APPENDIX B – CIRM TRANSLATIONAL PORTFOLIO CANCER: HEMATOLOGIC MALIGNANCY DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY Existing candidate molecules (3 small molecule, 3 mAbs) targeting leukemic stem cells (LSC) by blocking survival and self-renewal DR1-01430 Disease Team I IND AML, CML, ALL, CLL pathways that function preferentially in human LSC compared to normal HSC Monoclonal antibody against CD47 – “Don’t eat me” antigen that is DR1-01485 Disease Team I IND AML expressed on leukemia stem cells and inhibits their phagocytosis by macrophages Early TR2-01789 DC CML Small molecule pan BCL-2 inhibitor targeting cancer stem cells Translation II Early TR2-01816 DC AML, ALL Small molecule inhibitor of BCL6 targeting cancer stem cells Translation II

CANCER: SOLID TUMORS

DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY

Colon, ovarian Small molecules specific for each of two drug targets in cancer stem DR1-01477 Disease Team I IND cancers, glioblastoma cells

Allogeneic hNSC line to target tumor, engineered ex vivo to deliver DR1-01421 Disease Team I IND Glioblastoma carboxylesterase to locally convert CPT-11 to more potent SN-38

Allogeneic hNSC, either of two lines, or hMSC to target tumor, DR1-01426 Disease Team I IND Glioblastoma engineered ex vivo to deliver a tumorcidal gene product, TRAIL or cytosine deaminase, and a suicide gene

Early Tumor homing by hMSC genetically engineered to produce TR2-01791 DC Glioblastoma Translation II replication competent retrovirus encoding a suicide gene

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NEUROLOGIC DISORDERS: INJURY DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY Targeted Spinal Cord Injury CT1-05168 Clinical Ph I hESC-derived oligodendrocyte progenitor cells (thoracic, cervical) Development Spinal Cord Injury Early TR2-01785 DCF (conus medullaris, hESC-derived motor and autonomic precursor neurons Translation II cauda equina) Early TR2-01767 DCF Traumatic brain Injury Allogeneic hESC-derived NSC Translation II Allogeneic hESC-derived NSC line alone or in combination with DR1-01480 Disease Team I IND Stroke matrix

NEUROLOGIC DISORDERS: NEURODEGENERATIVE DISEASE

DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY Disease Allogeneic hESC-derived astrocyte precursors delivered into spinal cord DR1-01471 IND ALS Team I (delivery device) Allogeneic hESC-derived NSC or hESC-derived NSC genetically Early TR1-01245 DC Alzheimer's Disease modified with a beta-amyloid degrading enzyme or a transcription factor Translation I that promotes neuronal differentiation for transplantation Early Allogeneic hMSC engineered ex vivo to express siRNA targeting mutant TR1-01257 DC Huntington's Disease Translation I huntingtin mRNA. Injected intracranially Early Allogeneic hESC-derived neural stem or progenitor cells for TR2-01841 DC Huntington's Disease Translation II transplantation Early The best of either hNSC derived from tissue, ESC, or iPSC or hVM TR1-01267 DC Parkinson's Disease Translation I (ventral mesencephalon) precursors derived from ESC, NSC or tissue Early TR2-01856 DC Parkinson's Disease Allogeneic hPSC-derived dopaminergic neurons Translation II Early Small molecule modulator of neuroinflammation identified by screening TR2-01778 DCF Parkinson's Disease Translation II on astrocytes/microglial from patient derived iPSC 2

NEUROLOGICDISORDERS: NEURODEGENERATIVE DISEASE, PEDIATRIC

DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY

Early Autologous iPSC-derived neural or oligodendrocyte progenitors, TR2-01832 DCF Canavan Disease Translation II genetically modified to correct mutant aspartoacylase (ASPA) gene

Early Small molecule that increases SMN1 gene product in patient iPSC- TR2-01844 DC Spinal Muscular Atrophy Translation II derived motor neurons NEUROLOGIC DISORDERS DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY Neurons from ASD (and control) iPSC for phenotype screening, Early Autism Spectrum Disorder TR2-01814 DCF assay development and validation, drug screening and biomarker Translation II (ASD) identification Early hESC-derived progenitors of GABAergic inhibitory neurons TR2-01749 DCF Refractory epilepsy Translation II analogous to those in medial ganglionic eminence

EYE DISEASE DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY Disease Age-related macular Allogeneic functionally polarized hESC-derived RPE monolayers on DR1-01444 IND Team I degeneration (dry form) synthetic substrate implanted sub-retinally

Early Age-related macular TR1-01219 DC Autologous iPSC-derived RPE (generated without integrating vectors) Translation I degeneration (dry form)

Early Age-related macular Autologous adult SC (CMZ) or iPSC-derived RPE +/- ex vivo TR1-01272 DC Translation I degeneration (dry form) engineering to express negative regulators of complement cascade Early TR2-01794 DC Retinitis Pigmentosa Allogeneic retinal progenitor cells Translation II Early Ex vivo expansion of corneal epithelial stem/progenitor cells, also TR2-01768 DCF Corneal Injury Translation II known as limbal stem cells 3

HIV/AIDS

DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY Autologous HSC transduced ex vivo with a lentiviral vector Disease DR1-01431 IND AIDS Lymphoma engineered to express an shRNA against CCR5 & a fusion inhibitor. Team I IV administration after myeloablation Autologous HSC transduced ex vivo with non-integrating vector Disease DR1-01490 IND AIDS Lymphoma engineered to express a zinc finger nuclease targeting CCR5. IV Team I administration after myeloablation Early Autologous HSC genetically modified with multiple anti-HIV TR2-01771 DC AIDS Lymphoma Translation II resistance genes and a drug resistance gene

DIABETES & COMPLICATIONS

DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY

Allogeneic hESC-derived pancreatic cell progenitors in a device Disease DR1-01423 IND Diabetes: Type 1 implanted subcutaneously that matures in vivo to beta cells that Team I secrete insulin in response to glucose. Transient immunosuppression

Early Chronic Diabetic foot TR2-01787 DC Allogeneic hMSC on a dermal regeneration scaffold Translation II ulcers

BLOOD DISORDERS

DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY Autologous HSC, genetically corrected ex vivo by lentiviral vector Disease DR1-01452 IND Sickle Cell Disease mediated addition of a hemoglobin gene that blocks sickling. IV Team I administration after myeloablation

Early Autologous iPSC-derived HSC genetically corrected by homologous TR1-01273 DC Fanconi Anemia, XSCID Translation I recombination 4

BONE DISORDERS

DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY

Early Autologous adult perivascular stem cells and an osteoinductive TR2-01821 DC Spinal fusion Translation II protein on a FDA-approved acellular scaffold

Osteoporosis-related Early TR2-01780 DCF vertebral compression MSC in combination with PTH (parathyroid hormone) Translation II fractures

CARTILAGE DISORDERS

DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY

Early Focal cartilage defect, iPSC- or ESC-derived chondrocyte progenitors implanted into TR1-01216 DC Translation I osteoarthritis chondral defect or injected into OA joint

Early Optimized small molecule of lead molecule PRO1 that induces TR2-01829 DC Osteoarthritis Translation II chondrocyte differentiation of resident hMSC

OTHER DISORDERS

DISEASE/ AWARD # PROGRAM GOAL* APPROACH INJURY

Disease Heart Disease: Advanced Autologous cardiac derived cells, 'cardiospheres', expanded and DR1-01461 IND Team I ischemic cardiomyopathy delivered by direct catheter injection into heart muscle

Disease Skin Disease: Epidermal sheets from expanded autologous genetically corrected DR1-01454 IND Team I Epidermolysis bullosa (to express wild type COL7A1) iPSC-derived keratinocytes

Multiple: Bone fractures, Early Recombinant Wnt in a sustained release formulation to stimulate TR1-01249 DC wound healing, heart Translation I endogenous stem cells to repair tissue disease, stroke 5

Liver Disease (acute liver Early failure and as a bridge TR2-01857 DC Allogeneic genetically modified hESC-derived hepatocytes Translation II following large liver resections) Skeletal Muscle Disorders: Early Autologous skeletal muscle precursor cells derived from human TR2-01756 DCF Duchenne muscular Translation II iPSC genetically modified to correct the dystrophin gene dystrophy * The Project Goals are:

IND - file an approvable IND with the FDA DC - achieve a development candidate ready for IND-enabling preclinical development DCF - show feasibility of a potential development candidate by achieving initial proof of concept

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