Michael Werner Executive Director Alliance for Regenerative Medicine NAS Public Meeting – February 11, 2016

22 ARM’s Role in the Sector As the leading global advocate for the regenerative medicine and advanced therapies sector, ARM enables acceleration of research, development, investment and commercialization of transformational treatments and cures for patients worldwide. Drives regulatory, scientific and policy advancement Maximizes market access and reimbursement Enables sustainable access to capital

3 3 Promise & Potential of Genome Editing in Somatic Cells Genome editing technologies (including zinc finger nucleases, CRISPR/Cas9 and TALEN-based methods) represent a powerful new approach for targeting and changing DNA sequences in somatic (non-reproductive) human cells These technologies hold significant promise to durably treat and potentially cure devastating diseases and conditions, several with currently high degrees of unmet medical needs. Such diseases include several forms of cancer; HIV/AIDS; ocular disorders; hemoglobinopathies and other blood disorders; neurodegenerative disorders; and various rare or orphan diseases, such as Duchenne muscular dystrophy, sickle cell disease, lysosomal storage disorders and many more. The patient population could number in the hundreds of thousands, possibly millions, worldwide

4 ARM’s Position on Human Germline Editing ARM encourages and promotes the use of genome editing technologies in somatic (non- reproductive) human cells to durably treat and potentially cure devastating human diseases and conditions. In our Nature commentary piece, published March 2015, ARM called for a temporary moratorium on research involving the using of genome editing technologies and their use on human germline cells. Following the December 2015 NAS summit on Human Gene Editing, ARM stated that until the many unresolved safety, ethical and legal concerns surrounding the use of gene editing techniques to manipulate or modify the human germline are adequately addressed, our position is that pursuing this line of research is not appropriate at this time.

Potential Commercial Landscape Somatic cell genome editing therapeutic products offer many potential commercial opportunities. Given the sizeable patient community and the unparalleled therapeutic benefits these technologies stand to offer, analysts estimate the global genome editing market could surpass $3.5B (USD) by the end of this decade. 1 CRISPR and other genome-editing technologies also offer the promise of replacing less efficient and costlier procedures, making drug discovery more targeted and addressing the root cause of disease, rather than managing the symptoms, offering significant additional economic benefits for the healthcare system. Given the promising scientific breakthroughs gene editing technologies represent, this field’s complex IP landscape continues to evolve, the results of which will have significant impact on the field and future commercial landscape. 1 “Genome Editing / Genome Engineering Market by Application (Cell Line Engineering, Animal & Plant Genetic Engineering), Technology (CRISPR, Antisense, TALEN, Zinc Finger Nuclease), & End User (Biotechnology & Pharmaceutical, CRO) - Global Forecast to 2019”, marketsandmarkets – April 2015

Present Commercial Landscape The present commercial landscape for genome editing includes a number of different types of companies: product developers, tools and reagent providers, pharmaceutical companies, contract research organizations and more. This includes the following: Abeona Therapeutics Addgene Advanced Analytical Technologies American Type Culture Collection AstraZeneca Batu Biologics Bayer Healthcare Biocytogen Biogen BIO-RAD Laboratories bluebird bio Bristol Myers-Squibb Caribou Biosciences Cellecta Celgene Cellectis Cibus CRISPR Therapeutics Cyagen Dharmacon Dow Editas Medicine GlaxoSmithKline (GSK) Genecopoeia GE Healthcare GenScript Herabiolabs Horizon Discovery Intellia Therapeutics Integrated DNA Technologies Juno Therapeutics Merck MirusBio Novartis Orig3n Pfizer Poseida Therapeutics Recombinetics Sangamo BioSciences Shire SigmaAldrich ThermoFisher Transpogen Twist Bioscience Vertex Pharmaceuticals Please note: this is not an exhaustive list of all the companies active in genome editing 6

bluebird bio Therapeutic Developer Case Studies Type of genome editing technology: bluebird bio employs megaTALs / homing endonuclease-based technology for generating precise genetic alterations to target cells. Stage of development: bluebird’s genome editing technology is currently in pre-clinical development and is being investigated across a range of potential applications (including T cells for oncology). The first publicly announced application of bluebird’s genome editing technology is in collaboration with Kite Pharma in the context of a HPV-specific TCR-based T cell immunotherapy. Disease focus areas: T cells for oncology and other yet-undisclosed applications 7

Therapeutic Developer Case Studies Sangamo BioSciences Type of genome editing technology: Proprietary technology based on the engineering of a naturally occurring class of DNA-binding zinc-finger proteins (ZFPs). Stage of development: Phase 2 clinical program to evaluate the safety and efficacy of novel ZFP Therapeutics for the treatment of HIV/AIDS (SB-728) Phase 1/2 clinical program to evaluate safety and efficacy of its IVPRP approach for hemophilia B. FDA cleared Sangamo’s IND application for its Hurler syndrome (MPS I) program at the end of 2015, with the goal of initiating a Phase 1/2 clinical trial in the first half of 2016 (IND applications cleared Feb 2016) Goal to file six more IND applications to move its other preclinical programs into the clinic by the end of 2016, including IND applications for Hunter syndrome (MPS II) and beta-thalassemia (in collaboration with Biogen) in the first half of the year, and IND applications for its programs in hemophilia A, Gaucher, Fabry and sickle cell disease (Biogen), in the second half of Disease focus areas: Using its proprietary IVPRP, Sangamo is currently developing one-time, life-long therapies for blood and lysosomal storage disorders, including hemophilia A and B; Hurler syndrome (MPS I); Hunter syndrome (MPS II); Gaucher disease; Fabry disease. Sangamo is implementing its ex-vivo ZFN-mediated genome editing strategy to develop one-time treatments for hemoglobinopathies and infectious diseases, including beta-thalassemia; sickle cell disease; HIV/AIDS. 8

9 9 Supporting Genome Editing’s Therapeutic Potential The potential of somatic cell genome editing for research and therapeutic product development purposes is extremely promising and progressing rapidly These products fit within the overall existing regulatory framework: -No need for a unique oversight process -Gene editing products must undergo the same level of regulatory review as other biotech products, as appropriate -NIH-RAC – public discussion of novel technologies -ARM has several proposals designed to streamline the regulatory review process It is ARM’s goal to ensure there is no legislative or regulatory action taken that would hinder or delay the therapeutic use of these techniques