●Drug ●Device ●Discovery ●Development

a critical new initiative… building on success

BRAI 4

“It appears that many — perhaps most — new therapeutic uses of drugs have been discovered by motivated and observant clinicians working with patients in the real world.”

Scannell et al. Nature Reviews: Drug Discovery 11:191, 2012

D4 at UC GOALS and OBJECTIVES The overall goal of BRAID D4 is to leverage existing shared resources across the UC system with the uniquely creative and innovative basic and clinical research at individual campuses in order to enable individual research and create value in the broad field of drug and device discovery.

Why D4?

Despite dramatic advances… translation of basic biomedical research into safe and effective clinical applications remains a slow, expensive, and failure-prone endeavor. …[We must] catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of diseases and conditions.

D4 and the “Valley of Death

D4 and the “Valley of Death

University Hospitals touts new $250M drug

development model

The Cleveland-area health system has launched a new $250 million project that it’s touting as something that could become a national model for developing promising drugs and bringing them to market. The aim of the new Harrington Project for Discovery & Development is to advance drug candidates through the period that runs from late animal testing to mid-clinical development in which companies find it difficult to attract funding to keep the drug development process going.

Around the Nation--D4 in progress

D4 at UC

Planning began over a year ago

ACCOMPLISHMENTS to DATE

•Identified leaders at each campus

•Developed an action plan with specific deliverables

•Proposed modest and achievable costs to our recent UCOP request

D4 at UC

D4 at UC

IDEAS DISCUSSED TODAY IN LIGHT OF THE UCOP BRAID INITIATIVE-1

CONSENSUS (Role of D4 in BRAID) • D4 is an essential component of BRAID that

complements and supports BRAID’s current mission

• D4 successes will mutually benefit the contracting and IRB metrics established by UCOP in it current funding opportunity

• D4 can become a key component in BRAID’s MRU application in 2 years

IDEAS DISCUSSED TODAY IN LIGHT OF THE UCOP BRAID INITIATIVE-2

CONSENSUS (Role of D4 in Defining Key Themes) • Role of academia in D4

• Creating “value” in the process of drug and device discovery (not just $)

• D4 is a major link between NCATS and BRAID!

IDEAS DISCUSSED TODAY IN LIGHT OF THE UCOP BRAID INITIATIVE-3

CONSENSUS (Role of D4 UC-Wide) • Identify campus specific resources

• Match these resources with individual investigators

• Build teams in which unique drug and device discovery team requirements are addressed

• PatientNursesPhysicianBasic and applied scientists

IDEAS DISCUSSED TODAY IN LIGHT OF THE UCOP BRAID INITIATIVE-4

CONSENSUS (Role of D4 UC-Wide) • Addressing the knowledge/training gap

• Configuring and growing the academia-industry interaction

• Introduce industry-type “project management” paradigms into academic discovery processes

IDEAS DISCUSSED TODAY IN LIGHT OF THE UCOP BRAID INITIATIVE-5

CONSENSUS (Next Steps) • Strategic Planning Meeting*

• Solidify goals and aims

• Create D4 governance and infrastructure

• Identify metrics of success

• U54 Center of Accelerated Innovation (NHLBI)

Existing D4 Resources at UCSD

• Creation of Drug Discovery Institute

• High throughput screening with Sanford-Burnham

• Pre-clinical toxicology service

• Express licensing option for start-ups

• Drug discovery consultation service

• Unique libraries (marine products)

Existing D4 Resources at UC Irvine

The Science of Team Science

Existing D4 Resources at UCSF

Existing D4 Resources at UCLA

Fully Automated High Throughput Screening for Drug Discovery Expert technical staff support assay development, HTS execution, and hit validation • Small molecule libraries totaling 200,000 compounds, including FDA-

approved drugs, natural products, and novel/diverse compounds. • Functional genomics libraries for target identification/validation

• Genome-wide siRNA for mouse and human • Genome-wide shRNA for human in lentiviral vector • Genome-wide mammalian cDNA expression library

1. SAIC : synthesis

2. UC Davis : Formulation in cGMP facility

3. UC Davis CTCS: IND filing

4. UC Davis CTCS: monitoring and QA services

5. UC Davis CTSC: REDCap database

6. ?: preclinical reproductive tox

Existing D4 Resources at UC Davis

Development of Injectable Allopregnanolone for Treatment of Traumatic Brain Injury (Dr. Michael Rogawski)

Existing D4 Resources at UC Davis

1. Third Party Manufacturing and sterilization validation

2. UC Davis: large animal surgery facility (sheep)

3. UC Davis CTCS: IDE filing

4. UC Davis CTCS: monitoring and QA services

5. UC Davis CTSC: REDCap database

Development Of Esophageal Expansion Device For Improvement Of Swallow (Dr. Peter Belafsky)

Support D4 at UC

Helping all of our campuses contribute to the new national vision of team science and collaboration

Speeding thru the “Valley of Death”