The state stem cell agency September RFA 10-05: Disease Team Therapy Development Research Awards Educational Webinar September 9, 2011 Ellen G. Feigal, M.D. Vice President, Research and Development California Institute for Regenerative Medicine

Webinar objective is to help address your questions as you prepare your application We will review the following: –Goals and intent of the RFA –Context of this initiative within CIRM’s portfolio –Eligibility criteria e.g. of therapeutic candidate, Principal investigator, and Institution –Review Criteria by which the award will be assessed –Templates to guide your organization of the material to help ensure a complete submissions package September 9, 20112

Webinar objective is to help address your questions as you prepare your application We will review the following: –Exceptions pathway for for-profits, other special issues –Opportunity with collaborative funding partners from Canada (CSCC), Germany (BMBF), and Spain (Andalucia) –Time frame for submission, exceptions request, supplemental information, Grants Review Group review, and anticipated ICOC assessment September 9, 20113

Purpose is to advance preclinical and/or early clinical development of stem cell-based therapies Purpose of this RFA is to advance preclinical and/or early clinical development of novel therapies, derived from or targeting stem cells or utilizing direct reprogramming, that may lead to new and more efficacious treatments for patients with debilitating disease or serious injury. Goal of the DTTD is to achieve, within the 4 year time frame of the research award, one or more: –Submit a well-supported IND for a clinical study –Complete a Phase I or Phase I/II study –Complete a Phase II study 4 September 9, 2011

Where does this RFA fit in CIRM’s current portfolio programs Fundamental Biology Early Translational Research I,II Disease Team Research I Disease Team Research II Targeted Clinical Development File IND Candidate Discovery 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) 5 Translational Portfolio, Current September 9, 2011

CIRM’s translational portfolio is growing 44 grants (Early Translation I, II; Disease Teams I and Targeted Clinical Development) –1 Early stage clinical trial –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 6 September 9, 2011

Provide compelling evidence for your approach CIRM has made substantive investments across a broad number of therapeutic areas, with largest in neurological diseases, cancer, HIV/AIDS and eye diseases – see appendix A Applicants proposing a project substantially similar to one already represented in CIRM’s translational portfolio must provide compelling evidence for their approach September 9, 20117

Scope criteria - must be cell-based, single therapeutic candidate Cell therapy candidate derived from/utilizing hESCs, hiPSCs, neural stem cells, neural progenitor cells, or reprogrammed/genetically-modified stem cells Small molecule or biologic candidate characterized or generated using stem cell types above Candidate that targets cancer stem cells or endogenous stem cells in vivo Engineered functional tissue candidate for transplantation Outside of Scope and Specifically Excluded: –minimally manipulated bone marrow cells; mesenchymal stem cells; umbilical cord blood stem cells; adipose-derived stem cells; and hematopoietic stem cells 8 September 9, 2011

Therapeutic candidate must meet criteria Suitable for use in humans, completed all the research necessary to initiate IND-enabling preclinical development required for regulatory approval for testing in humans. Projects further along in the development pipeline are also eligible –Suitable for use in humans (i.e., must use human, not animal cells); –Compelling, statistically significant, reproducible disease modifying activity with adequate controls in (multiple) relevant in vitro and in vivo models; –Preliminary assessment of potency, dose, formulation, stability and safety (includes immunogenicity, if applicable) completed; –Evidence for potential mechanism of action; –Research assays developed to characterize the candidate (e.g., for identity, purity and activity); 9 September 9, 2011

Therapeutic candidate must meet criteria Methods developed for reproducible production of a defined therapeutic candidate (including viral vector, if applicable) at yields adequate to conduct IND enabling studies; Candidate compatible with cGMP (Current Good Manufacturing Practices) (e.g. for a cell therapeutic, derivation and maintenance adequately documented); Site, mode and method of delivery selected and/or under development. 10 September 9, 2011

Eligibility criteria for PI and institutions Only PIs and applicant institutions who have received a Planning Award are eligible to apply, with two exceptions: For-profit applicant institutions and recipients of Disease Team I Research Awards (RFA 09-01) may apply for an exemption from the Planning Award requirement, provided that they meet specific criteria September 9,

For-profit applicants – exception pathway For-profit entities without a funded planning award may request permission to apply. To qualify for consideration, they must meet the following criteria: –Therapeutic candidate must be in scope and evidence is provided that it meets the eligibility criteria –Evidence is provided that a multidisciplinary team (which may all be employed by the for-profit applicant) containing all appropriate functional groups for the proposed project has been assembled. All necessary partners (Co-PI, Partner PI), and collaborators have been identified and are willing to participate in the project if recommended for funding. September 9,

For-profit applicants – exception pathway Proposals seeking CIRM funding for clinical trials are highly encouraged to provide evidence that additional funds (minimum of 50% of the total funds) for the proposed project have been secured or will be secured if recommended for funding. For-profit entities seeking permission to apply under these terms must submit: –an Exception Request Form (Adobe PDF), available on CIRM’s web site ( and a letter (not exceeding 5 pages) briefly describing the therapeutic candidate, target indication/patient population, proposed preclinical and/or clinical trial(s) and address all eligibility criteria. September 9,

Disease Team 1 applicants - exception pathway DT1 applicants must have completed an IND filing that is ready to begin Phase I clinical trials by summer of 2012 with the therapeutic candidate that is the subject of the DT 1 award. Evidence is provided that a multidisciplinary team containing all appropriate functional groups for the proposed project has been assembled. All necessary partners (Co-PI, Partner PI), and collaborators have been identified and are willing to participate in the project if recommended for funding. September 9,

Disease Team 1 applicants - exception pathway Proposal seeking CIRM funding for clinical trials are highly encouraged to provide evidence that additional funds (minimum of 50% of the total funds) for the proposed project have been secured or will be secured if recommended for funding. The therapeutic candidate must meet all scope requirements and provide evidence that the therapeutic candidate proposed meets all required criteria. September 9,

Disease Team 1 applicants - exception pathway Disease Team I applicants seeking permission to apply under these terms must submit: –an Exception Request Form (Adobe PDF) available on CIRM’s web site ( and a letter (not exceeding 5 pages) briefly describing the therapeutic candidate, target indication/patient population, proposed clinical trial(s) and address all eligibility criteria. September4 9,

Reviewer criteria to assess the application Applications will be evaluated in six key areas: –Significance and Impact Reasonable draft Target Product Profile (TPP), Clinical Competitiveness and Impact, Responsiveness to RFA –Rationale Strong scientific rationale supported by compelling preclinical studies for the proposed therapeutic intervention in the target disease or injury –Therapeutic Development Readiness The project is sufficiently mature and its status is such that there is reasonable expectation that the stated project objective(s) can be achieved within 4 years of the project start date September 9,

Reviewer criteria to assess the application –Feasibility of the Project Plan Plan and goals feasible and adequate to meet the objectives of this RFA Plan proposes studies that address specific metrics (success criteria) defined for attributes of the TPP appropriate for the stage of development Project milestones describe key activities and deliverables. The project milestones are reliable indicators of the project's progress. The criteria for Go/No Go decisions are adequately defined and provide quantifiable measures of the project's performance. Project timeline is complete, highlights key progress and Go/No Go decision milestones and is realistic. September 9,

Reviewer criteria to assess the application –Principal Investigator and Development Team Possess relevant experience in regulated translational research and therapy development, with appropriately assembled team with key expertise, appropriate structure, function and plan for execution of project, and budget with appropriate rationale –Collaborations, Resources and Environment Necessary facilities, major equipment, and services are available; relevant assets available e.g., IP, licenses; collaborations and/or partnerships appropriate for the success of the project September 9,

Templates to guide the organization of your submission Templates are located in Part B of the application –Section 2 – CIRM Target Product Profile (TPP) –Section 3 – Summary of Nonclinical Testing –Section 4 – CIRM Clinical Protocol Synopsis –Section 5 – CIRM Manufacturing Plan Synopsis September 9,

21 CIRM’s Collaborative Funding Partners (CFP): Leveraging Expertise and Resources with Germany, Canada and Andalucia in this RFA Canada Victoria India Japan UK Spain Germany China Maryland NYSCF Andalucia Australia JDRF France September 9, 2011

Interested in a CFP project? See appendices for details To apply for a collaboratively funded project involving CIRM and a Collaborative Funding Partner (CFP), applicants must satisfy both the CIRM requirements and any additional requirements established by the applicable CFP. For more details on CFP requirements, please see Appendices C, D, or E. September 9,

CIRM’s Governing Board (ICOC) allocated up to $240 million for 12 awards 4 year awards, allocated up to a total of 12 awards up to a total of $240 million For-profit applicants seeking CIRM funding for clinical trials are highly encouraged to provide evidence that additional funds (minimum of 50% of the total funds) for the proposed project have been secured or will be secured if recommended for funding. Nonprofit applicants proposing clinical trials are encouraged to engage in partnership(s) with industry to leverage expertise and additional funds for the proposed project. These strategies are intended to leverage CIRM’s funds. September 9,

CIRM Key dates to remember* 24 Exceptions RequestOctober 4, 2011 (CIRM decision by November 15, 2011) Award Applications dueJan 25, 2012 Limited supplemental info dueMarch 13, 2012 GWG ReviewApril 2012 ICOC ConsiderationJune 2012 Earliest FundingAugust 2012 *CFPs may have additional requirements that impose some different dates on their applicants September 9, 2011

If you have additional questions, here are the people to contact For information about this RFA: –Sohel Talib, Ph.D. Science Officer California Institute for Regenerative Medicine Phone: (415) For information about the review process: –Gilberto R Sambrano, Ph.D. Senior Review Officer California Institute for Regenerative Medicine Phone: (415) September 9,