Advancing Biotechnology Innovation

http://sbir.cancer.gov

Ming Zhao, PhDNCI 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-SS

-S

1

2

extracellular

intracellular

Adapted from Gurnett, CA et al, 1996. Neuron 16, 431-440.

Ca++

H2N CO2H

a2d as drug targets

a2 1da2 2d

Gabapentin

Voltage-gated Calcium Channels

Drug Development Process

4

TARGETIDENTIFICATION

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 2005.

• 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 2010.

• 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 goal is to use PET to image tumor in vivo

PET imaging

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

Tumortarget

cPNA(effector)

Ab

PNA

Funding for Early Stage Ventures from NCI

11

J. Robert BeckLincoln – Fox Chase CC

Community Network Program Centers

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

NCI SBIR&STTR: Advancing the

Commercialization of New Cancer Innovations

http://sbir.cancer.gov

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 IIICOMMERCIALIZATION

Phase IIDEVELOPMENT

Phase IFEASIBILITY

• Research & Development• Commercialization plan

required• $1.5 million over 2 years

• Commercialization stage• Use of non-SBIR/STTR

funds

Fast Track ApplicationCombined 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 IIICOMMERCIALIZATION

Phase IIDEVELOPMENT

Phase IFEASIBILITY

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: JanuaryReceipt 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: WeeklyReceipt Dates: Various

Solicitation of the NIH & CDC for SBIR Contract Proposals

Release: August – sign up for the email list to get notified!Receipt Date: Early November

Multiple Funding SolicitationsKnow the Application Deadlines

http://grants.nih.gov/grants/guide

Topic 326: Development of Novel Therapeutic Agents That Target Cancer Stem Cells

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(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.

Therapeu-tics33%

Devices for Cancer

Therapy7%Imaging

20%

In Vitro Diagnos-

tics21%

Health IT7%

Cancer Control and Epidemiology

11%

TherapeuticsDevices for Cancer TherapyImaging In Vitro DiagnosticsCancer BiologyCancer Control and Epidemiology

SBIR/STTR Portfolio

Health IT

NCI SBIR Development CenterNCIsbir@mail.nih.gov Phone: 240.276.5300

http://sbir.cancer.gov

Follow us on Twitter @NCIsbir

Ming Zhao, PhDProgram Director

zhaoming3@mail.nih.gov