Wednesday, September 15 10:00am-Noon

1. Business of Bio SeriesBringing Science to the Market: The National Cancer Institute SBIR & STTR Program Wednesday, September 1510:00am-Noon

2. Business of Bio SeriesWelcomeJim HughesVice President, Office of Research & Development University of Maryland

3. Business of Bio Opening RemarksDr. Curt CivinFounding Director, Center for Stem Cell Biology & Regenerative MedicineUniversity of MarylandSchool of Medicine

4. Business of Bio PresentationMichael WeingartenDirector,National Cancer InstituteSBIR Development Center

5. PresentationDr. Ali AndalibiProgram Director & Branch Chief, National Cancer InstituteSBIR Program

6. Bringing Science to the Market: The NCI SBIR Program University of Maryland BioPark September 15, 2010 Michael Weingarten Director, NCI SBIR Development Center

7. Today’s Presentation Program overview Strategic move to targeted solicitations Helping Companies Bridge the “Valley of Death” SBIR Phase II Bridge Award A New Approach to Managing SBIR NCI Investor Forum Regulatory Assistance Program 7

8. Congressional Goals • Stimulate technological innovation • Use small business to meet Federal R&D needs • Increase private-sector commercialization innovations derived from Federal R&D • Foster participation by minority and disadvantaged persons in technological innovation Small Business Innovation Development Act of 1982 Small Business Technology Transfer Act of 1992 8

9. Percent of NCI and NIH Budget Set Aside • SBIR: Set-aside program for small business concerns to engage in Federal R&D with the potential for commercialization • STTR: Set-aside program to facilitate cooperative R&D between small business concerns and U.S. research institutions with potential for commercialization 2.5% 0.3% ~$110 million annually at the NCI ~$650 million annuallyat the NIH 9

10. Reasons to Seek SBIR & STTR Funding • One of the largest sources of early stage of life sciences funding in the country. • A stable and predictable source of funding • Intellectual property rights are retained by the small business concern • Not a loan – no repayment is required • Doesn’t impact stock or shares in any way (no dilution of capital) • Provides recognition, verification and visibility • Can be a leveraging tool to attract other funding (VC, etc.)

11. SBIR Eligibility • Applicant must be a Small Business Concern (SBC) • Organized for-profit U.S. business • 500 or fewer employees, including affiliates • PD/PI’s primary employment (i.e., >50%) must be with SBC at the time of award and for duration of the project period • At least 51% U.S.- owned by individuals and independently operated • OR At least 51% owned and controlled by another (one) business concern that is at least 51% owned and controlled by one or more individuals 11

12. STTR Eligibility • Applicant is a Small Business Concern • Formal Cooperative R&D Effort • Minimum 40% by small business • Minimum 30% by U.S. research institution • U.S. Research Institution: College or University; Non-profit research organization; Federally-Funded R&D Center (FFRDC) • Intellectual Property Agreement • Allocation SBC of IP rights (to SBC) and rights to carry out follow-on R&D and commercialization • Principal Investigator’sprimary employment may be with either the Small Business Concern or the research institution 12

13. Multiple Funding Solicitations • NIH SBIR/STTR Omnibus Solicitations for Grant Applications • Release: January • Receipt Dates: April 5, August 5, and December 5 • Solicitation of the NIH & CDC for SBIR Contract Proposals • Release: August • Receipt Date: Early November • See NIH Guide for various other Program Announcements (PAs) and Requests for Application (RFAs), i.e. other grants Release: Weekly Receipt Dates:Various 13

14. NCI Has Moved to More Targeted Funding Opportunities • Goal is to improve success in commercialization by focusing on more directed research. • Invest in the technology priorities of NCI that also have greatest potential for commercialization • Catalyze targeted technology development and draw private sector investment in specific areas • Approximately 20% of NCI’s SBIR budget is now invested in contracts. Approximately $11M in new contract funding opportunities just announced.

15. SBIR Portfolio Summary (Active as of July 1 2010)Grants & Contracts -- $110M budget

16. http://sbir.cancer.gov 16

17. NCI SBIR Phase II Bridge Award 17

18. SBIR & STTR: Three-Phase Program PHASE I – R41, R43 Feasibility Study $150K and 6-month (SBIR) * or 12-month (STTR) Award Phase II Bridge Award • PHASE II – R42, R44 • Full Research/R&D • $1 million and 2-year Award (SBIR & STTR) * • Commercialization plan required • PHASE III • Commercialization Stage • Use of non-SBIR/STTR Funds 18 * Note: Actual funding levels may differ by topic.

19. Follow-on to SBIR Phase II Helps early-stage companies cross the “Valley of Death” by: Facilitating partnerships with third-party investors & strategic partners Incentivizing third-party investments earlier in the development process NCI is sharing in the investment risk with other investors Incentive Structure Gives competitive preference and funding priority to applicants that can raise third-party funds (i.e., 1:1 match) Affords NIH the opportunity to leverage millions in external resources Provides valuable input from third-party investors in several ways: Rigorous commercialization due diligence prior to award Commercialization guidance during the award Additional financing beyond the Bridge Award project period SBIR Phase II Bridge Award 19

20. Example: How the Bridge Award Would Apply in the Area of Drug Development Phase I & Phase II SBIR Preclinical Development (Lead Development, Animal Studies, File IND) Target Identification & Validation Safety Review Clinical Trials NDA Review Commercialization SBIR Bridge Award Private Investment SBIR Bridge Award addresses the problem by bridging the “Valley of Death” SBIR Bridge Awardallows NIH to share investment risk by incentivizing investors or strategic partners to evaluate projects and commit funds much earlier 20

21. Example: How the Bridge Award Would Apply in the Area of Drug Development Phase I & Phase II SBIR SBIR Bridge Award STOP STOP 2nd Year 1/3 of funds 1st Year 1/3 of funds 3rd Year 1/3 of funds YES YES • Milestones reached? • Matching Funds? • Milestones reached? • Matching Funds? • Milestones reached? • Matching Funds? NO NO Preclinical Development (Lead Development, Animal Studies, File IND) Target Identification & Validation Safety Review Clinical Trials NDA Review Commercialization SBIR Bridge Award Private Investment 21

22. Six Bridge Awards in FY2009 22

23. Third-party InvestmentCumulative for 6 Bridge Awards Made in FY2009 23

24. New Approach for Managing SBIR at NCI 24

25. SBIR Development Center Old SBIR Management Model at NCI • Awards were managed by 40-50 people who each spent a small amount of their time on SBIR • Few of these NCI program directors had significant industry experience or commercialization expertise New Development Center at NCI • Team of 9 program directors and one center director • Exclusively focused on management & administration of NCI’s SBIR/STTR portfolio • Center staffed by program directors with both industry experience and scientific expertise so they can mentor companies on strategy. • Center staff interacts actively with NCI program staff. This includes assigned division liaisons. 25

26. SBIR Development Center Staff • Ali Andalibi,PhD(Branch Chief) • Previous • NSF – SBIR Program Director, Medical Biotechnology • House Ear Institute – Scientist & Director, New Technology and Project Development • Trega Biosciences, Inc. – Research Scientist • Michael Weingarten,MA(Director) • Previous • NASA – Program Manager, NASA Technology Commercialization Program • Greg Evans,PhD(Branch Chief) • Previous • NHLBI/NIH – Program Director, Translational and Multicenter Clinical Research in Hemoglobinopathies • NHGRI/NIH – Senior Staff Fellow • Natalia Kruchinin, PhD(Program Director) • Previous • QIAGEN, Inc. – Molecular Diagnostics Applications Manager • Motorola, Inc. – Senior Scientist, Gene Expression Assays • Patti Weber, DrPH(Program Director) • Previous • International Heart Institute of Montana –Tissue Engineering and Surgical Research • Ribi ImmunoChem Research, Inc. – Team Leader, Cardiovascular Pharmacology • Andrew J. Kurtz,PhD(Program Director) • Previous • NIH – AAAS Science & Technology Policy Fellow • Cedra Corporation – Research Associate, Bio-Analytical Assays and Pharmacokinetics Analysis • Jian Lou, PhD(Program Director) • Previous • Johnson & Johnson – Research Scientist, Target Validation & Biomarker Development • Lumicyte, Inc. – Director, Molecular Biology Systems Analysis • David Beylin,MS(Program Director) • Previous • X/Seed Capital Management, LLC, Consultant • Naviscan PET Systems, Inc., Vice President, Research • Todd Haim, PhD(Program Analyst / AAAS Fellow) • Previous • National Academy of Sciences – Christine Mirzayan Science and Technology Policy Fellow • Pfizer Research Laboratories – Postdoctoral Fellow, Cardiac Pathogenesis & Metabolic Disorders • Deepa Narayanan, MS(Program Director) • Previous • Naviscan PET Systems, Inc., Director, Clinical Data Management (Oncology Imaging & Clinical Trials) • Fox Chase Cancer Center, Scientific Associate (Molecular Imaging Lab)

27. New Activities of Center Active outreach to bring in a new class of commercially viable applicants Coaching companies on developing stronger applications Active management of projects and better oversight Mentor and guide companies throughout the award period When appropriate, matchmaking with investors

28. 2010 NCI SBIR Investor Forum hosted by San Jose BioCenter • 2010 Investor Forum: November 9, Stanford , CA • http://sbir.cancer.gov/investorforum/ • Featured Small Businesses • Exclusive opportunity for ~ 15 NCI awardees to showcase their companies to investors • Present to and network with the top investors & strategic partners in the country • Participate in panel discussion with successful Bridge awardees and their investors • Investors • Opportunity to evaluate NCI’s top companies • Exclusive one-on-one meetings "The Forum was a great opportunity to get exposed to new companies in oncology." - Ankit Mahadevia, M.D., MBA, Life Sciences Associate, Atlas Venture "I was very impressed with your choice of companies.The mix of stages was ideal." - Sarah Bodary, Ph.D., Venture Partner, SV Life Sciences 28

29. 2009 NCI SBIR Investor Forum Outcomes One company raised $30M to fund clinical trials of a new generation of oral antifolates One company developed relationships with big pharma that led to the launch of a new drug screening service they are offering. One company developed relationships with a VC that is going to lead their next round of venture financing. Several other companies are going thru due diligence.

30. Regulatory Assistance Goal Provide Phase II awardees access to regulatory consultants to accelerate the FDA approval process for drugs, biologics and devices Path Provide appropriate Phase II awardees ≥30 hours of consulting time and activities, including: A preliminary conversation with the company regarding the writing of a regulatory plan Review and editing of the regulatory plan Post review discussion 30

31. http://sbir.cancer.gov Michael Weingarten Director SBIR Development Center Phone: 301-594-7709 weingartenm@mail.nih.gov

32. The NCI SBIR ProgramApplications Ali Andalibi, PhD Program Director, NCI SBIR Development Center September 15, 2010

33. 2010 NCI SBIR Contract Funding Opportunities

34. Contracts vs. Grants What's the difference? • Grant applications in any area within the mission of the awarding components identified in the SBIR/STTR Omnibus Grant Solicitations • Contract proposals are accepted only if they respond specifically to a research topic within the Contract Solicitation • Contract topics are much more targeted, narrowly focused • 3 receipt dates per year for company-initiated SBIR/STTR Grant Applications (Phase I or Phase II) submitted under Omnibus • Only 1 receipt date per year for NCI SBIR Contract Proposals All grant applications and contract proposals MUST be received in response to a published NIH funding opportunity announcement (FOA)

35. NIH Issues Multiple SBIR Solicitations • SBIR/STTR Omnibus Grant Solicitation • Release:January • Receipt Dates:April 5, August 5, and December 5 • SBIR Contract Solicitation (NIH, CDC) • Release:EarlyAugust 2010 • Receipt Date:Early November 2010 NIH Guide for Grants and Contracts Release:Weekly Receipt Dates:Various For more information visit: http://sbir.cancer.gov

36. NCI SBIR Contract Funding Opportunities • Development of Anticancer Agents • Companion Diagnostics: Predictive and Prognostic Tests Enabling Personalized Medicine in Cancer Therapy Innovative • Development of a Molecular Diagnostic Assay to Detect Basal-like Breast Cancer • Alternative Biospecimen Stabilization and Storage Solutions • Radioprotector/Mitigator Development to Decrease Normal Tissue Injury During Radiotherapy • Development of Molecular Pharmacodynamic Assays for Targeted Therapies • Development of Devices for Point of Care Analysis of Circulating Tumor Cells Development of Glycosylation-Specific Research Reagents (Antibodies and Aptamers) • Algorithms for Automated Quantitative Imaging of Tumor Microenvironment

37. NCI SBIR Contract Funding Opportunities • Systems for Automated Storage, Analysis, and Reporting of Objective Behavioral Exposures • Methods and Tools for Quantitatively Measuring Non-Coding RNAs in Cancer Early Detection, Prediction, and Diagnosis • Low-Field Electron Paramagnetic Resonance Imaging Device to Optimize Development of Anti-Angiogenic Therapeutics in Cancer Animal Models (NIH TT) • A New Type of Vaccine for Prevention of HIV Infection and HIV-Associated Cancers (NIH TT) • Therapeutics and Theranostics Based on Nanotechnology • Nanotechnology Sensing Platforms for Improved Diagnosis of Cancer • Development of Clinical Automated Multiplex Affinity Capture Technology for Detecting Low Abundance Cancer-related Proteins/Peptides • Development of Quantitative Multiple Reaction Monitoring Mass Spectrometry Assays for the Detection of Cancer Related Aberrant Proteins/Peptides

38. NCI SBIR Contract Funding Opportunities • Systems for Automated Storage, Analysis, and Reporting of Objective Behavioral Exposures • Development of Blood-based Methods for the Detection of Cancer Recurrence in Post-Therapy Breast Cancer Patients • Novel Digital X-ray Sources for Cancer Imaging Applications • Development of Innovative Algorithms/Software for Processing & Analysis of In Vivo Images in Oncology • Novel Imaging Agents to Expand the Clinical Toolkit for Cancer Diagnosis, Staging, and Treatment

39. Development of Anticancer Agents • Budget: $200,000 for Phase I; $1,500,000 for Phase II • Number of Anticipated Awards: 5 • Receipt Date: November 8, 2010 • Project Goal and Major Focus: • To support critical pre-IND research for small companies developing candidate therapeutic agents of interest. • Work scope may include animal efficacy testing, structure activity relationships (SAR), medicinal chemistry, formulation, production of GMP bulk drug and clinical product, as well as pharmacokinetic, pharmacodynamic, and toxicological studies.

40. Development of Devices for Point of Care Analysis of Circulating Tumor Cells • Budget: $200,000 for Phase I; $1,000,000 for Phase II; FT Accepted • Number of Anticipated Awards: 4 • Project Goal and Major Focus: • The short term goal is to demonstrate the technical viability of the proposed approach to detect, isolate, or eliminate CTCs in an experimental setting. • The long term goal is to develop Point of Care (POC) devices and methods of circulating tumor cell (CTC) detection, enumeration, isolation, removal and subsequent genetic and proteomic analysis for better cancer diagnosis, prognosis and treatment. • The major focus is to develop clinical tools rather than tools for basic research.

41. A New Type of Vaccine for Prevention of HIV Infection and HIV-Associated Cancers (SBIR Technology Transfer) • Budget: $300,000 for Phase I; $2,500,000 for Phase II • Number of Anticipated Awards: 1 • Project Goal and Major Focus: • This is an SBIR Technology Transfer topic, whereby intramural inventions are licensed to qualified small businesses with the intent that those businesses develop these inventions into commercial products that benefit the public. • The ultimate goal of this NCI SBIR project is to accelerate the development of efficacious vaccines that can activate broadly neutralizing anti-HIV-1 antibody (bnAb) precursor germline B-cells and elicit anti-HIV-1 bnAbs. • The short term goals of this topic are to test the in vivo immunogenic potential of the identified potential primary HIV immunogen in an innovative animal model and identify one or more candidate primary immunogens.

42. Submitting an Application

43. Keys to a Strong Application • Significant, innovative, and focused science • Significant product and/or commercial potential • A product-focused application is more likely to have support of business reviewers • A project with sound financial projections is more likely to attract a partner • Translational research/clinical applications projects should involve the appropriate collaborators • Physicians • Microbiologists • Statisticians

44. Know NIH Review Criteria • Does the study address an important problem and have commercial potential? Significance • Are design and methods well-developed and appropriate? Are problem areas addressed? Approach • Are there novel concepts or approaches? Are the aims original and innovative? Innovation • Is the investigator appropriately trained and capable of managing the project? Investigator • Does the scientific environment contribute to the probability of success? Is the environment unique? Environment • Is the company’s business strategy one that has a high potential for success? Commercialization

45. Key #1Start Application Process Early • Start developing your application as early as possible. You need time to develop a strong proposal. • Seek help of experienced applicants early in process • Assemble a strong scientific team • If you have a weakness or gap in expertise, fill it early

46. Key #2Consider Your Company’s Strengths and Weaknesses • Consider your company’s strengths • Try to exploit those strengths to address a specific NIH Program initiative • Consider your weaknesses too • It is rare that a small company will have all the necessary expertise for a strong application • If you have no track record of commercialization, consider getting a partner who does • Partner with other companies or academics to fill gaps • Review similar, currently funded projects using NIH Research Portfolio Online Reporting Tools (http://report.nih.gov)

47. Key #3Always Consider the Reviewers • Who is going to review your application? • All members of the Review Panel will score your application • The primary reviewer, as well as the two or three others will have read your application and will be leading its discussion • Combination of academic and industry reviewers

48. Key #3Always Consider the Reviewers • What are they looking for? • Readable and understandable application • Do not assume they will know everything you know • You understand your application best so convey it to them • Clear and concise language, “lay summary” • Clear plan for Phase I, II and commercialization • Feasible methods • Appropriate objective tests of success for each Specific Aim • Promising preliminary data are very influential • Solid letters of support for commercialization

49. Key #3 Always Consider the Reviewers • Read your material critically as if you were the Reviewer • What are the weaknesses? • Point out potential difficulties, do not hide them • Suggest ways to address them or provide rationale • Recruit an independent reader • Provide alternative methods if a particular approach is not successful • Help the Reviewer write his/her critique

50. Key #3 Always Consider the Reviewers • Be realistic about your goals • Provide a feasible timetable for key objectives • Be realistic about your budget • Ask Program Director for early guidance