1. Michael Palazzolo UC CAI Face-To-Face Meeting October 14, 2013 University of California Center for Accelerated Innovation

2. Local and National Announcements Posted by UCLA on Sept 30, 2013 (day before the government shutdown) Aired October 1, 2013 CTSA CentralNBC Channel 4 News

3. Notice of Award Notice of Award: Key Points Year 1 Budget Period 9/26/13-7/31/14 Key Personnel 100-day Implementation plan due 10/25/13 Interim Progress Report in Year 1 due 3/1/14 Cost-share report due with FFR Program Steering Committee Meeting 10/29-10/30/13

4. Introductions

5. Contents Introduction to leadership Goals Governance Technology Solicitation & Selection Technology Development Skills Development

6. Michael Palazzolo, MD, PhD Center Director, UC CAI Professor, UCLA Leadership UC CAI Tomas Ganz, MD, PhD Center Associate Director Professor, UCLA

7. Leadership Executive Committee Lars Berglund, MD, PhD Director, UCLA Clinical and Translational Science Center Steven Dubinett, MD Director, UCLA Clinical and Translational Science Institute Gary S. Firestein, MD Executive Committee Chair Director, UCSD Clinical and Translational Research Institute Clay Johnston, MD, PhD Director, UCSF Clinical and Translational Science Institute Dan Cooper, MD Director, UCLA Institute for Clinical and Translational Science

8. Site Leaders Campuses June Lee, MD UCSF Shaun Coughlin, MD, PhD UCSF Sotirios Tsimikas, MD UCSD Joseph Witztum, MD UCSD Laura Marcu, PhD UC Davis Steven George, MD, PhD UC Irvine Tomas Ganz, MD, PhD UCLA

9. Domain Leaders Diseases June Lee, MD Lung and Sleep Diseases Shaun Coughlin, MD, PhD Cardiovascular Disease Sotirios Tsimikas, MD Cardiovascular Disease Tomas Ganz, MD, PhD Blood Disorders and Resources

10. Domain Leaders Platforms June Lee, MD Co-Leader, Therapeutics Shaun Coughlin, MD, PhD Co-Leader, Therapeutics Sotirios Tsimikas, MD Co-Leader, Diagnostics Joseph Witztum, MD Co-Leader, Diagnostics Laura Marcu, PhD Co-Leader, Devices and Tools Steven George, MD, PhD Co-Leader, Devices and Tools

11. Domain/Site Leaders At least one site leader for each campus At least one domain leader for each platform (drugs, devices, diagnostics) and disease (heart, lung and sleep, blood) Ensure the pool of candidate technologies is large Oversee proposal solicitation process Recruit study sections Recruit and oversee project development teams on respective campuses

12. Skills Development Program Catalogs entrepreneurial course offerings on all five campuses Matches innovators to mentors Conducts webinars, symposia Vish Krishnan Leader, Skills Development Program UCSD

13. Goals Goal 1 Engage University of California heart lung and blood disease innovators through a comprehensive education, training and mentorship program.

14. Goals Goal 2 Solicit and select technologies with high commercial potential that align with NHLBI’s mission and address unmet medical needs or significant scientific opportunity.

15. Goals Goal 3 Incubate our most promising technologies in accordance with industry requirements to facilitate their translation to commercial products that improve patient care and enhance health.

16. Goals Goal 4 Create a high-performing, sustainable infrastructure that will serve as a model to academic research centers.

17. Governance Center Director Associate Director Domain/ Site Leaders Cardiovascular TherapeuticsDevices Lung & Sleep Disorders Blood Diseases Diagnostics Domain Areas Projects Program Resources Administrative & Budgetary Support Website & Data Management Industry Relations & IP CTSA Infrastructure Evaluation & Tracking Project Management External Selection Committee Business Review Panel Skills Development Program External Advisory Board Executive Committee

18. External Selection Committee No fewer than 5 members Size and composition depends on RFAs under review Appointed by Executive Committee May be present and former faculty and/or industry leaders Must be external to institution(s)

19. External Advisory Board Consists of no fewer than 5 members Experienced business leaders Includes NHLBI Program Officer Advice about operations, project development Catherine Mackey, PhD Former Senior VP, Pfizer Founder, MindPiece Partners Francis Duhay, MD VP Medical Affairs and CMD, Edwards Lifesciences Lawrence Souza, PhD Former Senior VP, Amgen Founder, Coastview Capital,

20. Business Review Panel Five members VCR on each campus appoints one member Evaluate Center’s progress toward sustainability Bill Ouchi, PhD UCLA Initial Chair Anderson School

21. CAI Administration Administration is based at UCLA –Anne Skinner is Administrative Director UCLA CTSI maintains CAI website –CAI information, RFP, project-tracking –Doug Bell, MD, PhD leads UCLA CTSI conducts evaluation with UC BRAID –Pamela Davidson, PhD, MSHS leads

22. Governance Tasks for First 100 Days Executive Committee names at least 5 members to the External Selection Committee VCRs at UCD, UCSD, UCI, UCSF each name 1 faculty to Business Review Panel Name at least 2 members to External Advisory Board.

23. Governance Tasks for First 100 Days 1 meeting: Executive Committee, Center Director, Associate Director & External Advisory Board 3 meetings (1 per month): Center Director, Associate Director & Executive Committee 3 meetings (1 per month): Center Director, Domain and Skills Development Leaders

24. Administrative Tasks for First 100 Days Initiate intercampus sub-awards Identify campus administrative leads Build website Begin coordination/communication process

25. Discussion Process for naming External Advisory Board members Do we want more than 5 EAB members? Deadlines for naming members to EAB, Business Advisory Panel, and External Selection Committee

26. Technology Selection Overview 5-Step Process Solicit 2-page pre-applications 1 st Review: Review Panels assembled by Domain Leaders review pre-applications and invite full applications 2 nd Review (Leadership Review): Executive Committee, Center Director, Assoc. Director, Domain Leaders and ad hoc reviewers select full proposals 3 rd Review (External Review): External Selection Committee scores proposals and sends to NHLBI 4 th Review: NHLBI makes final selection

27. Technology Selection Overview Pre-application Review RFP Pre-application Full Application External Selection Committee Review NHLBI Review Leadership Review Technologies Selected for Entrance to Center

28. Technology Selection Timeline Solicitations occur three times a year, one for each platform (therapeutics, devices, diagnostics) RFPs for the platforms run concurrently Time from solicitation to prioritization by External Selection Committee takes 7 mos. Up to 3 technologies enter Center in yr.-1 Awards of up to $200K Solicit Pre- Application Review Pre- Application 1 month Develop and Submit Full Application First Review of Full Application ESC Review of Application 1 month 3 months

29. Pre-application and Review Pre-application Review RFP Pre-application Full Application External Selection Committee Review NHLBI Review Leadership Review Technologies Selected for Entrance to Center

30. Eligibility Faculty in all series and ranks at UC Davis, UC Irvine, UCLA, UC San Diego, and UC San Francisco Postdoctoral scholars are eligible to submit applications as Co-PI with a faculty PI Projects with existing or imminent target validation and a clear clinical indication Patents or patent applications are filed or potential for obtaining defensible intellectual property is strong

31. Solicitation Process Broad solicitation Added focus on cardiology, pulmonary, hematology, cardiothoracic surgery, etc. Centralized RFP Webinar on submission process Campuses to provide potential applicants with referrals for help with business plans, grant writing, IP, licensing, team building Innovators may apply for Catalyst Grants from their campus CTSA to support team building

32. 2-page Pre-application Centralized online submission The two-page pre-application contains: –description of the invention –its potential market and impact –description of competitive landscape –whether pre-clinical or early clinical proof of concept is achieved or imminent –what is needed to make the invention licensable –proposed budget Review Panels (one for each platform technology) review pre-applications for scientific merit and commercial potential

33. Review Panels Selected by Domain Experts Includes external experts from industry and internal or external academic experts Domain Experts do not participate in pre- application review At least some Review Panel members should be expert in platform under review

34. Technology Solicitation Tasks for First 100 Days Develop RFP for 2-page pre-application Create Webinar about submission process Develop online submission “package” Each campus site develop plan for advertising RFP Recruit Review Panel members

35. Discussion Review criteria for pre-application Scoring for pre-application Local or central pre-application review? Size of review panel(s)? Begin with one platform or solicit all three at once? Are campuses prepared to provide guidance with IP, licensing, etc.? Date for RFP release

36. Technology Selection: Full Application Pre-application Review RFP Pre-application Full Application External Selection Committee Review NHLBI Review Leadership Review Technologies Selected for Entrance to Center

37. Full Application By invitation Central RFP submission Full-proposal format: –Summary, including objectives –Background, including research strategy –Product development & commercialization –Strategic partnerships –Budget 3 months to submit

38. Full Application Review Criteria –Unmet medical need –Development feasibility –Commercial attractiveness –Intellectual property status –Relevance to NHLBI mission –Metrics for success o Evidence of target validation (therapeutic) o Time and cost of prototyping (device) o Combination of the above (diagnostic)

39. Full Application: Leadership Review Reviewers –Executive Committee –Center Director and Assoc. Director –Domain Leaders for disease and platforms under review –As needed: Ad hoc reviewers from academia, industry, venture capital with specific expertise in the diseases and platforms under review. 1 month to conduct Leadership Review

40. Full Application: External Selection Committee Prioritize applications received from Leadership Review Same review criteria as Leadership Review 1 month to review Submit recommendations to NHLBI Reviewers –No fewer than 5 members; present and former faculty and/or industry leaders –Must be external to institution(s)

41. Full Application: Tasks for First 100 Days Develop RFP for full applications Develop online submission “package” for full application Begin to identify ad hoc reviewers for Leadership Review

42. Discussion Limit the number of applicants who are invited to submit full proposals? How many pages for full proposal? Include NIH review criteria? Scoring system?

43. Technology Selection: Second Chances Pre-application Review RFP Pre-application Full Application External Selection Committee Review NHLBI Review Leadership Review Technologies Selected for Entrance to Center Referral Consultation Award

44. Consultation Awards Eligibility –Proposal not selected for Center –Leadership Review or External Review recommends Consultation Award consideration Funded by campus CTSAs Amount and duration of awards vary –Most awards for 3-6 months Recipients must agree to resubmit and target a specific RFP for resubmission

45. Consultation Awards Consultation Awards will address gaps in following areas: –In vivo proof of principle –Hypothesis testing –IP assessment –Target product profile discussion –Regulatory assessment –Further development planning Skills Development Program will match awardees with mentors and expertise

46. Consultation Awards: Tasks for First 100 Days Each CTSA determines feasibility of offering Consultation Awards Skills Development Program begins to identify expertise in the following: –In vivo proof of principle –Hypothesis testing –IP assessment –Target product profile discussion –Regulatory assessment –Further development planning

47. Discussion Mechanics of Consultation Award –Application process or automatic review based on referral? –Standard or local criteria? –Timeframe for review? –Who conducts review? Size of Consultation Award –Set an upper limit or local decision? Resubmission Process –Pre-application or directly to full review?

48. Technology Development Process Technology Enters Center Project Design Project Plan Licensing Product Development Exit Center Project Management Team Project Design Team

49. Technology Development Two phases – Project design – Project management Collaboration with campus IP office during entire development process is critical Simultaneous skills development –We develop the innovation and the innovator

50. Project Design Center Director names Project Design Team –Platform expert(s) –Disease expert(s) –Campus Technology Transfer Officer –Project manager –Innovator Two months to develop project plan Must be approved by Center Director

51. Elements of Project Plan Product profile and exit strategy Task definition Resource identification Identification of critical path and milestones Gantt charts for –task responsibility and ordering –time to task completion –activity-based budgets –process for tracking project against milestones –process for periodic review

52. Product Profile Example Device Development Profile Unmet Clinical Needs Technology / Components Cost Breakout Good Laboratory Practices Testing / Validation Hardware / Software Validation Animal Model Pilot Human Study IP/FDA Intellectual Property FDA Device Class Approval Path Commercial Partner / FDA

53. Gantt Chart Q1Q2Q3Q4Year 2 Procedure JanFebMarAprMayJunJulyAugSeptOctNovDec Quality Control/Records Components/Assembly Testing/Validation Animal model Evaluation-decision Pilot study-human trial Commercial partner FDA

54. Project Management Site leader assembles team to manage product development Team includes at a minimum: –Site leader –Project manager –Innovator –Campus Technology Transfer Officer –Mentors assigned to innovator by Skills Development Program Team may also include ad hoc disease, platform or business experts assigned by Site leader Project managers report to Site leaders

55. Monitoring Progress Continually assess progress against milestones Terminate projects that do not make adequate progress Use risk-mitigation strategies to permit multiple paths to success Center Director is final authority for go/ no-go decisions

56. Go/No-Go Decisions Potent, Selective Compounds Test PK Properties All Compounds Intraperitoneal In Vivo Assays Sufficient Therapeutic Index Go Insufficient Therapeutic Index No Sufficient t ½ and oral bioavailability Oral In Vivo Assays Sufficient Therapeutic Index Go Insufficient Therapeutic Index No

57. Exit Strategies Continued evaluation by Center leadership Licensing Review by Technology Transfer Office High future interest Further incubation or marketing Development at the Center Exit Processes Development Outside the Center Project aborted by PI Further management by Technology Transfer Office Licensing not achieved Low future interest Return IP

58. Technology Development: Tasks for First100 Days UCLA and UCSF identify possible project managers Each campus begins to identify internal and external disease, platform and business experts for project design and project management teams Site leaders liaise with campus Technology Transfer Office Establish committee of Technology Transfer Officers from each campus to advise the Center. Campuses identify cores that will be available to CAI innovators

59. Technology Development Discussion How do we make unique cores on each of our campuses visible to innovators at all campuses? –Can CTSA Translational Technologies and Resources Programs coordinate this effort? What must be done to make cores available to all innovators with minimal red tape? Process for organizing committee of Technology Transfer Officers from each campus

60. Skills Development