Cord Blood Market Trends, circa 2014

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GENReports: Market & Tech Analysis Cord Blood Market Trends, circa 2014 > Enal Razvi, Ph.D. Managing Director Select Biosciences, Inc. enal@selectbio.us

Topic Introduction and Scope The focus of this GEN Market & Tech Analysis Report is to provide an update on the cord blood marketplace We present here the following metrics: Growth of Cord Blood Units in the Public Banks QuanGGes of Cells Required for Cord Blood Transplants in Pediatric vs. Adult PopulaGons EvoluGon of Cord Blood TransplantaGon and Challenges Taken together, these data frame the current quanetaeve metrics and provide a snapshot of the cord blood space, circa 2014

700,000 Growth of Stored Cord Blood Units in the Public Banks Worldwide Data Current as of June 2014 600,000 Number of Stored Cord Blood Units 500,000 400,000 300,000 200,000 100,000 - Source: Bone Marrow Donors Worldwide.

Different Types/Number of Hematological Progenitors Needed for Different Types of Hematological Malignancies For Pediatric PopulaEons with Sickle- Cell Anemia Using Cord Blood Pre- cryopreservagon total nucleated cell dose of 6.4 10 7 per kg body weight (range: 3.1-7.6 x 10 7 cells per kg body weight) 1-10% of the cells infused are progenitors Post- thaw infused CD34 + cell dose of 1.5 10 5 per kg body weight (range: 0.2-2.3) 10% of the cells are progenitors For Adult PaEents with Chronic Myeloid Leukemia (CML) Using Cord Blood The median number of nucleated cells infused is 1.7 x 10 7 per kg body weight (range: 1.2 to 4.9 x 10 7 cells per kg body weight) 1-10% of cells are progenitors Different Cell Numbers and Routes GENReports: of Delivery Market Being & Tech Analysis, UElized Produced Across by Enal the Razvi, Landscape Ph.D. 2014 For Cellular Therapy using Cord Blood as the TherapeuEc Agent

Banked Cord Blood TNC Evolution What Does the Transplant Physician Want? An average TNC of 1.8 x 10 9 What Does the Typical Transplant Physician Find Today? 2.8 1.6 2.1 Source: Dr. Brian Freed, Professor of Medicine GENReports: and Immunology Market & Tech Analysis, Produced by Enal Razvi, Ph.D. 2014 University of Colorado ExecuGve Director, ClinImmune Labs HLA-A, B and DRB1 Match

Beyond Cell Dose: Selection of the Optimal Cord Blood Unit for Transplant Cell dose [the TNC count] is an important factor for ensuring engrazment success The nucleated cell dose > 3.7 x 10 7 per Kg of body weight is the most important factor for neutrophil engrazment The average TNC of a banked unit of 1.2 x 10 9 is not sufficient for an adult transplant Size of US adults is 10 Kg higher than that of the Europeans, and 15 Kg higher than that of the Asians therefore higher TNCs required in the US There is a higher incidence of GVHD and Prolonged Platelet Recovery with HLA class I and II mismatches HLA match is most important when cell dose is low Survival is best with 6/6 matched cord blood unit in pediatric recipients Generally: 1 mismatch with 2.5-5.0 x 10 7 nucleated cells/kg body weight = 2 mismatches with > 5.0 x 10 7 nucleated cells/kg body weight Low CD34 cell viability! Predictor for Poor EngraZment Infused [post- thaw] CFUs correlate best with neutrophil and platelet engrazment Pediatric Cell Dose: > 3 x 10 7 NCs/kg body weight, >5 x 10 7 NCs/kg for non- malignant disease Adult Cell Dose: 2 cords mixed together > 3 x 10 7 NCs/kg body weight IntraBone Cord Blood Transplant Cell Dose > 1.5 x 10 7 NCs/kg body weight [need 5/6 HLA match rather than a 4/6 HLA match]

Comparison of the Main Features of Cord Blood Transplants vis-à-vis Bone Marrow Transplants, Updated June 2014 Characteristic Cord Blood Transplantation Bone Marrow/Peripheral Blood Transplantation Number of Available Donors Worldwide (as of June 2014) in Public Registries 610,000 Units Stored and Available 23.58 Million Donors in the Registries Major Limiting Factor Fixed Unit Cell Count HLA Match and Donor Attrition Minimum Total Number of Nucleated Cells (TNCs) Needed for Transplantation ~2.5 x 10 7 per Kg of body weight [Generally 1.8 x 10 9 total TNCs needed] ~2.0 x 10 8 per Kg of body weight Second Graft Impossible Possible Median Speed of Donor Availability ~1 day ~3-4 months Donor Morbidity None Fatigue/Pain EBV/CMV Transmission to Recipient Risk of Transmission of Congenital Disease Negligible Possible Possible None Standard HLA Match Requirements Minimum GENReports: 4 out of 6 Market & Tech Analysis, Mostly Produced 8 of by 8 Enal Razvi, Ph.D. 2014

Cost Metrics There has been much discussion of the cost structure underlying the cord blood transplantaeon marketplace and the challenges this poses for the sustainability of this industry Range of costs per unit of cord blood banked: US$300- US$2,000 Average cost of producgon of a unit of cord blood : US$900 Average price of cord blood units Single Cord Priced at US$39,400 Double Cord Priced at US$78,800 There is a declining number of cord blood transplants being performed in the US Some of the reason behind this trend may be the high cost of the cord blood since cord blood transplants in adult pagents require two cords as a means to hit the TNC number required Another reason may be that other procedures may offer befer clinical outcomes in terms of engragment rate However, there is increasing cord blood transplantaeon in Japan, China, UK, and France Source: Mike Boo PresentaGon at Cord Blood Conference, San Francisco, 2014

Cost Metrics, continued. Indeed the costs of cord blood transplantaeon are increasing due to the FDA requirement that cord blood banks be licensed and this regulaeon is driving cost increases The costs of producing cord blood units has increased 10-20% On the other hand, the transplant centers (the end user community) are driving down the costs of cord blood, especially for the adults where double cords are required this is pupng downward pressure on revenue generaeon to the industry Source: Joanne Kurtzberg, Duke University Industry s Business Model Needs to Adjust or be Modified

Key Takeaways: Quantitative Utilization Trends of Cord Blood and the Associated Challenge in this Space Annual Turnover (UElizaEon) of cord blood units from public banks: 1-3% of units inventoried These are serious challenge in this space Large numbers of stored cord blood units have sub- opgmal total nucleated cell (TNC) count and therefore are unsuitable for transplantagon/cellular therapy The turnover of stored cord blood is exceedingly low and this is a driver for the high costs of the stored cord blood units Compliance with US FDA regulagons/licensure of cord blood banks increases cost per unit shipped New therapeugc applicagons will be needed to drive forward the uglizagon of cord blood in cellular therapy New technologies for cell expansion need to be developed