Washington, D.C. 20549

 Form 6-K

Report of Foreign Private Issuer
Pursuant to Rule 13a-16 or 15d-16 under the Securities Exchange Act of 1934

For the month of September 2019

Commission File Number 001-37626

Mesoblast Limited

(Exact name of Registrant as specified in its charter)

Not Applicable

(Translation of Registrant’s name into English)

Australia
(Jurisdiction of incorporation or organization)

 

Silviu Itescu

Chief Executive Officer and Executive Director

Level 38

55 Collins Street

Melbourne 3000

Australia

(Address of principal executive offices)

 

Indicate by check mark whether the registrant files or will file annual reports under cover Form 20-F or Form 40-F:

Form 20-F ☑ Form 40-F ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):

Yes ☐ No ☑

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7):

Yes ☐ No ☑

 

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INFORMATION CONTAINED ON THIS REPORT ON FORM 6-K

On September 10, 2019, Mesoblast Limited filed with the Australian Securities Exchange a new release announcement and investor presentation, which are attached hereto as Exhibit 99.1 and Exhibit 99.2, and are incorporated herein by reference.

 

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SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly organized.

Dated: September 11, 2019

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INDEX TO EXHIBITS

 

 

Exhibit 99.1

 

Grünenthal and Mesoblast Enter Strategic Partnership for Europe and Latin America to Develop and Commercialise Innovative Cell Therapy for the Treatment of Chronic Low Back Pain

 

Aachen, Germany, and Melbourne, Australia, 10 September 2019 – Grünenthal, a global leader in pain management, and Mesoblast Limited (ASX: MSB; Nasdaq: MESO), a world leader in allogeneic cellular medicines for inflammatory diseases, today announced that they have entered into a strategic partnership to develop and commercialise MPC-06-ID, a Phase III allogeneic cell therapy candidate for the treatment of chronic low back pain due to degenerative disc disease in patients who have exhausted conservative treatment options. Under the partnership, Grünenthal will have exclusive commercialisation rights to MPC-06-ID for Europe and Latin America. 

 

Mesoblast will receive up to US$150 million in upfront and milestone payments prior to product launch, as well as further commercialisation milestone payments. These payments include commitments up to US$45 million within the first year comprising US$15 million on signing, US$20 million on receiving regulatory approval to begin a confirmatory Phase III trial in Europe, and US$10 million on certain clinical and manufacturing outcomes. Cumulative milestone payments could exceed US$1 billion depending on the final outcome of Phase III studies and patient adoption. Mesoblast will also receive tiered double digit royalties on product sales.

 

Mesoblast is completing a Phase III trial for MPC-06-ID in the U.S. which will read out in 2020. In a previous U.S. Phase II trial, Mesoblast demonstrated that a single intra-discal injection of MPC-06-ID using a unit dose of 6 million allogeneic mesenchymal precursor cells (MPCs) resulted in meaningful and durable improvements for patients in pain intensity and functionality for at least three years¹. 

 

Grünenthal and Mesoblast have agreed on an overall development plan for MPC-06-ID to meet European regulatory requirements. As part of this plan, the companies will collaborate on the study design for a confirmatory Phase III trial in Europe. The results of the two Phase III trials are expected to support both U.S. FDA and European EMA regulatory approvals for MPC-06-ID in chronic low back pain due to degenerative disc disease.

 

 

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Grünenthal’s CEO Gabriel Baertschi said: “This is an exciting day for Grünenthal. Cell-based therapies offer a novel approach in pain management. They can potentially deliver meaningful lasting improvements to patients beyond symptomatic treatment by maintaining or even restoring physiological function. By teaming up with Mesoblast for the next generation of pain therapies for chronic low back pain due to degenerative disc disease we are diligently executing our strategy: leveraging promising new therapeutic modalities and addressing patients with high unmet medical needs. This is an important next step in working towards our vision of a world free of pain.”

 

Mesoblast Chief Executive Dr Silviu Itescu stated: “We are very pleased to enter into this strategic partnership with Grünenthal, a world leader in innovative approaches to pain management. Together with Grünenthal we plan to bring an important new class of therapy for pain management to the many patients suffering with degenerative disc disease. This partnership is in line with our corporate strategy to team up with best in category commercial leaders to maximise market access for our innovative cellular medicines for the treatment of patients suffering from debilitating or life-threatening inflammatory conditions.”

 

MPCs have generated great interest in clinical science and medicine due to their immunomodulatory effects and their role in tissue repair and regeneration. These cells have been shown to be effective in reducing inflammation and promoting the regeneration of host tissues through cell-to-cell interactions and secretion of a wide range of endogenous analgesic and anti-inflammatory molecules^2,3. Furthermore, in degenerative disc disease, these cells could contribute to regenerating physiological disc tissue by promoting the proliferation of host chondrocytes and their secretion of tissue matrix components⁴.  Among key characteristics of MPCs are their capacity for significant expansion in culture and their relative lack of immunogenicity.  These properties facilitate their use as allogeneic, or “off-the-shelf”, therapeutics with well-defined release criteria and batch-to-batch reproducibility that meet stringent regulatory requirements.  

 

About Chronic Low Back Pain due to Degenerative Disc Disease (CLBP)

Over 7 million patients in Europe are thought to suffer from CLBP caused by degenerative disc disease^5,6,7,8, a disease which involves inflammation and degeneration of the intervertebral discs due to various factors like age, trauma or genetic pre-disposition. The lack of ‘cushioning’ as one of the major physiological functions of the disc in turn can result in spinal instability,

 

 

 

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mechanical stress and bony changes of the spine which finally cause significant pain and loss of function⁹. In addition, the inflammation of the disc can cause severe pain, which is poorly responsive to systemic pain treatment¹⁰. Most existing therapies do not address the underlying mechanisms of these changes and provide limited symptomatic relief. Patients would typically suffer for several years already at a relatively young age, without being able to sufficiently address their pain¹¹. Invasive therapies, including surgeries like spinal fusion, are sometimes a last resort for these patients, however, the limited evidence of their long‐term effects remains a matter of concern¹². If clinical trial results from Phase II are confirmed, MPC-06-ID could offer a new treatment option to patients otherwise considered unresponsive to conservative therapy, which can provide relief for at least 3 years and aims to retain the natural function and anatomy of the disc. MPCs offer the possibility to support and promote the existing regenerative potential inherent in host tissues and are expected to deliver superior long term outcomes compared to purely symptomatic treatments¹³.

 

About Grünenthal

Grünenthal is a global leader in pain management and related diseases. As a science-based, privately-owned pharmaceutical company, we have a long track record of bringing innovative treatments and state-of-the-art technologies to patients worldwide. Our purpose is to change lives for the better – and innovation is our passion. We are focusing all of our activities and efforts on working towards our vision of a world free of pain. Grünenthal is headquartered in Aachen, Germany, and has affiliates in 30 countries across Europe, Latin America and the US. Our products are available in more than 100 countries. In 2018 Grünenthal employed around 4,900 people and achieved sales of € 1.3 bn.

More information: www.grunenthal.com

Follow us on:

LinkedIn: Grunenthal Group

Twitter: @grunenthalgroup

Instagram: @grunenthal

 

About Mesoblast

Mesoblast Limited (ASX: MSB; Nasdaq: MESO) is a world leader in developing allogeneic (off-the-shelf) cellular medicines. The Company has leveraged its proprietary technology platform to establish a broad portfolio of late-stage product candidates with three product candidates in Phase III trials – acute graft versus host disease, chronic heart failure and chronic low back pain due to degenerative disc disease. Through a proprietary process, Mesoblast selects rare mesenchymal lineage precursor and stem cells from the bone marrow of healthy adults and creates master cell banks, which can be industrially expanded to produce thousands of doses from each donor without the need for tissue matching. Mesoblast has facilities in Melbourne, New York, Singapore and Texas and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). www.mesoblast.com

Follow us on:

LinkedIn: Mesoblast Limited

 

 

 

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Twitter: @Mesoblast

 

Forward-Looking Statements by Mesoblast

This announcement includes forward-looking statements that relate to future events or Mesoblast’s future financial performance and involve known and unknown risks, uncertainties and other factors that may cause Mesoblast’s actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward- looking statements. Mesoblast makes such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. Forward-looking statements include, but are not limited to, statements about the timing, progress and results of Mesoblast’s preclinical and clinical studies in CLBP; Mesoblast and its collaborators’ ability to advance product candidates into, enroll and successfully complete, clinical studies; the timing or likelihood of regulatory filings and approvals for CLBP; and the pricing and reimbursement of Mesoblast and its collaborators’ product candidates, if approved. You should read this press release together with Mesoblast’s risk factors, in Mesoblast’s most recently filed reports with the SEC or on Mesoblast’s website. Uncertainties and risks that may cause Mesoblast’s actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. Mesoblast does not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.

 

 

For further information, please contact:

 

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Nasdaq: MESO ASX: MSB Chronic Low Back Pain: MPC-06-ID Strategic Development & Commercialization Partnership with Grünenthal for Europe & Latin America 10 September 2019 Exhibit 99.2

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS This presentation includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. All statements other than statements of historical facts contained in this presentation are forward-looking statements. Words such as, but not limited to, “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “targets,” “likely,” “will,” “would,” “could,” and similar expressions or phrases identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and future events , recent changes in regulatory laws, and financial trends that we believe may affect our financial condition, results of operation, business strategy and financial needs. These statements may relate to, but are not limited to: expectations regarding the safety or efficacy of, or potential applications for, Mesoblast's adult stem cell technologies; expectations regarding the strength of Mesoblast's intellectual property, the timeline for Mesoblast's regulatory approval process, and the scalability and efficiency of manufacturing processes; expectations about Mesoblast's ability to grow its business and statements regarding its relationships with current and potential future business partners and future benefits of those relationships; statements concerning Mesoblast's share price or potential market capitalization; and statements concerning Mesoblast's capital requirements and ability to raise future capital, among others. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. You should read this presentation together with our financial statements and the notes related thereto, as well as the risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblast's actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, include, without limitation: risks inherent in the development and commercialization of potential products; uncertainty of clinical trial results or regulatory approvals or clearances; government regulation; the need for future capital; dependence upon collaborators; and protection of our intellectual property rights, among others. Accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise. | 2

Our Mission | 3 Mesoblast is committed to bringing to market innovative cellular medicines to treat serious and life-threatening illnesses

2004: Mesoblast founded in Melbourne, Australia and listed on the ASX 2014: Granted manufacturing pioneer status by Economic Development Board of Singapore 2013: Acquired MSC business from Osiris Therapeutics with trailing earn-out and milestone payments 2011: Entered into manufacturing partnership with Lonza Group in Singapore for MPC medicines 2015: Dual listed on the Nasdaq 2016: TEMCELL® HS Inj (MSC medicine) launched in Japan by Mesoblast licensee JCR 2017: Entered licensing agreement with Takeda for the treatment of certain fistulae; in 2018 Alofisel® received approval in EU 2018: Entered into partnership agreement with Tasly for cardiovascular assets in China 2019: Initiated first BLA submission to US FDA: remestemcel-L (MSC) for steroid refractory acute graft versus host disease (aGVHD) Corporate History 2010: Entered into strategic alliance with Cephalon to develop and commercialize MPC therapeutics 2019: Smith & Nephew acquired Osiris Therapeutics, became Mesoblast’s licensor for the MSC business Over a decade of scientific, manufacturing, clinical development and corporate development experience targeted at bringing to market allogeneic, off-the-shelf cellular medicines for inflammatory diseases | 4 2019: Strategic Partnership in Chronic Low Back Pain in Europe & Latin America with Grünenthal

| 5 Premier Global Cellular Medicines Company Commercialization Innovative Technology Platform1 Innovative technology targets some of the most severe disease states refractory to conventional therapies Well characterized multimodal mechanisms of action Underpinned by extensive, global IP estate Mesenchymal precursor cells (MPCs) and their culture-expanded progeny mesenchymal stem cells (MSCs). Licensee JCR Pharmaceuticals Co., Ltd. received the first full PMDA approval for an allogeneic cellular medicine in Japan and markets this product under its trademark, TEMCELL® Hs Inj. Licensee Takeda received first central marketing authorization approval from the European Commission for an allogeneic stem cell therapy and markets this product under its trademark Alofisel®. Late Stage Pipeline Initiated rolling filing with US FDA for approval for steroid-refractory aGVHD Two Phase 3 product candidates – heart failure and back pain – with near term US trial readouts Heart failure Phase 3 product candidate partnered in China Building US sales force for aGVHD launch, if approved Industrial-scale manufacturing to meet commercial demand First approved products commercialized by licensees in Japan2 and Europe3 Continued growth in royalty revenues from strategic partnerships

Commercial Scale Manufacturing Capability Scalable allogeneic “off-the-shelf” cellular medicine platform Manufacturing meets stringent criteria set by international regulatory agencies including FDA and EMA Robust quality assurance processes ensure final product with batch-to-batch consistency and reproducibility Culture expansion scalable for near term commercial needs Proprietary xeno-free technologies being developed to enable sufficient yields for long term global commercial supply Next generation processes using 3D bioreactors to reduce labor and drive down cost of goods Lonza contract manufacturing facility in Singapore | 6

Markets U.S., Europe, China, and Japan Diseases All Tier 1 & Tier 2 Indications, and multiple additional conditions Sources Allogeneic, Autologous, (Bone Marrow, Adipose, Dental Pulp, Placenta), Pluripotent (iPS) ~995 patents and patent applications (68 patent families) across all major jurisdictions Covers composition of matter, manufacturing, and therapeutic applications of mesenchymal lineage cells Enables licensing to third parties for different indications, when in alignment with our corporate strategy e.g.TiGenix (subsequently acquired by Takeda) Provides strong global protection against competitors seeking to develop products in areas of core commercial focus Mesenchymal Lineage Precursors and Progeny Global IP Estate Provides Substantial Competitive Advantage |

IN DEVELOPMENT PLATFORM PRODUCT THERAPEUTIC AREA APPROVAL COMMERCIAL RIGHTS MSC (Bone Marrow) TEMCELL® HS Inj1 Acute Graft Versus Host Disease Japan MSC (Adipose) Alofisel®2 Perianal Fistula Global MARKETED Commercial and Late-Stage Product Pipeline This chart is figurative and does not purport to show individual trial progress within a clinical program PLATFORM PRODUCT CANDIDATE THERAPEUTIC AREA PRE-CLINICAL PHASE 2 PHASE 3 COMMERCIAL RIGHTS MSC suite Remestemcel-L Acute Graft Versus Host Disease Crohn’s Disease Knee Osteoarthritis Revascor Advanced HF (Class II/III) End-Stage HF (Class III/IV) China ROW MPC suite MPC-06-ID Chronic Low Back Pain Europe Lat Am ROW MPC-300-IV Rheumatoid Arthritis Diabetic Nephropathy 1st allogeneic regen med approved in Japan 1st allogeneic regen med approved in Europe BLA submission to FDA underway TEMCELL® Hs. Inj. is a registered Trademark of JCR Pharmaceuticals Co Ltd Alofisel® is a registered Trademark of Takeda Pharmaceuticals

Key Terms of the Strategic Partnership with Grünenthal GmbH Grünenthal takes exclusive license to develop and commercialise MPC-06-ID Indication: for discogenic chronic back pain, disc degeneration and/or functional disability Territory: Europe and Latin America/Caribbean In consideration, Mesoblast will receive Up to US$150 million in upfront and milestone payments prior to product launch, as well as further commercialisation milestone payments. Payments include commitments up to US$45 million within the first year comprising US$15 million on signing, US$20 million on receiving regulatory approval to begin a confirmatory Phase III trial in Europe, and US$10 million on certain clinical and manufacturing outcomes Cumulative milestone payments could exceed US$1 billion depending on the final outcome of Phase III studies and patient adoption.   Mesoblast will also receive tiered double digit royalties on product sales. Mesoblast retains the rights for the rest of world, including the US and Japan markets | 9

Transaction Benefits to Mesoblast Strong commercial partner Delivers commercialization, distribution, sales & marketing Field force comprises around 1,600 people across Europe, Latin America & US – overall focus is on pain – visited nearly 300,000 stakeholders in 2018 (physicians, pharmacists & health administrators) Provides knowledge and knowhow in manufacturing, regulatory affairs (Europe in particular) Advances approval pathway Provides funding for Phase 3 trial in Europe reducing Mesoblast cash outflow Mesoblast and Grünenthal will collaborate on the study design for a confirmatory Phase 3 trial in Europe Confirmatory European and US (currently ongoing) Phase 3 trials are expected to support regulatory approval in both Europe and US ü Transaction focuses on Europe Mesoblast maintains rights to all other geographic markets, including US, Japan and China for additional partnering opportunities to maximize shareholder return Third party endorsement provides validation of technology platform |

Grünenthal – Global Leader in Pain Management Overview Grünenthal is a global leader in pain management and related diseases, with 50 years in pain research A long track record of bringing innovative treatments and state-of-the-art technologies to patients worldwide Strong and capable team with c. 4,900 employees worldwide Solid revenue base with € 1.3 billion in 2018 (c. US$1.5 billion) Commercial presence in 30 countries across Europe, Latin America and the US Products are sold in more than 100 countries #2 Europe1 Source: Grünenthal The ranking based on corporation sales (fixed EUR acc. IQVIA – Status 2018-Q4) in the area of major centrally acting analgesics. #1 Latin America1 |

MPC-06-ID for Chronic Low Back Pain due to Degenerative Disc Disease – Commercial Opportunity

| Minimal Treatment Options Market Opportunity Burden of Illness Unmet Need Back pain causes more disability than any other condition1 Inflicts substantial direct and indirect costs on the healthcare system1, including excessive use of opioids in this patient population Minimal treatment options for patients with chronic low back pain (CLBP) who fail conservative therapy include opioids and surgery 50% of opioid prescriptions are for CLBP Over 7m patients are estimated to suffer from CLBP due to degenerative disc disease (DDD) in each of the U.S. and E.U.5 3,4,5 MPC-06-ID development program targets over 3.2m patients in U.S. and 4m in E.U.5 with moderate to severe disease Williams, J., NG, Nawi, Pelzter, K. (2015) Risk factors and disability associated with low back pain in older adults in low-and middle-income countries. Results from the WHO Study on global ageing and adult health (SAGE). PloS One. 2015; 10(6): e0127880., 2. Simon, J., McAuliffe, M., Shamim, F. (2015) Discogenic Low Back Pain. Phys Med Rehabil Clin N Am 25 (2014) 305–317., 3.Decision Resources: Chronic Pain December 2015., 4. LEK & NCI opinion leader interviews, and secondary analysis., 5. Navigant: Commercial Assessment for a Proprietary Cell-Based Therapy for DDD in the U.S. and the EU3 – August 2014., 6. HealthCare Utilization and Cost of Discogenic Lower Back Pain in the US – Anthem/HealthCore. Disease modifying therapy for durable improvement in pain and function has potential to prevent progression to opioid use or surgical intervention MPC-06-ID: A New Paradigm for Treatment of Chronic Low Back Pain Due to Degenerative Disc Disease

Approx. 10 – 15% of Adult Population Suffers from Chronic Lower Back Pain Across the 7 Major Pharmaceutical Markets US prevalence 33.4 million, EU5 39.4 million, Japan 14.9 million Growth in the prevalence of CLBP in the U.S. going forward will likely mirror the growth rate of the overall population2 CLBP is most common within the 45-64 age group CLBP is nearly twice as common in women as in men in the same age group Higher percentage of CLBP patients seeking medical care in the EU3 (~70-80%) compared to the U.S. (~55 – 60%) mainly driven by the broader healthcare coverage in the EU3 “… Most of the patients with CLBP will see a doctor, because medical care is free in Germany …” Orthopedist, Private practice, Prevalence of Chronic Lower Back Pain (millions)1 1 Decision Resources: Chronic Pain Report 2015 2 LEK Primary / Secondary Research 2013 |

| Primary Care Physician (50%) Other (Ortho-/Spine Surgeon, Neurosurgeon, Rehabilitative Medicine Specialist, and Interventional Radiologist) (10%) Patient Presents With Symptoms Pain Specialist or Anesthesiologist (40%) Physical exam Pain scales Imaging (MRIs, X-rays) Imaging Facet joint blocks (nerve blocks) Discography Imaging Facet joint blocks (nerve blocks) Discography Stakeholder Diagnostic Modalities US/EU Patient Journey – 50% of Patients With Moderate-to-Severe CLBP Progress To Specialists For Diagnosis And Treatment Of Discogenic Cause Navigant:  Commercial Assessment for a Proprietary Cell-Based Therapy for DDD in the U.S. and the EU3 – August 2014.

Current Patient Treatment Journey (US/EU) for Discogenic CLBP (DCLBP): MPC-06-ID Potential First-Line for DCLBP Refractory to Conservative Treatments | Conservative treatments Products NSAIDs Physical therapy Chiropractic treatments Acupuncture Anticonvulsants (e.g., gabapentin) Opioid analgesics Interventional therapies Surgeries Weak opioid analgesics (e.g., tramadol) Strong opioid analgesics (e.g., oxycodone) Epidural steroid injections (off-label) Radio frequency ablation Spinal cord stimulation Intrathecal pumps Spinal fusion Disc replacement MPC-06-ID: targeting moderate-to-severe DCLBP

Chronic Low Back Pain Inflammation is at the Core of Degenerative Disc Disease McCann MR and Seguin CA. Notochord Cells in Intervertebral Disc Development and Degeneration. J. Dev. Biol. 2016, 4(1), 3; doi:10.3390/jdb4010003 |

MPC-06-ID IL-1β TNFα M1 M2 Macrophage Polarization Inflammation IL-1, IL-6 TNFα Neurite ingrowth Neuropathic pain Structural integrity of annulus Proteoglycans in nucleus MPC-06-ID: Potential Mechanisms of Action in Treating Inflammatory Disc Disease

Control Treatment being used in the Phase 3 Program MPC Dose being used in the Phase 3 Program Phase 2 Clinical Trial – Randomized Patient Allocation Patients with Moderate DDD Randomize Control Treatments (n=40) MPC Treatments (n=60) Saline (n=20) Hyaluronic Acid (n=20) 6M MPCs (n=30) 18M MPCs (n=30)

Phase 2 Clinical Trial Clinical Study Patient Population A prospective, multicenter, double blinded, controlled clinical study comparing two doses of immunoselected, culture-expanded, nucleated, allogeneic MPCs when combined with hyaluronic acid to two control intradiscal injections in subjects with chronic low back pain (> 6 months) due to moderate DDD at one lumbar level from L1 to S1 and unresponsive to conservative therapy for at least 3 months (including physical therapy) Inclusion Criteria DDD with back pain >6 months Failed 3 Months Non-Operative Care Patients with a modified Pfirrmann score of 3, 4, 5 or 6 With or without contained disc herniation up to a 3mm protrusion with no radiographic evidence of neurological compression Disc height loss of <30% compared to a normal adjacent disc based upon radiographic evaluation VAS Back pain >40 ODI Score >30 Exclusion Criteria Modified Pfirrmann score of 1 & 2 or 7 & 8 Clinically significant nerve or sacroiliac joint pain Clinically significant facet pain as determined by a diagnostic medial branch block or facet joint injection Symptomatic involvement of more than one lumbar disc level Discs with full thickness tears with free-flowing contrast through the annulus fibrosis Lumbar intervertebral foraminal stenosis at the affected level(s) resulting in clinically significant spinal nerve root compression

Phase 3 Responder Criteria Used in Post-Hoc Assessment of Phase 2 Clinical Trial Results Questionnaire Scoring Range MIC (Absolute Cutoff) MIC (% Improvement from Baseline) MSB Phase 3 Cutoff Visual Analog Scale (VAS) 0-100 15 points 30% 50% Oswestry Disability Index (ODI) 0-100 10 points 30% 15 points Mesoblast Phase 3 VAS and ODI Cutoffs 50% VAS reduction based upon KOL, regulatory, and payer input 15 point ODI reduction based upon previous FDA approvals of spine products, such as artificial disc replacements and spine fusion devices FDA Guidance on Minimally Important Change (MIC) for Pain and Function1 using a composite endpoint consistent with the CDRH IDE guidance for spinal systems (i.e. spine fusion & artificial disc replacement 1. Ostelo et al. (Spine Vol 33,no1.pp90-94) established MICs for the most frequently used questionnaires to evaluate pain and function in patients with chronic low back pain

B: Phase 2: Treatment Success Responders1,2 at both 12 & 24 Months p = 0.050 Subjects with missing data are classified as non-responders. Treatment Success Responders have a 50% reduction in LBP as measured by VAS AND a 15 point improvement in function as measured by ODI at a) 12 months, and b) both 12 and 24 months and no intervention through 24 months. A: Phase 2: Treatment Success Responders1,2 at 12 Months p = 0.032 Chronic Low Back Pain MPC-06-ID – Post-Hoc Phase 2 results provide target endpoints for Phase 3 trial |

Phase 2 Clinical Trial – 36 Month Results MPC therapy provides durable results through 36 months Over 36 months: 82% of the 6 million MPC group who achieved the Phase 3 primary endpoint composite over 24 months maintained treatment success1 86% of the 6 million MPC group who successfully met the Phase 3 pain responder criteria (50% pain reduction with no additional intervention at both 12 and 24 months) remained pain responders2 92% of the 6 million MPC group who met the Phase 3 functional responder criteria (15-point reduction in ODI and no additional intervention at both 12 and 24 months) remained functional responders3 There were no significant differences in safety events cell-treated patients and controls over 36 months Composite Responder must have an optimal pain (50% reduction in VAS) AND function (15 point reduction in ODI) response AND no additional intervention. Pain Responder must have an optimal pain response (50% reduction in VAS) AND no additional intervention. Functional Responder must have an optimal functional improvement (15 point reduction in ODI) AND no additional intervention.

MPC-06-ID – Ongoing US Phase 3 Clinical Trial Three-arm study comparing 6-million MPC with or without hyaluronic acid (HA) against saline control Primary efficacy endpoint agreed to with FDA: Overall Treatment Success Composite at both 12 and 24 months as measured by: At least 50% reduction from baseline in Visual Analogue Scale (VAS) pain score at both 12 and 24 months post-treatment; and At least a 15 point decrease from baseline in Oswestry Disability Index (ODI) function score at both 12 and 24 months post-treatment; and No interventions affecting the treated disc through 24 months Study powered to show efficacy for both 6-million MPC arms (with and without HA) 404 patient 2:1 randomized Phase 3 trial completed enrollment March 2018; all patients have completed 12 month safety and efficacy follow-up |

MPC-06-ID – Development Strategy for US & Europe Phase 3 trial in chronic low back pain completed enrollment in March 2018 with 404 patients randomized to receive MPC-06-ID or placebo. All patients have now completed at least 12 months of safety and efficacy follow-up. Follow-up continuing to a 24-month assessment of safety and efficacy by the first quarter of CY 2020, with readouts planned mid-CY2020 Initiate confirmatory Phase 3 trial in Europe in partnership with Grünenthal Complete commercial manufacturing in partnership with Grünenthal Results of confirmatory Phase 3 clinical trials in US and Europe, together with commercial manufacturing, expected to support regulatory approval and commercial launches in both Europe and US for MPC-06-ID in chronic discogenic low back pain |