Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Cytokinesis wikipedia , lookup
Cell growth wikipedia , lookup
Extracellular matrix wikipedia , lookup
Tissue engineering wikipedia , lookup
Cell culture wikipedia , lookup
Cellular differentiation wikipedia , lookup
List of types of proteins wikipedia , lookup
Cell encapsulation wikipedia , lookup
Organ-on-a-chip wikipedia , lookup
The Adult Stem Cell Company Building Blocks for Better Health Our Mission “Mesoblast Limited aims to become the world leader in novel therapeutic treatments for patients with bone and joint diseases. Our primary focus is the rapid and successful commercialisation of a proprietary, high-margin, adult stem cell platform for the treatment of conditions with very large, unmet global markets, including bone fractures, spinal disease, damaged joint cartilage, and intervertebral disc disease”. Stem Cells Are Human Building Blocks Stem Cells • • • building blocks for blood, bone, cartilage, fat, vasculature, heart muscle can be extracted from various sites can be used to repair and regenerate a wide range of tissues and organs Advantages Of Stem Cells Over Other Medical Therapies • • • natural biologicals, safer, less likely to have side-effects regenerate tissues, reducing long-term health care costs restore function and quality of life Adult Stem Cells: The Right Building Blocks Advantages Of Adult Stem Cells Over Embryonic Stem Cells • • • • no ethical issues surrounding embryo creation and destruction more mature, hence shorter and less costly development processes significantly reduced risk of cancer formation not recognized as foreign by immune system of an unrelated party Therefore, Adult Stem Cells Are Much Closer To Market Adult Stem Cells: Haematopoietic vs Mesenchymal Adult Tissue Contains Two Types of Stem Cells: • • haematopoietic precursor cells: frequent; blood, bone marrow precursors mesenchymal precursor cells (MPC): rare; bone, cartilage, fat, muscle, artery precursors Advantages Of Mesenchymal Precursors Over Haematopoietic Precursors: • • • if isolated, can be easily cultured and expanded can generate various tissue types needed for functional restoration not recognized as foreign by immune system of an unrelated party Proprietary MPC Isolation Bone Marrow spin adhere to dish Bone Marrow (BM) BM + stem cell-binding antibody 1 hour, on ice second binding reagent density solution 1/2 hour, on ice microbeads (Miltenyi) mixed cell culture Historical Isolation Method 1/4 hour, on ice MACS magnet Competitive Advantages: Precise identification, ease of isolation and scale-up • 1000-fold purer initial stem cell pool • homogeneous population, high rate cell division • efficient large-scale expansion • lower costs of cell culture process • greater potency of expanded, cultured product MPCs Give Rise To Various Tissue Types: Potential Therapeutic Markets! Mesenchymal Precursor Cell, MPC MPC Isolated and Cultured bone Orthopaedic cartilage other cell types Adult Stem Cell Self-Renewing Stem cell heart muscle smooth muscle Cardiac Differentiated cell arteriole Very Large, Unmet Orthopaedic Markets 1. Bone Regeneration/Fracture Repair: (a) delayed or non-union fractures (>500,000 in US annually) (b) vertebral fusion (300,000 in US annually) (c) osteoporosis-related fractures (>700,000 vertebral, femoral neck in US annually) existing therapies inadequate, use of own bone traumatic, MPC regenerate bone 2. Vertebral Disc Regeneration affects 20% of population, results in back pain and nerve impingement existing therapies inadequate, MPC produce material similar to disc cartilage 3. Cartilage Regeneration in Joints (a) chronic arthritis of knee ( >800,000 arthroscopic knee surgery in US annually) (b) acute meniscal tears existing therapies inadequate, MPC produce material similar to articular cartilage Very Large, Unmet Cardiovascular Markets 1. Acute Myocardial Infarction (AMI or Heart Attack) >1.1 million heart attacks in US annually 46% develop heart failure due to loss of heart muscle <6 years existing therapies inadequate MPC can increase blood vessels, protect and rebuild heart muscle 2. Congestive Heart Failure (CHF) affects 5 million Americans (2% of the population) 550,000 new US cases annually existing therapies modest efficacy, symptomatic relief only MPC can rebuild heart muscle, alleviating the condition 3. Peripheral Artery Disease (PAD) and Wound Healing >8 million in US suffer from PAD >400,000 angioplasties annually to prevent limb amputation >800,000 diabetic foot ulcers annually MPC likely to improve blood flow to limbs Delivering A High-Margin Business Model: An “Off-the-Shelf” Product • lack of immune activation: one “universal” donor provides MPC for multiple unrelated recipients (allogeneic), contrasting with other cell therapies (autologous) • purity of MPC starting material: one “universal” donor can provide easy scale-up, many dosages • easy access to source material: pay “universal” donors using existing FDA guidelines • centralised manufacture and distribution: commercial quantities of clinical-grade MPC product easily delivered to market as an “off the shelf” product • pharmaceutical range profit margins • proprietary MPC technology -- long term market protection Strategic Vision: Biological Therapy To Complement Existing Device Markets Orthopaedics MPC may be combined with • cements/polymers for fractures (e.g Zimmer, Smith & Nephew, Johnson & Johnson) • fracture repair devices (e.g. Kyphon) • vertebral cages for vertebral fusion (e.g. Medtronic) • other biologicals for bone/cartilage regeneration (e.g. Medtronic, Stryker) • delivery devices for percutaneous injection into vertebral disc/knee cartilage Cardiovascular MPC may be combined with • catheters for coronary/myocardial injection (e.g Johnson & Johnson, Guidant, Medtronic) • minimally invasive surgical delivery devices (e.g. Ethicon, Guidant, Medtronic) • devices/biomaterials for wound healing (e.g. Johnson & Johnson) Executing Results-Oriented Commercial Strategy • milestone-driven and outcome-focused • continuous engagement of strategic corporate partners to generate early revenues in multiple fields, geographies e.g. orthopaedic delivery companies, cardiac catheter companies, Big pharma • minimise corporate costs, whilst maximising intelligent use of outsourcing • deliver therapeutic products to increase quality of life and materially reduce health care costs Milestone-Driven, Rapid Commercialisation Clinical trial protocol Australian human trials • orthopaedic (auto) • cardiovascular (auto) Safety/toxicology GMP process FDA/IND filing (allo) • orthopaedic • cardiovascular IND approval/US trials IP development 2005 Corporate partnerships 2006 2007 FDA IND GMP Process for Allogeneic cells Clinical Studies Allogeneic Ib/IIa randomised, controlled Clinical Studies Autologous Ib open label Large Animal Studies (sheep) Allogeneic Tox/Efficacy Orthopedic bone fracture, spine fusion Orthopedic bone fracture, spine fusion Orthopedic long bone fracture, vertebral disc knee OA Cardiovascular myocardial infarct, catheter delivery Cardiovascular chronic ischemia, catheter delivery Cardiovascular acute ischemia, heart failure mAb production immunoselection serum-free culture, batch scale-up GMP process for Autologous cells immunoselection, culture, scale-up GMP facility immunoselection, batch scale-up IND Development Plan • contract development and supply agreement for GMP mAb for cell isolation • contract FDA-licensed cell culture facility in US for allogeneic batch production • contract Australian cell culture facility for autologous cell production • optimise cell culture conditions, including serum-free media • contract Australian medical centres for autologous clinical trials • contract US and other medical centres for allogeneic clinical trials • contract GMP facility for analogous mAb/cell culture conditions for sheep cells • contract animal facilities for orthopedic/cardiac sheep studies (tox/efficacy) Benefits of Autologous Human Clinical Trials • optimise ex vivo culture process • • • • • • improve cell engraftment and survival (e.g. matrix) identify appropriate clinical indications amenable to therapy determine optimal cell dose for safety/efficacy maintain careful registry of adverse events determine best route of administration early validation of technology Data valuable for inclusion in FDA dossier for IND application to initiate safety/efficacy trials with allogeneic cells Early Achievements External Validation ¸ December 2004, floated with exceptional institutional and retail investment support, share price has remained significantly above issue. ¸ Mesoblast Chief Scientific Advisor awarded $1.5 million grant from Australian National Health & Research Medical Council for mesenchymal adult stem cells. ¸ substantial early interest from a number of leading global medical device and pharmaceutical companies re possible collaborative and commercial relationships. Organisational ¸ project management, regulatory, and clinical groups established, working in concert with Angioblast team to ensure efficient execution of the Joint Expenditure Program. ¸ February 2005, Mesoblast regulatory team attended FDA advisory meeting, which served to reinforce regulatory pathway for cellular therapy in orthopedic indications. Early Achievements, C’td. Regulatory ¸ FDA-licensed manufacturing facilities have been identified for large-scale GMP production of MPC to be used in pivotal, multi-center clinical trials for FDA approval. ¸ key US orthopaedic and cardiovascular opinion leaders with extensive FDA experience in pre-clinical safety and toxicologic studies have been identified. Pilot Clinical Trials ¸ Pilot Clinical Trials will commence in Australia this year, evaluating safety and efficacy of autologous (patients’ own) MPC. Specific advances include: o o o o identification of lead orthopaedic and cardiovascular clinical indications selection of key Australian opinion leaders and hospital sites preparation of Ethics Committee Submissions well advanced contracting of Cell Therapies Pty Ltd, the cell processing facility of the Peter MacCallum Cancer Centre in Melbourne, to manufacture MPC for these trials Mesoblast has developed a communications strategy to ensure that the market is thoroughly informed in a timely basis on the progress of the Pilot Clinical Trials. Market Guidance For Second Quarter 2005 Regulatory ¸ formalise contractual arrangements with FDA-licensed manufacturing facilities for large-scale GMP production of MPC to be used in pivotal, multi-centre clinical trials for FDA marketing approval. ¸ formalise contractual arrangements with key US orthopaedic and cardiovascular opinion leaders to perform pre-clinical safety and toxicologic studies. Pilot Clinical Trials ¸ complete Ethics Committee submissions to multiple Australian hospitals for Pilot Clinical Trials evaluating safety and efficacy of autologous (patients’ own) MPC in lead orthopaedic and cardiovascular clinical indications. ¸ while timing of ethics approval, patient recruitment and enrolment will be at sole discretion of the medical centres and the clinicians involved, Mesoblast’s goal is to commence Pilot Clinical Trials in as short a timeframe as possible. . Experienced Board of Directors Chair Mesoblast: Michael Spooner - ex Ventracor MD & CEO Directors: Donal O’Dwyer - ex worldwide President Cordis (J&J) Byron McAllister - ex VP Ares-Serono (FDA expert) Prof. Silviu Itescu - Columbia (USA) and Melb. Uni., Corp & FDA advisor Chair Angioblast: Carter Eckert - ex CEO Knoll, ex Pres Baxter Pharmaceuticals Chair SAB: Prof. Silviu Itescu Members: Prof. Stephen Graves - Director Orthopaedic Research, Royal Melbourne Prof. Robert Graham - Exec. Director Victor Chang Institute, Sydney Prof. Henry Krum - Pfizer Global Advisory Board Prof. Richard Gilbert - Consultant Lilly&Co., Merck, GlaxoSmithKline