Advancing Biotechnology Innovation Ming Zhao, PhD NCI SBIR Development Center June 24, 2014

Discovery and development of therapeutics and diagnostics 2 Target Identification Chemical Synthesis, HTS Screening & Lead Selection Preclinical testing & Lead Optimization Clinical Trials I, II & III FDA Filing, Approval & Lunch Therapeutic Agents Post- Marketing & Drug Surveillance $800 Million/14 years$3.4 Billion/Year Diagnostic Opportunity Identification Chemical Synthesis, Lead Selection & in vitro Assays Preclinical testing & Lead Optimization Clinical Trials I, II & III FDA Filing, Approval & Lunch Diagnostic Imaging Agents Post- Marketing & Drug Surveillance $150 Million/10 years$400 Million/Year

S-S 11  22  extracellular intracellular Adapted from Gurnett, CA et al, Neuron 16, Ca ++ H2NH2NCO 2 H  2  as drug targets  2   2  Gabapentin Voltage-gated Calcium Channels

Drug Development Process 4 TARGET IDENTIFICATION The physiological, cellular, and/or genetic basis of a disease is studied to identify potential therapeutic targets

Pregabalin is marketed by Pfizer under the trade name Lyrica. It was designed as a more potent successor to gabapentin. Pregabalin received U.S. FDA approval for use in treating epilepsy, diabetic neuropathic pain, and postherpetic neuralgia in December 2004 and appeared on the U.S. market in fall It is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures It is also effective for generalized anxiety disorder and is approved for this use in the European Union and Russia Sales reached $3.063 billion in Lyrica is one of four drugs which a subsidiary of Pfizer in 2009 pleaded guilty to misbranding "with the intent to defraud or mislead". Pfizer agreed to pay $2.3 billion in settlement Pregabalin/Lyrica 5

Can We Have A Better Way in Drug Discovery? 6

Discovery and development of therapeutics and diagnostics 7 Target Identification Chemical Synthesis, HTS Screening & Lead Selection Preclinical testing & Lead Optimization Clinical Trials I, II & III FDA Filing, Approval & Lunch Therapeutic Agents Post- Marketing & Drug Surveillance $800 Million/14 years$3.4 Billion/Year Diagnostic Opportunity Identification Chemical Synthesis, Lead Selection & in vitro Assays Preclinical testing & Lead Optimization Clinical Trials I, II & III FDA Filing, Approval & Lunch Diagnostic Imaging Agents Post- Marketing & Drug Surveillance $150 Million/10 years$400 Million/Year

Molecular Imaging Technology

Molecular Imaging – Platform Technology Streptavidin (or avidin) & biotin Bispecific antibody and hapten DNA and complementary DNA PNA and complementary PNA Morpholino and complementary morpholino FKBP and rapamycin The effector molecule is given some time after the targeting agent. This allows time for the targeting agent to localize in tumor lesions and, more importantly clear from the body. Tumor target cPNA (effector) Ab PNA

Funding for Early Stage Ventures from NCI

11 J. Robert Beck Lincoln – Fox Chase CC

Total CNPC personnel: 400+CNPC Dollars: - $116M

NCI SBIR&STTR: Advancing the Commercialization of New Cancer Innovations

Congressionally-Mandated Programs 2.8% 0.4% Set Aside (FY14) ~$700M annually at NIH ~$119M annually at NCI 14  Small Business Innovation Research (SBIR) Set-aside program for small business concerns to engage in Federal R&D with the potential for commercialization Federal agencies with an extramural R&D budget > $100M  Small Business Technology Transfer (STTR) Set-aside program to facilitate cooperative R&D between small business concerns and U.S. research institutions with the potential for commercialization Federal agencies with an extramural R&D budget > $1B

Phase III COMMERCIALIZATION Phase II DEVELOPMENT Phase I FEASIBILITY Research & Development Commercialization plan required $1.5 million over 2 years Commercialization stage Use of non-SBIR/STTR funds Fast Track Application Combined Phase I & II Fast Track Application Combined Phase I & II SBIR & STTR: Three-Phase Program Hard caps on award sizes: $225,000 for Phase I; $1.5 million for Phase II Certain awards may exceed these caps if covered by topic-specific waivers Actual funding may vary by topic Proof-of-Concept study $225,000 over 6 months (SBIR) or 1 year (STTR) Direct to Phase II Skip Phase I 15

NCI SBIR Phase IIB Bridge Award CROSSING THE VALLEY OF DEATH Phase III COMMERCIALIZATION Phase II DEVELOPMENT Phase I FEASIBILITY NCI SBIR Phase IIB Bridge Award Provides up to $1M per year for up to 3 years Open to any NIH-funded Phase II awardees with projects relevant to NCI mission Accelerates commercialization by incentivizing partnerships with third-party investors & strategic partners earlier in the development process Competitive preference and funding priority to applicants that can raise substantial third-party funds (i.e., ≥ 1:1 match)

 SBIR & STTR Omnibus Solicitations for Grant Applications Release: January Receipt Dates: April 5, August 5, and December 5  See the NIH Guide for other Program Announcements (PA’s) and Requests for Application (RFA’s), i.e. grants Release: Weekly Receipt Dates: Various  Solicitation of the NIH & CDC for SBIR Contract Proposals Release: August – sign up for the list to get notified! Receipt Date: Early November Multiple Funding Solicitations Know the Application Deadlines

Topic 326: Development of Novel Therapeutic Agents That Target Cancer Stem Cells 18 (Fast-Track proposals will not be accepted.) Budget (total costs): PhI: $225,000 for 9 months; PhII: $1,500,000 for 2 years Number of anticipated awards: 3-5 Project Goals: Proposals under this topic should be involved the development of novel therapeutic agents that target CSCs. These small molecules or biologics should be designed to target CSCs, CSC-related biomarkers, or CSC pathways that affect fundamental processes associated with carcinogenesis, tumor progression, maintenance, recurrence or metastasis. Particular emphasis is placed on agents that target CSC self-renewal, regeneration, or differentiation processes. Phase I Activities & Deliverables: Demonstrate in vitro efficacy for the agent(s) that targets CSCs. Validate the effect of the agent(s) on CSCs. The offerors are required to provide evidence confirming that the agent(s) specifically targets CSCs (e.g., measurement showing reduced quantity, viability, or frequency of CSCs). Conduct structure-activity relationship (SAR) studies, medicinal chemistry, and/or lead antibody optimization (as appropriate). Perform animal toxicology and pharmacology studies as appropriate for the agent(s) selected for development. Develop a detailed experimental plan (to be pursued under a future SBIR Phase II award) necessary for filing an IND or an exploratory IND.

SBIR/STTR Portfolio Health IT

NCI SBIR Development Center Phone: Follow us on Ming Zhao, PhD Program Director