The state stem cell agency

2012 Disease Team 1 Update

Presentation to ICOC March 21, 2012

Agenda Item # 11

Overview - CIRM’s Disease Team 1 • Summarize current status of CIRM’s 14 Disease Teams

as of March 2012 – Context of Disease Team programs at CIRM – Brief outline of each Disease Team project – Key progress and accomplishments to date – Status of their progress towards filing a successful IND within 4

years – Budget allocated – Process for assessment

Disease Teams align with CIRM’s mission and clinical strategic objective • CIRM’s mission is to advance stem cell research for the

discovery and development of cures, therapies, diagnostics and research technologies to relieve human suffering from chronic disease and injury.

• Key strategy to progress stem cell science into clinical trials, CIRM funded 14 multidisciplinary Disease Teams in 2010 – Initiate the development studies, potentially leading to

successful filing of an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA) for these stem cell based therapies to enter human clinical trials over the next 4 years

CIRM Programs cover product development spectrum

Fundamental Biology

Early Translational Research I,II,III

Disease Team Research I

Disease Team Research II

Targeted Clinical Development

File IND

CandidateDiscovery Research

Phase 1 Clinical

Research

Phase 2 Clinical

Research

Basic Research Research

Preclinical Research

Preclinical Dev.

Select Development

Candidate (DC)

Preclinical Proof of

Concept (POC)

Transplantation Immunology

Tools & Technologies

CIRM Translational Portfolio

• 43 grants (Early Translation I, II; Disease Team I) – 14 (Disease Team I) target an Investigational New Drug (IND) filing

– 20 (Early Translational I, II) target identification and selection of a Development Candidate (DC)

– 9 (Early Translational II) conduct a subset of the studies to identify a development candidate or a feasible development candidate

• Cancer and neurodegenerative are the most represented

– Cancer (8 awards: 5 Disease Teams & 3 Early Translational)

– Neurodegenerative (14 awards: 2 Disease Teams and 12 Early Translational)

CIRM’s Disease Teams, addressing major unmet clinical needs, are moving towards the clinic

Eye Disease (1)

HIV/AIDS (2)

Blood Disorders (1)

Cardiac Disease (1)

Diabetes (1)

Skin Disease (1)

FILE IND

Discovery Research Clinical Research

Preclinical Dev.

DEVELOPMENT CANDIDATE

Preclinical Research Basic Research

Cancer (5)

Neurological Disorders (2)

Discovery Research

Early Clinical

Research

Preclinical Dev.

Preclinical Research

Basic Research

Disease Team 1 Overview Grant/PI Proj Start Total Award Current Status DR1-01421/Aboody 3/2010 18,015,429 Continue DR1-01426/Berger 4/2010 19,162,435 Terminating 3/31/2012 DR1-01430/Carson 3/2010 19,999,826 Continue with revisions DR1-01444/Humayun 4/2010 15,904,916 Continue DR1-01477/Slamon 5/2010 19,979,660 Continue DR1-01485/Weissman 3/2010 19,317,614 Continue DR1-01471/Goldstein 6/2010 11,500,429 Continue DR1-01461/Marban 3/2010 5,560,232 Continue DR1-01431/Chen 6/2010 19,999,580 Continue DR1-01452/Kohn 3/2010 9,212,365 Continue DR1-01454/Lane 5/2010 11,709,574 Continue DR1-01423/Robins 2/2010 19,999,937 Continue DR1-01480/Steinberg 2/2010 20,000,000 Continue DR1-01490/Zaia 5/2010 14,583,187 Continue

Milestones and expert advice, to better position the Disease Teams (DTs) for success

• After ICOC approval and before funding, CIRM and DTs agreed on Go/No Go and progress milestones and criteria to inform decisions; budget to support proposed activities

• Complementing quarterly and annual reporting with CIRM, DTs met with CIRM and panels of clinical development advisors at 12 to 18 months of their progress; will continue to meet on annual basis

• Convening of clinical development advisors to provide external input into milestone process was approved in concept plan for DT solicitation, identified in the DT RFA, and subsequently communicated to all of the DTs

– To prevent even the appearance of conflict of interest (COI), CIRM applied GWG COI rules. Clinical development advisors who had a financial, professional or personal COI with respect to one of the awards were disqualified from participating in the panel’s deliberations

Clinical development advisor panels, process for assessing DTs • Clinical development advisor panels are composed of experts in

product development – preclinical and clinical research, process development and manufacturing,

regulatory standards, stem cell/disease-specific biology, disease-specific clinical expertise, and commercial relevance

• Provided advice and recommendations on project strategy, progress in meeting goals and go/no-go decision points, and approaches to meeting challenges in their product development plans

• Recommendations provided to Senior Vice President, Research and Development, and CIRM considered this advice in subsequent internal deliberations about the merit of continued support, and under the guidance of the President, made final decisions and followed-up with the DTs on these issues

Advisors Deborah Armstrong, MD Johns Hopkins Kimmel Cancer Ctr

Howard Fine, MD Nat’l Cancer Inst; Nat’l Inst Neurol Disorders and Stroke

Jonathan Auerbach, PhD GlobalStem

Joyce Frey-Vasconcells Pharmanet

Merry Lee Bain, MS Partner, NDA Partners, LLC

Derek Hei, PhD Univ of Wisconsin

Nessan Bermingham, PhD BioEquity Capital, LLC

Anthony Hollander, PhD Univ of Bristol

Lauren Black, PhD Charles River Laboratories

Daniel Hoth, MD Hoth Consulting, Inc

Rajesh Chopra, PhD, BSc; MBBS;FRCP, FRCPath Celgene Corporation

Judith Karp, MD Johns Hopkins Kimmel Cancer Ctr

Alan F. Cruess, MD, FRCSC Dalhousie University

Robert Langer, ScD Massachusetts Inst. of Technology

David T. Curiel, MD, PhD Wash Univ School of Medicine

Edith P. Mitchell, MD, FACP Kimmel Cancer Ctr at Jefferson

Advisors Bruce Montgomery, MD CEO Cardeas Pharma

Ed Stanley, PhD Monash University

Jon Odorico, MD Univ of Wisconsin

Eckhard Thiel, MD Univ Berlin

Raymond Roos, MD Univ of Chicago

Jeffrey Touchman, PhD Arizona State University

Michel Sadelain, MD, PhD Memorial Sloan Kettering Cancer Center

Darin Weber, PhD Mesoblast

David Savello, PhD XenoPort, Inc

James Wilson, MD, PhD Univ of Pennsylvania

Sean Savitz, MD Univ of Texas

Wolfram Zimmermann, MD University Medical Center Gottingen

11

Collaborative Funding Partners on 4 of the 14 DTs

UK Canada Catriona Crombie Medical Research Council

Karen Dewar, PhD Genome Canada

Robert Buckle, PhD Medical Research Council

Stephane Pion, MD, PhD CIHR Inst of Cancer Research

CIRM Science Officers involved in day to day management of DTs

Karen Berry, DVM, PhD Pat Olson, PhD

Ingrid Caras, PhD Bettina Steffen, MD Sohel Talib, PhD

Also providing Scientific support : Zach Scheiner, PhD Kevin Whittlesey, PhD

DR1-01421 Aboody Recurrent Glioblastoma (brain tumor) • Therapeutic candidate

– Allogeneic hNSC line to target tumors, engineered to deliver enzyme, carboxylesterase, to convert chemotherapy drug CPT-11 to more potent metabolite SN-38, at the site of the invasive tumor

• Key Accomplishments – Select final therapeutic candidate, develop under good manufacturing

practices for the clinic – Investigated optimal route, dose of NSC to achieve max % of tumor

coverage – will inject intracranial; also develop intravenous approach – 1000 fold more toxic to brain tumor cells than chemotherapy alone – Developed novel iron nanoparticle track stem cells, non-invasive imaging – 1 publication, two under review, 11 presentations – Founded company, TheraBiologics

• Status – Complete preclinical POC efficacy fall/2012, and pre-IND discussion with

FDA; no financial or timeline impact to project at this time

DR1-01426 Berger Recurrent Glioblastoma (brain tumor) • Therapeutic candidate

– Allogeneic hNSC or MSC (from best of 3 sources) to target tumors, engineered to deliver gene product toxic to tumors (2 distinct gene modifications - TRAIL or cytosine deaminase and suicide gene)

• Key Accomplishments – Stem cells did not reach brain tumors by intravenous route – NSCs and MSCs delivered directly to tumors similar dispersion in tumor – Unmodified NSCs had insufficient proliferative capacity for production as

therapeutic stem cells – In vitro studies showed superior anti-tumor activity when stem cells

modified with cytosine deaminase in presence of pro-drug 5FC, compared to TRAIL; in vitro anti-tumor activity of CD + UPRT more rapidly produces toxic metabolites than CD alone

– 2 publications, developed 2 methods for detecting human cells and xenograft preclinical model for use in therapeutic testing

• Status – not able to select a cell candidate according to selection criteria – no go; terminating 3/31, and estimated savings $13M

DR1-01430 Carson Cancer stem cells in Leukemias • Therapeutic candidate

– 3 small molecules and 3 monoclonal antibodies against CSCs in acute (T-ALL, B-ALL, AML) and chronic (CLL, CML) leukemias; team is working with Canadian CFP (John Dick -Toronto) to dev therapies targeting specific survival and self-renewal pathways in leukemic stem cells

• Key Accomplishments – Shown efficacy with anti-ROR1 monoclonal antibody blocking Wnt5

signaling in CLL stem cells, and with small molecule inhibiting JAK2 kinase in AML in rigorous serial transplant models in preclinical models using patient leukemia cells

– conducting extensive genomics studies to dev leukemia stem cell biomarker signature of response/resistance for potential utility in individualizing therapies and improving response

• Status – CIRM recommended team focus their work on two candidates and two

diseases (anti-ROR1 in CLLand JAK2 inhibitors in AML); budgets and timelines being assessed and realigned accordingly

DR1-01444 Humayun Age-related macular degeneration • Therapeutic candidate

– hESC derived retinal pigment epithelium (RPE) on synthetic matrix; matrix mimics membrane at back of the eye - important for attachment, survival and differentiation of RPE (intact RPE imp for photoreceptors and vision). UK MRC CFP (Peter Coffey)

• Key Accomplishments – Design ultra-thin matrix ,sufficient mechanical strength for culturing and

surgical handling; permeability characteristics mimic membrane back of eye (Bruch’s membrane), allows passage of proteins, prevents migration of stem cells

– 7 patent filings covers the matrix, placement of cells on matrix, methods to produce RPE, method to track cells after implantation and specialized instrumentation for surgical delivery of the implant

– POC after implantation in preclinical model, showed successful interdigitation of transplanted RPE/matrix with host photoreceptors, with morphological and functional rescue of photoreceptors, rescue of vision

– Spin-off company Regenerative Patch Technologies • Status – Timelines and financials unchanged

DR1-01477 Slamon Cancer stem cells in solid cancers • Therapeutic candidate

– Novel small molecule inhibitors of 2 kinases, targeting CSCs in glioma, colon carcinoma and ovarian cancer. Working in collaboration with Canadian CFP (Tak Mak – Toronto)

• Key Accomplishments – First lead candidate molecule has shown efficacy in preclinical models

using human tumors and specifically targeting CSCs, and is moving into IND-enabling studies. Team is working on a second molecule targeting a different novel pathway in CSCs.

• Status – Timelines and financials unchanged

DR1-01485 Weissman Cancer stem cells in acute leukemia • Therapeutic candidate

– Hu anti-CD47 monoclonal Ab, directed against cell surface target preferentially expressed on acute myeloid leukemia/ other CSCs. CD47 functions as a “don’t eat me” signal by binding to a receptor on phagocytic macrophages and inhibiting their signaling. UK MRC CFP (Paresh Vyas - UK)

• Key Accomplishments – Humanized and evaluated a number of candidate anti-CD47 antibodies aimed

at CSC in acute myelogenous leukemia(AML) – Filed patent covering sequence, uses for their lead therapeutic candidate – POC efficacy, eradicated leukemia in tumor-bearing xenograft model of

primary leukemic cells from patients with AML – Conducting preclinical dose exploration and pilot safety studies – MRC funded UK component collecting/analyzing samples from patients

enrolled in AML trials to evaluate diagnostic and prognostic value of CD47 and other markers of interest re: drivers of leukemia relapse

• Status – Pursuing preclinical safety and efficacy; timelines and financials unchanged

DR1-01471 Goldstein Amyotrophic Lateral Sclerosis (ALS) • Therapeutic candidate

– hESC derived astrocyte precursor cells for subsequent development of product to inject into ALS patient’s spinal cord

• Key Accomplishments – Generated cells from different sources of hESCs and are in the process of

identifying cell lines with best characteristics of minimal toxicity and efficient production of final cell type

– POC demonstrating hESC-derived neural stem cells can protect motor neuron viability in preclinical model

• Status – On track for selecting a single cell line in mid- 2012; timelines and

financials unchanged

DR1-01461 Marban Advanced ischemic cardiomyopathy • Therapeutic candidate

– Autologous cardiac-derived cardiospheres (CSps) or cardiosphere-derived cells (CDCs) for advanced ischemic cardiomyopathy (heart failure)

• Key Accomplishments – Discovered that allogeneic cells appear to be as effective as autologous

cells in improving cardiac function in preclinical model, and immune consequences of allogeneic appear to be neglible, and with CIRM support, extended that finding to another preclinical model

– Allogeneic cells can be obtained in large numbers from donor heart, greatly facilitating scale up and manufacture, enabling highly standardized “off the shelf” product; CIRM approved switch towards an allogeneic product

– Selected CSps as therapeutic candiaate and will deliver them by direct injection in to the heart using a special magnetically-guided catheter

• Status – IND filing for allogeneic product anticipated in mid-2012; no change in

timeline or financials.

DR1-01431 Chen HIV/AIDS • Therapeutic candidate

– Autologous hematopoietic stem cells (CD34+) genetically modified with lentiviral vector encoding short hairpin RNA against CCR5 and HIV fusion inhibitor for patients with HIV infection, consider patients with AIDS/lymphoma

• Key Accomplishments – Identified unique anti-HIV small RNAs to prevent HIV infection through

preventing HIV entry into cells by targeting CCR5 as well as HIV replication through inhibiting different steps of HIV replication cycle. Ongoing studies demonstrate HIV inhibition both in vitro as well as in vivo preclinical model.

• Status – – No impact on timelines and financials at this time

DR1-01452 Kohn Sickle cell diseases • Therapeutic candidate

– Autologous human bone marrow hematopoietic stem cells (HSC) genetically modified using lentiviral vector encoding anti-sickling human b-globin for patients with sickle cell disease

• Key Accomplishments – Selected the single therapeutic candidate with disease modifying activity

demonstrated in vitro and in vivo preclinical model, has had their pre-IND meeting with the FDA, and are planning preclinical toxicology studies

– Presented results of ongoing studies at the American Society of Hematology annual meeting in San Diego in December 2011

• Status – If team is able to demonstrate feasibility of obtaining sufficient numbers of

CD34+ cells by dual bone marrow harvest then there will be no impact on timelines and financials. The team has already done preclinical POC studies with bone marrow derived CD34+ cells. Other activities will continue as planned.

DR1-01454 Lane Dystrophic epidermolysis bullosa (DEB) • Therapeutic candidate

– Autologous iPSC-derived, gene-corrected keratinocytes; DEB is caused by mutations in type VII collagen, and team is targeting 2 forms of DEB, the recessive form and dominant form.

• Key Accomplishments – Team has successfully generated iPSC lines from several patients with

the recessive form of DEB • Status

– No immediate impact on timelines or financials

DR1-01423 Robins Type 1 Diabetes • Therapeutic candidate

– Allogeneic hu ESC-derived pancreatic progenitors, mature in vivo to beta cells secreting insulin in response to glucose, delivered in retrievable immunoisolation device implanted subcutaneously

• Key Accomplishments – Prototypes tested in preclinical model; in preclinical POC studies, this cell-

device combination cured drug-induced diabetes – ViaCyte established cell mfr, device mfr proceeding at a scale, level of quality

to enable preclinical, clinical testing of the combo product; specifically: • made, qualified cGMP master cell bank that met defined criteria; made cGMP working cell

bank; finalized progenitor cell manufacturing process, determined final device configuration for clin testing; device manufacturing facility was designed and built; established preclinical models in collaboration with world-renowned immunologists and testing ability of device to protect cells from allo- and auto-immunity; preparing for pivotal IND enabling studies; developing clinical plan for FIH testing

• Two invention disclosures • Status – received suppl funding from JDRF; in discussion with potential partner;

CIRM needs to consider providing bridging funds to support activities needed to support IND filing within the 4 year period of award

DR1-01480 Steinberg Stroke • Therapeutic candidate

– Allogeneic hESC derived NSC line transplanted alone or in combination with matrix material into infarcted area of brain, with concomitant immunosuppression

• Key Accomplishments – Utilizing research bank of candidate cells, functional recovery

demonstrated in 3 preclinical models of stroke in 3 independent labs – Continues to establish cell mfr and testing processes to enable preclinical

and clinical testing; produced 2 qualification lots that can be elected as master cell bank and working cell bank, based on extensive characterization, func and safety testing

– Conducted pre-pre-IND meeting with FDA – Pursuing less complex mfr process (without hydrogel) in order to bring

candidate to IND and FIH testing expeditiously (exploring hydrogel as part of CIRM tools and technology award to optimize technology)

• Status – no impact to original timelines and financials at this time

DR1-01490 Zaia HIV/AIDS • Therapeutic candidate

– Adenovirus modified hematopoietic stem cells (CD34+) expressing zinc finger nuclease targeting CCR5; targeted to AIDS leukemia patients infected with CCR5 tropic HIV and undergoing autologous HSC transplantation; ultimately, as method is improved using non-ablative HSC transplantation, this indication would expand to include AIDS patients with retroviral drug failure

• Key Accomplishments – Optimizing methods for adenoviral vector mediated transduction of HSCs and

CCR5 disruption; optimized methods for expression of ZFN in HSCs to target CCR5

– Dev preclinical model to test stem cell therapy for HIV • Used ZFN to alter CCR5 gene in HSCs, and demonstrated these cells can be transplanted

into preclinical model. CCR5 gene encodes cell surf receptor used by HIV to enter cells. When altered HSCs given to preclinical model that lacked effective immune system, cells colonized in bone marrow and created new blood system with mutated CCR5. When exposed to HIV, recipients beat it back.

• Status – progressing towards IND enabling studies for scale up cell processing; no imp-act on timelines or budget; clinical dev advisor meeting planned for Q4 2012

Disease Team portfolio

Disease Area, # Projects (n = 14)

Disease Area, CIRM Investment ($225.6 MM)

Disease Area, CIRM & CFP Investment ($270.4 MM)

Back up

Eye Disease

Progression of age-related macular degeneration, from www.clevelandsightcenter,org

Award Goal Disease Approach DR-1444 USC, UCSB Univ. College London (UK)

IND Age-related Macular Degeneration

(Dry form)

Allogeneic functionally polarized hESC-derived RPE monolayers on synthetic substrate implanted sub-retinally

TR-1219 Scripps Res. Institute

DC Age-related Macular Degeneration (Dry

form)

Autologous iPSC-derived RPE (generated without integrating vectors)

TR-1272 UCLA

DC Age-related Macular Degeneration (Dry

form)

Autologous adult SC (CMZ) or iPSC-derived RPE +/- ex vivo engineering to express negative regulators of complement cascade

Eye Disease

Progression of Retinitis Pigmentosa, from www.medgadget.com

Limbal stem cells

Limbal epithelial stem cells reside in the basal layer of the epithelium, from GA Secker NCBI Bookshelf

Award Goal Disease Approach TR-1794 UCI

DC Retinitis Pigmentosa

Allogenic retinal progenitor cells

TR-1768 UCLA

POC Limbal stem cell deficiency

Ex vivo expansion of corneal epithelial stem / progenitor cells also known limbal stem cells (LSC)

Cancer

A child is stricken with leukemia, from infomationhealth.blogspot.com

Award Goal Disease Approach DR-1430 UC San Diego; Uni Health Network (Canada)

IND Hematologic malignancy (AML, CML, ALL, CLL)

Existing candidate molecules (3 small molecule, 3 MAb) targeting leukemic stem cells (LSC) by blocking survival and self-renewal pathways that function preferentially

DR-1485 Stanford University; Weatherall Institute, Oxford Univ. (UK)

IND Hematologic malignancy (AML)

Monoclonal antibody against CD47 – “Don’t eat me” antigen that is expressed on LSC and inhibits their phagocytosis by macrophages

Award Goal Disease Approach TR-1789 UCSD

DC Hematologic malignancy (CML)

Small molecule pan BCL-2 inhibitor targeting LSC

TR-1816 Children;s Hospital of L.A.; Univ. of Jena (Germany)

DC Hematologic malignancy (AML,

ALL)

Small molecule inhibitor of BCL6 targeting LSC

Cancer

A small-molecule drug selectively kills tumor cells by activating p53 protein, from www.cancer.med.umich.edu

Cancer

A dividing cancer cell, from www.integraldeeplistening.com

Award Goal Disease Approach DR-1477 UCLA; Stanford Univ., USC, Univ. Health Network (Canada)

IND Solid tumors (Colon cancer, ovarian cancer,

glioblastoma)

Small molecules specific for either of two drug targets in cancer stem cells (CSC)

A confocal image showing β-crystallin (green), a small heat shock protein in the perinuclear Golgi in dividing human U373 glioblastoma cells, from S.P. Bhatt UCLA

Cancer

An image of glioblastoma brain tumor, from WikiCommons

A glioblastoma multiforme cell, from www.radiologia.blog.hu

Award Goal Disease Approach DR-1421 City of Hope Med. Center

IND Recurrent Glioblastoma

Allogeneic established hNSC line to target tumor, engineered ex vivo to deliver carboxylesterase to locally convert CPT-11 to SN-38

DR-1426 UCSF, Ludwig Instit. for Cancer Res., Sanford-Burnham Instit. for Medical Res.

IND Recurrent Glioblastoma

Allogeneic hNSC (hMSC) to target tumor, engineered ex vivo to deliver a tumorcidal gene product (TRAIL or cytosine deaminase, and a suicide gene)

TR-1791 UCLA

DC Solid tumor (Glioblastoma)

Tumor homing by MSC genetically engineered to produce replication competent retrovirus encoding a suicide gene

Cardiovascular

Award Goal Disease Approach DR1-01461 Cedars-Sinai Med. Center

IND Advanced Ischemic

Cardiomyopathy (heart failure)

Autologous cardiac derived, ‘cardiospheres’, expanded and delivered by direct catheter injection into heart muscle

TR1-01249 Stanford University DC

Multiple (Stroke, Heart disease, Skin

ulcers, Bone fractures)

Recombinant Wnt in a sustained release formulation to stimulate endogenous stem cells to repair tissues

Neurological Disorders Neurodegenerative Disease

Award Goal Disease Approach

DR1-01471 UCSD, Salk Institute IND ALS

Allogeneic hESC-derived astrocyte precursors delivered into spinal cord (delivery device)

TR1-01267 Sanford-Burnham Institute; Howard Florey Institute (State of Victoria, AS)

DC Parkinson’s Disease

The best of either hNSC derived from tissue, ESC, or iPSC; or hVM (ventral mesencephalon) precursors derived from ESC, NSC, or tissue

TR2-01856 Buck Institute; City of Hope National Medical Center

DC Parkinson’s Disease

Allogeneic hPSC-derived dopaminergic neurons

TR2-01778 Salk Institute; University of Erlangen (BMBF, Germany)

POC Parkinson’s Disease

Small molecule modulator of neuro-inflammation identified by screening on astrocytes/microglia from patient-derived iPSCs

Neurological Disorders Neurodegenerative Disease

38

Award Goal Disease Approach

TR1-01245 UCI, Monash University (State of Victoria, AS)

DC Alzheimer’s Disease

Allogeneic hESC-derived NSC or hESC-derived NSC genetically modified with a beta-amyloid degrading enzyme or a transcription factor that promotes neuronal differentiation for transplantation

TR1-01257 UCD DC Huntington’s Disease

Allogeneic MSC engineered ex vivo to express siRNA targeting mutant huntingtin mRNA. Injected intracranially

TR2-01841 UCI DC Huntington’s Disease Allogeneic hESC-derived neural stem

or progenitor cells for transplantation

Neurological Disorders

Award Goal Injury Approach

TR2-01785 UCLA POC Spinal Cord

Injury Allogeneic hESC-derived motor and autonomic precursor neurons

DR1-01480 Stanford University, UCLA

IND Stroke Allogeneic hESC-derived NSC line transplanted alone or in combination with matrix

TR2-01767 UCI POC Traumatic Brain

Injury Allogeneic hESC-derived NSC

Neurological Disorders

Award Goal Disease Approach

TR2-01844 iPierian, Inc. DC Spinal Motor

Atrophy

Small molecule that increases SMN1 gene product in patient iPSC-derived motor neurons

TR2-01832 City of Hope National Medical Center, University of Bonn (BMBF, Germany)

POC Canavan Disease

Autologous iPSC-derived neural or oligodendrocyte progenitors, genetically modified to correct mutant (aspartoacylase) ASPA gene

TR2-01814 UCSD POC Autism Spectrum

Disorders

Neurons from ASD (and control) iPSC for phenotype screening, assay development and validation, drug screening and biomarker identification

TR2-01749 UCSD POC Refractory

Epilepsy

Allogeneic hESC-derived progenitors from GABAergic inhibitory neurons analogous to those in medial ganglionic eminence

Diabetes & Complications

41

Award Goal Disease Approach

DR1-01423 ViaCyte Inc., UCSF

IND Diabetes

Allogeneic hESC-derived pancreatic cell progenitors in a device implanted subcutaneously that mature in vivo to beta cells that secrete insulin in response to glucose. Transient immunosuppression.

TR2-01787 UCD, Technical University of Munich (BMBF, Germany)

DC Chronic diabetic foot ulcers

Allogeneic hMSCs on a dermal regeneration scaffold

HIV/AIDS

Award Goal Disease Approach

DR1-1431 UCLA, Calimmune, Inc.

IND AIDS Lymphoma

Autologous HSC transduced ex vivo with a lentiviral vector engineered to express a shRNA against CCR5 & fusion inhibitor. IV administration after myeloablation.

DR1-1490 City of Hope National Medical Center, USC, Sangamo Biosciences

IND AIDS Lymphoma

Autologous HSC transduced ex vivo with non-integrating vector engineered to express zinc finger nuclease against CCR5. IV administration after myeloablation

TR2-1771 City of Hope National Medical Center

DC AIDS Lymphoma

Autologous HSC genetically modified ex vivo with multiple anti-HIV resistance genes and a drug resistance gene

Blood, Genetic Disorders

Award Goal Disease Approach

DR1-01452 UCLA, Children’s Hospital, LA

IND Sickle Cell Anemia

Autologous HSC, genetically corrected ex vivo by lentiviral vector mediated addition of a hemoglobin gene that blocks sickling. IV administration after myeloablation

TR1-01273 Salk Institute DC Fanconi Anemia,

X-SCID Autologous iPSC-derived HSC genetically corrected by homologous recombination

DR1-01454 Stanford University IND

Dystrophic Epidermolysis

Bullosa

Epidermal sheets from expanded autologous genetically corrected (to express wild type COL7A1) iPSC-derived keratinocytes

TR2-01756 Stanford University POC Duchenne muscular

dystrophy

Autologous skeletal muscle precursor cells derived from human iPSCs genetically modified to correct the dystrophin gene

CIRM Industry Engagement Initiatives

• CIRM researchers to be featured • Premier event for regenerative

medicine industry

Regenerative Medicine Pharma & Investor

Partnering Conference

• Offers a streamlined procedure to

provide funding to programs demonstrating commercial validation

Strategic Partner Funding Program

Patent funding and Technology Transfer

Support

$5 M allocated for technology transfer support; program being developed