is requested pending an announcement in relation to the matters above;
(b) the Company requests that the trading halt continues until it makes an announcement regarding the matters above which is expected to be on Friday, 14 August 2020; and
(c) the Company is not aware of any reason why the trading halt should not be granted or of any other information necessary to inform the market about the trading halt.
UPDATE ON SCHEDULED FDA ADVISORY COMMITTEE MEETING
Melbourne, Australia; August 11, 2020; and New York, USA; August 10, 2020: Mesoblast Limited (ASX:MSB; Nasdaq:MESO) today provided an update on the scheduled meeting of the Oncologic Drugs Advisory Committee (ODAC) of the United States Food and Drug Administration (FDA) which will review data supporting the Company’s Biologics License Application (BLA) for approval of RYONCIL™ (remestemcel-L) in the treatment of steroid-refractory acute graft versus host disease (SR-aGVHD) in children. There are currently no FDA-approved treatments in the United States for children under 12 with SR-aGVHD, a potentially life-threatening complication of an allogeneic bone marrow transplant for blood cancer.
The meeting is scheduled to take place on August 13, 2020 from 8am to 5pm ET. The ODAC will vote in the afternoon session on whether the available data support the efficacy of remestemcel-L in pediatric patients with SR-aGVHD. This session will discuss the Phase 3 trial results and supporting clinical data included in the BLA. The morning session will be non-voting and will discuss issues related to the characterization and critical quality attributes of remestemcel-L.
Mesoblast has extensively prepared for this meeting and has provided a publicly available briefing book. Briefing materials and webcast information have been made publicly available and can be found on the FDA website at: https://www.fda.gov/advisory-committees/advisory-committeecalendar/august-13-2020-meeting-oncologic-drugs-advisory-committee-meeting-announcement08132020-08132020#event-materials
The ODAC is an independent panel of experts that provides advice and appropriate recommendations to the FDA based on potential issues highlighted by the FDA during their review of the efficacy and safety of marketed and investigational products for use in the treatment of cancer. Although the FDA will consider the recommendation of the advisory committee, the final decision regarding the approval of the product is made by the FDA solely, and the recommendations by the panel are non-binding.
RYONCIL is under Priority Review by the FDA with an action date of September 30, 2020, under the Prescription Drug User Fee Act (PDUFA).
FDA ADVISORY COMMITTEE SETS REVIEW DATE FOR MESOBLAST’S REMESTEMCEL-L IN PEDIATRIC STEROID-REFRACTORY ACUTE GRAFT VERSUS HOST DISEASE
Mesoblast Limited (ASX:MSB; Nasdaq:MESO) today announced that the Oncologic Drugs Advisory Committee (ODAC) of the United States Food and Drug Administration (FDA) has scheduled a meeting on August 13, 2020 to review data supporting the Company’s Biologics License Application (BLA) for approval of RYONCIL™ (remestemcel-L) for the treatment of steroid-refractory acute graft versus host disease (SR-aGVHD) in children.
There are currently no FDA-approved treatments in the United States for children under 12 with SRaGVHD, a potentially life-threatening complication of an allogeneic bone marrow transplant for blood cancer. RYONCIL is under Priority Review by the FDA with an action date of September 30, 2020, under the Prescription Drug User Fee Act (PDUFA).
The ODAC is an independent panel of experts that provides advice and appropriate recommendations to the FDA based on potential issues highlighted by the FDA during their review of the efficacy and safety of marketed and investigational products for use in the treatment of cancer. The ODAC review will comprise two separate sessions: a morning session which will discuss issues related to the characterization and critical quality attributes of remestemcel-L as they relate to clinical effectiveness, and an afternoon session which will discuss results from clinical trials included in the BLA.
Although the FDA will consider the recommendation of the panel, the final decision regarding the approval of the product is made by the FDA solely, and the recommendations by the panel are nonbinding.
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.
06-Apr-2020: FDA Clears IND for Remestemcel Use in COVID-19 ARDS
14:15 (2:15pm Sydney Time): MSB is up around +35% today on the back of that one.
Completed recruitment in their phase 3 heart failure trial. Is the company better today than yesterday - no... but is much closer to a potentially massive catalyst.
heart failure isnt like gvhd where msb is likely to gain fda approval... as a condition, it is very very common and thus the potential opportunity is huge - but this comes with a big if... the primary endpoint is met
this is a gamble, but as i see it, the trial is either positive in which case msb may well be worth a magnitude of times more than it currently is... or it fails and the indication isnt successful in which case the share price would drop and still represent a reasonable buying opportunity given the gvhd indication looks likely and theres several other trials underway
lots of ways to win very very big, minimal losses (in the longterm) except for wasted cash funding trials
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.
"I am not smart man" said Forest Gump...me either! I don't have the intelligence or the time to review, research and understand winners and losers in bio-tech. I would challenge any investor that thinks they understand the technology, or the science...I certainly don't! So why do I like Mesoblast? Because...people who are smarter than me, have more resources than me, and who pay other smart people to research whether the technology and science works...they like Mesoblast!
Rich lister and technology investor Alex Waizlits is a large holder of Mesoblast and has been for some time through both his privately owned fund (Thorney Investment Group) and also his public fund (Thorney Technologies). I think taken together the two entities own approximately 10% of Mesoblast.
In addition to the fact that someone much smarter than me is heavily invested, I like the amount of time he has been invested. This says to me this is a conviction play and that the potential return is worthwhile having your cash held up for years.
This article references his purchase of ~$67 million in Mesoblast back in April 2015: http://www.medifydaily.com.au/waislitz-emerges-with-mesoblast-stake-worth-67-3m/
In this more recent article he continues to talk up the potential: https://www.afr.com/leadership/afr-lists/rich-list/how-the-rich-invest-alex-waislitz-shares-his-stock-tips-20181004-h1682o
Sometimes it's ok to put your faith in the ability of others...particularly when their own money is in play!
Recent release of 180day mortality rate in gvhd paedeatric study of 69% which seems fairly impressive considering many of the children had the most severe gvhd. This compares with expected survival of <30%. This was a phase 3 study.
already has sales in Japan and likely to extend slsewhere. Although i would expect they will charge a significant cost for their medication, it is likely that for a treatment that improves survival after transplantation in sick children with cancer that they will likely get approval from funders.
Valuation somewhat difficult, particularly if their heart failure trials are +.
I decided on a lazy sunday morning that having a valuation of $10 per share on a company currently valued around $1.40 with little or no reason for the valuation was a bit silly. So with that in mind I did some homework and came up with an even sillier valuation with some data to back it up....and I got a value of $32 per share....and thought that's crazy (?) you idiot (!) check the NPV calculation...which I did, and surely enough found a mistake, corrected it....and got a value per share of $105. Much better!
In 12 months time I will look back and try and decide which of the following has been the lesson learnt:
1. Valuing the future cash flows of an early stage bio tech company is stupid - why bother when it is all 100% made up!?
2. Valuing the future cash flows of an early stage bio tech company is interesting as it shows the potential size of the prize.
I have no doubt that there are a million things that are wrong with my valuation. Even looking at the numbers and estimating revenue of $40 billion per annum for the heart failure solution seems ridiculous...but saying that the problem costs the US $115 billion every year...so maybe it isn't crazy.
Really who the hell knows!
The recent announcement that MSB have formed a strategic partnership with Grünenthal for chronic lower back pain is potentially the first of many to come which would result in a significant rerate of MSB's value.
Mesoblast has released a ‘Corporate Review’ (three-page newsletter) detailing the major commercial focusses for the business in 2019.
- The company has a product gaining traction under licence in Japan and proving the case for Mesoblast to launch solo in the US in 2019.
- They are in advanced and active discussions with a number of partners for global commercialisation of their products.
- Also, the letter makes clear that they have enough of cash to meet their key commercial outcomes and access to additional funding that is ‘nondilutive’.
All great stuff, right…but nothing new. The commercial opportunities outlined, these are all generally well known. The company has previously advised that they are in commercial negotiation with potential global partners (to be honest most investors are probably a bit peeved that it is taking so long). There was no new price sensitive information contained in the letter, and yet the share price reacted strongly, jumping 15% on the day.
I think investors have reacted to a more holistic element of the letter than its contents; its tone. Historically Mesoblast has not focussed on its investors, it has focussed on the science. Releasing a note that focusses on the potential catalysts for success in 2019 is breaking new ground and creates a feel that success is inevitable. Did someone say FOMO…
I love a conspiracy theory and I wonder why the change of tone? If one of the global partnerships talked about takes off in H1-2019 then I think a capital raise is unlikely, but if we don’t see one then I think a capital raise may be necessary in late 2019 regardless of meeting key commercial outcomes. Time for management to start pumping up the tyres?
Despite my suspicions I liked the newsletter and I think 2019 will be a good year.
Phase 3 trial failure can impart a death blow. Why? Because the company's share price is near historic lows and this means equity raise will be even more dilutive post any failure. Further, the market has doubts about the company's programs because Teva pulled out of sponsoring the heart failure treatment (it was a partner via purchase of Cephalon); Teva also sold out of its stake in Mesoblast. Now the market I am hypothesing has taken that to mean that Teva knows something more than what has been publicly disclosed but I believe the reality is elsewhere. Teva itself has made a bunch of acquisitions in its attempt to become a generic drugs leader and as a result it has to optimise its portfolio, more so in the context of its multi-billion dollar purchase of Allergan. Post the Allergan acquisition Teva has been busy paring back debt.
But a botched NASDAQ listing and the pullout of Teva has knocked the sails out of Mesoblast's share price. That, in turn, has made raising cash and partnership deals harder. I believe minor holders like Celgene are in a wait and watch mode. If one of the phase 3 trials demonstrate further positive results I believe US giants like Celgene will make a move.
Nonetheless, development stage biotechs are money sinks. They need lots of cash to keep their programs running and Mesoblast is in a situation where a stumble won't be pretty.
Mesoblast has one of the most advanced cellular therapy platforms in the world. IThe key IP concerns the use of Mesenchymal Lineage Cells (MLCs) which have unique receptors that respond to activating inflammatory and damaged-tissue signals. t's pioneering MLC-based allogenic stem cell treaments where the idea is to harvest stem cells from donors to mass produce treatments for ailments. These "off the shelf" product candidates can in theory be mass produced.
The company already has a treatment for actute GVHD approved in Japan. It is currently running phase 3 trials for approval of the same treatment in the US.
In addition, Mesoblast has two other products in phase 3 trials in the US, one for advanced/end-stage heart failure and another for chronic backpain.
The GVHD opportunity is modest but a good step towards getting a foothold for MLC treatments in the US. The bigger opportunities are in the backpain and heart failure markets. In the US alone, chronic heart failure related healthcare costs are estimated to be about US$ 60 billion annually.
In the near-term, partnering opportunities can give a boast and provide much needed cash for bolestering the trial programs and starting commercialisation plans. If the company is successful with either backpain or heart failure programs, it would command a market capitalisation of at least an order of magnitude greater than it's current market cap.
Mesoblast is a high risk, high reward opportunity.
Post a valuation or endorse another member's valuation.