WIXLIB

MISSIONS TAT E M E N TAccelerating stem cell treatments topatients with unmet medical needs.Accelerating world class science to deliver transformativeregenerative medicine treatments to a diverse Californiaand worldwide in an equitable manner.CIRM 5 Y E A R S T R AT E G I C P L A N 7

Since its inception, CIRM’s mission and strategic goalshave stayed true to the spirit of Proposition 71 by strivingto rapidly advance stem cell and regenerative medicinetechnologies toward treatments and cures for patients’unmet medical needs.In 2006, CIRM’s first strategic plan and its missionstatement reflected the challenges and opportunitiesin the emerging field of stem cell and regenerativemedicine. The seminal paper on human inducedpluripotent stem cells had yet to be published. Secondgeneration CAR-T cell technology was showing promisein preclinical models but had not yet demonstratedits clinical potential. The 2006 mission statement thusfocused on the need to accelerate research of stemcell and regenerative medicine technologies whilemaintaining the highest medical and ethical standards.In 2016, as CIRM issued its final strategic plan of theProposition 71 era, the field had advanced considerablyafter several critical clinical milestones. CAR-T cellshad demonstrated preliminary clinical safety andefficacy for blood cancers. Gene therapies and genemodified cell therapies had showed clinical benefitfor rare monogenetic diseases. Pluripotent StemCell-based cell therapies had progressed to clinicalstudies. CIRM’s mission statement was thus modifiedto capture the urgency of accelerating translationalresearch and propelling more promising therapies intoclinical development. The re-stated mission statementdefined the 2016 strategic plan’s goals of acceleratingtranslational research and developing the resources toultimately support 50 new clinical trials in 5 years.CIRM 5 Y E A R S T R AT E G I C P L A NNow in 2021, as CIRM sets its vision for theProposition 14 era, its mission and strategic goalsmust reflect the current state of regenerative medicineand address the next decade’s challenges andopportunities. Today, the clinical benefit of stem cellsand regenerative medicine continues to be validated bythe hundreds of ongoing clinical trials and by the realworld use of approved therapies. New technologiessuch as CRISPR gene editing are showing clinicalpromises in genetic blood, eye and neurologicaldiseases as well as in cancer. Given the initial clinicalsuccess in rare blood diseases and oncology, stemcell and regenerative medicine technologies arebeing aimed at a broader range of diseases from raremonogenetic diseases to neurodegeneration, diabetes,and heart disease. As the field advances rapidly, it isimperative that the promise of regenerative medicine isrealized as accessible, transformative, real-life therapiesfor patients across a diverse California and worldwide. 8

With this mission as its “north star,” CIRM has set out anew strategic planthat seeks to address the challenges and opportunities presented bythe growing field of regenerative medicine.The strategy is organized into three major themes:AdvanceWorld Class ScienceDeliverReal World SolutionsProvideOpportunity for AllThe challenges, opportunities, and measurable 5-year goals related to each strategic theme are discussed below.CIRM 5 Y E A R S T R AT E G I C P L A N 9

Theme 1Advance World Class ScienceAdvance World Class ScienceTo advance world class science, CIRM will leverage collective scientific knowledge to inspirecollaborative research that addresses Californians’ unmet medical needs.5-year Strategic Goals: Develop next-generation technology competency hubsthat broadly empower and connect California’s researchecosystem Build knowledge networks that foster and advance noveldiscovery, translational and clinical research approachesThe field of regenerative medicine isadvancing rapidly, driven by novel researchtools and technologies that generateterabytes of data on human biology, buthas to date resulted in few demonstrablyeffective treatments for devastatingdiseases. This is particularly true fordiseases of the central nervous systemwhere the complex biology underpinningneuropsychiatric, neurodevelopmental, andneurodegenerative diseases is still cominginto focus and disease-modifying therapiesremain elusive. Several factors contributeto the limited scientific advancement inthese areas, including: 1) Lack of attentionand financial support (from non-profitand industry sectors) for high-risk/highreward research and therapy development,particularly in disease indications that arenot commercially viable (i.e., rare diseases)or are complex (i.e., CNS-related diseases),and 2) The siloed nature of biomedicalresearch and development. This strategicplan will address these key issues.CIRM 5 Y E A R S T R AT E G I C P L A NHigh-Risk/High-Reward Research Projects. CIRM iscommitted to maintaining and augmenting high-risk/high-rewardprojects, including rare diseases and neurological disorders.CIRM’s unique funding partnership model has providedpredictable, reliable, and progressive funding for projects thatwere considered too risky in their discovery stages for financialsupport from governmental institutions or industry 3. To date: In addition to the 76 CIRM-funded clinical trials, CIRMfunding of preclinical projects has enabled an additional 31clinical trials 4. Nearly 12% of CIRM’s clinical funding comprises high-risk/high-reward stem cell and gene therapy approaches forrare diseases. Almost a quarter of CIRM’s total funding has focused onneurological disorders 5 and 14% of its clinical portfoliocomprises CNS diseases. CIRM’s hiPSC repository has enabled studies in psychiatricdiseases: Broad Institute investigators have identified lines withextreme high and low polygenic risk scores for schizophrenia 6.In this strategic plan, and in line with the recommendations ofthe Strategic Scientific Advisory Panel 7, CIRM will maintain andaugment this commitment in 2 ways: 1) Continue the fundingmechanisms through the existing pillar programs; 2) Designinfrastructure that organizes and democratizes data throughknowledge networks and accelerates shared usage of specializedtechnologies through competency hubs. This strategy will bedeployed within the broad CIRM funding programs, but will initiallybe designed to enable a consortium approach to CNS research,including neuropsychiatric and neurodevelopmental disorders 8. 10

Theme 1Culture of Collaboration. CIRM is committed todevelop a systematic approach that fosters “teamscience.” Scientific research and therapy developmenthas always been driven by small teams or targetedcollaborations between research labs. On the otherend of the spectrum, large-scale collaborative effortsdriven by public and private stakeholders tend to befewer in number but have demonstrated successstories; the advent of cancer immunotherapies or therecent rapid development of COVID-19 vaccines beingtwo of the more prominent examples. Despite theprevalence of small and large-scale collaborative efforts,the biomedical research enterprise still functions insilos where valuable data, resources and expertise areselectively shared.In recent years, there has been a paradigm shiftunderway in this culture of biomedical research towardone of greater data and resource sharingand broader coordination of research activities.While data sharing is not a new concept by anymeans, the current patchwork of public and privatedata repositories has several limitations including lackAdvance World Class Scienceof data standardization, limited interoperability andlack of analytical toolkits. These limitations make itdifficult to access, combine and analyze the shareddatasets for meaningful research insights. To addressthese limitations, the NIH and other institutions andorganizations have established data sharing policiesand developed collaborative resource sharing. CIRMwill promote a culture of collaborative research byinvesting in the research and technology infrastructureto advance and facilitate sharing of unique resources(see section on competency hubs below) andmeaningful CIRM-funded research data (see sectionon knowledge networks below).Investments in technology competency hubs andknowledge networks will advance collaborativeworld class scientific research and fuel discoveriesthat could lead to translational and clinical candidates.This model would also support the potential for “reversetranslation,” where new knowledge gained from latestage translational and clinical research could beaddressed in discovery research which, in turn, couldresult in new translational and clinical programs.Knowledge NetworkFoundational InsightsDiscoveriesTreatments and CuresShared CompetenciesCIRM 5 Y E A R S T R AT E G I C P L A NBasic, Translational andClinical Research 11

Theme 1Advance World Class Science5-Year Strategic GoalsDevelop next-generation technology competency hubs that broadlyempower and connect California’s research ecosystemScientific progress relies on revolutionary andinterdisciplinary breakthroughs in technology. Cuttingedge methodologies such as CRISPR gene editing,human cell modeling of disease, machine learning,AI, and others could significantly enhance scientificdiscovery and accelerate therapy development.However, practical utilization of these innovationsoften requires upfront investment in technologies,iterative development and validation, standardization ofprotocols, and specialization in training and expertise.These barriers limit research access and can delaymaturation and widespread adoption of the technologyplatform. Individual academic institutions address thesebarriers with centralized core research facilities thatmake specialized equipment and provide accessibleexpertise and training broadly to the institution’sresearch labs and courses.9 Early in its history underProposition 71, CIRM had established 17 sharedresearch laboratories as core facilities for stem cellresearch and training, many of which arestill operational today. Proposition 14 re-establishesand expands the shared laboratories programs.CIRM will build on the shared laboratories modelto develop competency hubs that will acceleratehypothesis-driven research, translational andclinical development of regenerative medicinetherapies and workforce development in CIRM’spillar programs. The competency hubs willconcentrate and network domain-specific expertiseand innovation to develop, validate and broadly shareunique technology-driven competencies. Examplesof competency hubs could include human cellmodels of disease10, and/or gene editing resources.The competency hubs will offer expertise in noveltechnologies, trained personnel, training courses,equipment, and standardization of workflows to broadlyserve three functions: (1) innovate and improve on11 thetechnology core competencies to augment their impactfor CA researchers and to further support regenerativeCIRM 5 Y E A R S T R AT E G I C P L A Nmedicine research and development; (2) provide broadaccess to the shared resources, training, and protocols;and (3) support and facilitate collaborative researchapproaches across CIRM’s discovery, translationaland clinical pillars. Other forms of competency hubswill be incorporated into existing or planned CIRMstrategic infrastructure such as Alpha Stem CellClinics, Community Care Centers, and the CaliforniaManufacturing Network (Explained further in Theme 2,Deliver Real World Solutions).“Updating the technologicalcapabilities of existing sharedlabs and stimulating partnershipswith institutions that currentlylack such expertise will create andstrengthen close collaborationsand generate a robust network oftherapy discovery and delivery.”—Lawrence Goldstein, PhD, ICOC Board MemberGiven the rapidly growing and evolving nature of theregenerative medicine field, a critical function of thecompetency hubs will be to continuously innovate,develop and validate the core technologies incollaboration with the users and other competencyhubs in the network. The competency hubs willprovide inter-institutional access to the technologyby sharing facilities, training, equipment, materials,protocols, and/or expertise. For example, a diseasemodeling competency hub could provide accessto facilities, equipment and training programs forderiving or differentiating cell lines or it could sharethe differentiated cells and appropriate protocols with 12

Theme 1researchers across the state. The competency hubswill facilitate collaborative research approaches byadapting their technology and/or developing specializeddata and resource sharing mechanisms to facilitate theneeds of the CIRM-funded collaborative projects. Thecompetency hubs will also constitute part of the CIRMcollaborative ecosystem making all their data availablethrough the CIRM data infrastructure hub, also knownas CIRM Knowledge Platform, which is explainedfurther below.Advance World Class ScienceSome competency hubs could serve as a workforcetraining microcosm for local and neighboring institutions.Most California state universities and community collegeshave neither the financial nor experiential bandwidth forinnovative research, but they may harbor a potentialdiverse future workforce who could learn thesetechniques and utilize the technology platforms for smallscale research. CIRM’s network of competency hubs willexpand geographic access to diverse communities andprovide these institutions with a unique opportunity ofexposure to state-of-the-art platforms.Shared Stem Cell Laboratory at UCLASuccess Stories: First Generation Shared Research LaboratoriesUnder Proposition 71, a total of 17 Shared Research Laboratory grants were awarded to academic and nonprofit research institutes to provide dedicated laboratory space that was free of NIH support and equipped togrow and maintain hESCs, served as a shared resource with available core equipment and trained personnel,and in some cases, also provided specialized, hands-on training courses. Shared Labs were available notonly to stem cell scientists at the grantee institution but also to those from nearby institutions without suchfacilities. These dedicated, common laboratories encouraged optimal sharing among individual investigators,research groups and departments to foster a collaborative, multidisciplinary research environment, andpromote cost effectiveness. Many of these laboratories have sustained their activities beyond CIRM fundingthrough either fee-for-service contracts or other funding mechanisms and some have expanded theirservices. For instance, UCLA’s Shared Lab includes fully equipped GMP-GTP-compliant labs and USC’sspace contains core facilities for FACS, biological imaging, therapeutic screening, and tissue culture. In thisPlan, CIRM seeks to expand the Shared Lab model by creating networks of specialized and collaborativecompetency hubs that offer knowledge and best practices in innovative, next-generation technologies andcell and gene therapy development.CIRM 5 Y E A R S T R AT E G I C P L A N 13

Theme 1Advance World Class Science5-Year Strategic GoalsBuild knowledge networks that foster and advance noveldiscovery, translational and clinical research approachesIn recent years, funding agencies, publishers,foundations, and academic institutions have adoptedmore robust data management and data sharingpolicies. Even with these attempts, however, thereremains a great deal of ambiguity around how and whatto share, how to meet data sharing requirements andhow to harmonize data across the diversity of public andprivate repositories, all of which significantly limit datausability, scientific productivity, and clinical relevance.“Making such data sharingand analysis across CIRMprojects operational and widelyaccessible would leverageCIRM investments, servingthe biomedical researchenterprise broadly.”– Keith Yamamoto, PhD, ICOC Board MemberCIRM will build knowledge networks that facilitatesharing of CIRM-funded data, leverage high-valueexternal datasets and build robust analyticaltools to maximize the real world impact of CIRMfunded research. To do this, CIRM will first foster aculture of open science. CIRM will clearly define itsown requirements and incentives for well-developeddata management and sharing plans in CIRM-fundedprojects; it will coordinate with other funding agencies,publishers, and California academic institutions toharmonize, facilitate and reward effective data sharingpractices. It can network on the one hand withCIRM 5 Y E A R S T R AT E G I C P L A Npublishing groups to harmonize open science policiesand incentivize consortium authorship models, and withfunding agencies and institutions on the other hand tobuild professional reward systems for excellent teamscience contributions. This multi-faceted approach willgenerate a healthy ecosystem in which team scienceis incentivized and the appropriate resources aredeployed to achieve this goal12.The initial implementation of knowledge networkswill focus on accelerating collaborative CNSresearch approaches13 that could benefit the study ofneurological diseases, including psychiatric disorders.The CIRM knowledge network will facilitate effectivemanagement, standardization, sharing and analysis ofCIRM-funded research data14. The network will addressthe needs of the research community including basicbiology researchers, translational researchers,computational biologists, and clinicians on relevant datatypes, sharing methodologies and best practices, datagovernance policies and analytical needs. Data typeswill include a variety of omics datasets from CIRMfunded research projects and CIRM-fundedcompetency hubs.To fully leverage these data towards betterunderstand

In 2016, as CIRM issued its final strategic plan of the Proposition 71 era, the field had advanced considerably after several critical clinical milestones. CAR-T cells had demonstrated preliminary clinical safety and efficacy for blood cancers. Gene therapies and gene-modified cell thera