01- PRISTIQ Strategic and Tactical IE Presentation ppt

Report
On Campus Workshop – UCSD
September 25, 2012
Rick Lindberg, Site Head of CTI-California
What we will cover today…
What is CTI?
– How does the CTI partnership work?
– In what ways is CTI different than other programs on campus?
What kind of research is CTI interested in?
– Focus on Translational Research via biologic modality
– Successful characteristics and attributes of funded projects
– Case studies of successfully funded proposals
Next Steps for submitting a proposal to CTI
– Why choose to collaborate with CTI?
•Pfizer Confidential
2
Challenges to Pharmaceutical Industry and Academic Centers
Slow progression of pipeline
Cost of drug development
Cost of drug discovery
•Industry
Productivity
Pressure from:
Stakeholders investors
Payors Physicians
Legislators
Regulators
Patients
Focused on Translational Medicine PIs challenged to
translate discoveries
VC funding mechanism
to the clinic while
Academia
maintaining
Funding pressures
"control"
CTI
New partnership to deliver on the promise of innovative discoveries to
treat diseases of high unmet medical need with differentiated new
medicines
3
•Pfizer Confidential
Increasingly, major biomedical institutions and industry share
common objectives…
Basic research
Patient access
Applied research
Novel targets
Innovative drugs
Precision medicine
Patient impact
Therapeutic
Technologies
Enabling
Functions
Clinical material
•Pfizer Confidential
4
Centers for Therapeutic Innovation (CTI)
CTI VISION
Accelerate the translation of innovative discoveries from
bench to the clinic
CTI STRATEGY
Co-localize Pfizer R&D resources where breakthrough
science is happening and leverage complimentary expertise
CTI APPROACH
A new entrepreneurial partnership at Academic Medical
Centers focused on translational medicine
•Pfizer Confidential
5
Core Elements of the CTI Model
Differentiation of CTI vs. NIH, VC, Other Pharma
Enable Translational Medicine via accelerating innovative discoveries from
target to proof of mechanism
Focused on protein therapeutics (e.g mAb)
Understand patient heterogeneity and stratification
Equitable IP Rights
Broad publication rights
Co-location with technology, scientists, drug development expertise
Collaborative use of Pfizer’s proprietary drug discovery tools and technologies
Support for IND- & clinical-enabling functions (e.g., toxicology, regulatory, etc)
Success-based funding/financial incentives (milestone & royalty payments)
Role for CTI Partnership:
Establish Proof or Mechanism in the clinic with innovative new therapeutics to treat diseases of high
unmet medical need
•Pfizer Confidential
6
Centers for Therapeutic Innovation – CTI Network
CTI-Boston
CTI-New York
CTI-California
•Pfizer Confidential
7
CTI – California
CTI - San Francisco
Address: Mission Bay Campus
Occupancy for ~40 Scientists
6 funded programs
CTI - San Diego
Address: Pfizer La Jolla Campus
Occupancy for ~12 Scientists
2 funded programs
•Pfizer Confidential
8
Collaboration governance via Joint Steering Committee (JSC)
Semi-autonomous via Joint Steering Committee (JSC) governance
Processes
Equal CTI-AMC decision making member representation
Responsible for proposal selection and funded program progression
Gary Firestein, Jerry Olefsky, David Brenner,
Catriona Jamieson, Michael Jackson
Anthony Coyle, Rick Lindberg, Scott Glaser,
Charles Baum, Gary Woodnutt
•Pfizer Confidential
9
Steering committee governance
Shared
AMC
CTI’s Partnership and Governance Model
New targets and associated IP
Early clinical studies conducted at AMC
$100-$250k provided to PI’s
project budget per year
$2M
$12M
•Decision point
•Decision point
•Milestone payment
Pfizer
$8M for IND enabling
studies
Drug discovery tools and
expertise
Project execution and
leadership
PK/PD studies
Non-clinical safety
assessment
Regulatory Support
•Pfizer Confidential
$2M to enable PoM
clinical trial
Program support
including clinical
and translational
sciences
Go / No-go
decision to exercise
license option
10
CTI Project Plan
R&D Stages, Budgets & Milestones
•Initiation
•SG0
•Start Screening
•SG1
Lead
Identification
Exploratory
Validation of target
biology
Development of
primary/secondary
screening assay(s)
Primary selection and
screening of protein
or scFv phage
libraries
•1st Year
Pfizer
Matching
Investment:
•Leads Optimized
•SG3
Lead Optimization
Lead Development
•SDS
•12 months
•ESD
•5 months
•Academic
•Budget:
•Leads Identified
•SG2
•~$100-250,000
•$1 million
•LD
•8 months
Sequence-based
manufacturing
assessment & seq.
optimization
•Candidate Drug
•SG4
Pre-Clinical
Development
Scale-up and
manufacturing of
batch for clinical
studies
Exploratory toxicity
studies
GLP toxicity studies
•~$100-250,000
•$1 - $2 million
•FIH POM
•SG6
Clinical
Development
•PreClin
•14 months
In vitro, ex vivo, or in
vivo PK/PD studies of
leads in mechanistic
model
•2nd Year
•IND / CTA
•SG5
•3rd Year
Phase 1 POM study in
stratified patient
population
•4th Year
•~$100-250,000
•$6- $7 million
•TBD
•~$2 million
•Estimated Investment (per program) – assumes program continues all the way to Phase 1 clinical study;
•contingency coverage for post-doc salary if project terminated during discovery phase of the project
•Pfizer Confidential
11
Partnership Model Encourages Collaboration at all levels
•CTI
Protein Therapeutics
Antibody Engineering
IND Enabling Studies:
•PK analysis
•Safety/Tox studies
•Manufacturing
AMC
Proposal Writing
Project Strategy
Reagent Generation
In vitro characterization
Biomarker Development
Patient Selection Strategy
Joint Steering Committee
•Pfizer Confidential
Targets
In vivo studies
Clinical studies
12
IP and Publishing Rights
Licensing Option
– One year following achievement of the PoM, Pfizer has an
option to obtain exclusive license rights
Publication Rights
– Findings can be published via submitting materials to the JSC
30 days prior to publication for review to ensure that no
confidential or patentable information is disclosed
•Pfizer Confidential
13
What We Look for: Key Attributes of Successful Programs
Essentials
– Targetable with a biologic
• Primarily monoclonal antibodies, peptides, proteins
– Novel mechanism addressing unmet medical need
– Strong link of pathway to human disease
Differentiators
– Ability to streamline path to proof-of-mechanism in humans
– Translating basic biological research into the clinic
• Connection of basic scientific researcher & clinical investigator
• Clinical differentiation opportunity via patient stratification,
molecular signatures, genetic associations, biomarkers
•Pfizer Confidential
14
Target Discovery
What Makes a Good Target?
Compelling validation of target/pathway
Target identification often comes from an association of target with
disease (e.g. expression pattern) and validation is the process of
defining the functional consequence (e.g. siRNA KD, KO mouse)
Considerations for defining an attractive target
– Link of mechanism to disease
– Target validation/biological evidence
• Evidence of translation to human disease
– Potential safety liabilities associated with target modulation
– Technical feasibility (e.g. druggability)
15
•Pfizer Confidential
Proposal Evaluation Criteria
Link of mechanism to disease
Target Validation/Biological Evidence
•
Evidence of Translation to Human Disease
Technical Feasibility (e.g. druggability with a protein therapeutic)
Potential safety liabilities associated with target modulation
Clinical Trial Design/Feasibility
Potential to generate intellectual property
Clinical Differentiation
•
How mechanism might provide an advantage over current therapies
Alignment with Pfizer strategy to ensure project uptake into pipeline
•Pfizer Confidential
16
Diversity of Biotherapeutic Formats
Monoclonal antibody therapeutics
•Human
•Antibodies
•Humanized
•Antibodies
• Platforms to generate fully human monoclonal
antibodies
• Humanization technologies
Non-antibody biotherapeutics
•Fc Fusion
•Proteins
•Therapeutic
Proteins
• Fc fusion protein
• Secreted protein
Peptide therapeutics
Novel biotherapeutic modalities
•Peptides
•Bispecific Abs
• Antibody drug conjugates (ADCs)
• CovX bodies
•ADCs
•CovX Bodies
•Pfizer Confidential
17
Focused on Monoclonal Antibodies
Antibody Modes of Action
Neutralizing Antagonist
– Antibodies that bind to a target and block an interaction
Agonist
– Antibodies that bind to a receptor and stimulate a downstream
process
Effector Function (Cell killing mechanisms)
– ADCC: Antibody-Dependent Cell-Mediated Cytotoxicity
•
Recruits macrophages, monocytes, or NK cells
– CDC: Complement-Dependent Cytotoxicity
•
Recruits complement serum proteins
•Pfizer Confidential
18
Additional Modes of Action in the CTI portfolio
Antibody Drug Conjugate (ADC)
– Antibody linked to a toxic drug via a linker; method to deliver into
specific cell types
Fc Fusion
– Used to extend half-life of peptides and/or small proteins
Peptide or Protein
– Often requires modification to become drug-like
•Pfizer Confidential
19
Proposals have been funded across many therapeutic areas
Funded Proposals (20)
Other (2)
10%
Rare Diseases,
(3) 15%
Oncology (7)
35%
Inflammation &
Immunology (3)
15%
Cardiovascular
and Metabolic
Diseases (5)
25%
CTI received over 350 proposals across our network in 2011
ranging from ideas/validated pathways to pre-existing mAbs
•Pfizer Confidential
20
CTI Project Portfolio
Stage-gate
1
0
Early-Stage
Discovery
2
Lead
Identification
3
Lead
Optimization
5(IND)
4
Lead
Development
Pre-clinical
Development
6(POM)
Clinical
Development
mAb (17)
Peptide
ADC (1)
Protein
Fusion Protein (3)
Inflammation and
Immunology
Oncology
CV MED
NeuroSci
•Pfizer Confidential
Rare Disease
Other
CTI Case Study: Humanized Antibody Program
Background:




Cell surface antigen target up-regulated on tumor cells
Antigen expressed on few normal tissues
Target not down-regulated upon antibody binding
Mabs in hand
 Aim: To generate a humanized mAb with the following modes of action:
 Antibody effector function: ADCC/CDC
 Potential opportunity to generate an ADC (antibody drug conjugate) given
selective expression on tumor cells
POM trial:
(1) Incorporate patient stratification to enhance POM measures (e.g. IHC, mutation status)
(2) Measurable endpoints in line with pre-clinical activity
 Measurable biomarker deposition in tumor biopsies (CDC)
 Demonstrate increase in tumor necrosis and presence of immune infiltrate in post-treatment
biopsies (ADCC/CDC)
(3). CT scans to monitor tumor regression
•Pfizer Confidential
22
CTI Case Study: MOA via Target Modulation
Background:




Target antigen is a cell surface receptor located on cells in the blood and intestinal tissue
Genetic markers in the receptor are associated with Inflammatory Bowel Disease
These genetic markers define a “high risk” IBD population with elevated receptor levels
Dysregulation of pathway also occurs in this subset of patients
 Aim: To generate a mAb to block receptor activity and inhibit down-stream
signaling, reducing the inflammatory cascade in patients whose disease
is driven by this defined pathway
POM Trial:
(1) Use genetically defined “high risk” and “low risk” patient subgroups for POM.
(2) Measurable endpoints in line with pre-clinical activity
.Evidence of inhibition of pathway activation in blood cells pre- and post-treatment.
 RNA signature in gut biopsies provides further evidence of reduced inflammatory cascade.
(3) Known measurements from serum and stool samples pre- and post treatment provide
additional mechanistic information.
•Pfizer Confidential
23
Inaugural CTI-UCSD/SBMRI Collaborations
Dr. Carl Ware (SBMRI)
Dr. Michael Karin (UCSD)
Distinguished Professor of
Pharmacology; Head – UCSD
Laboratory of Gene Regulation &
Signal Transduction
Professor, Laboratory of Molecular
Immunology
•Pfizer Confidential
24
Submitting a Proposal to CTI
CTI Proposal Solicitation & Selection Process
Scientifically Rigorous, but Light on Bureaucracy
1
CTI Conducts a Call for Proposals – Annually at each AMC
2
PIs Submit a 2-3 page, Non-confidential Pre-proposal for Consideration
3
CTI Convenes a Local Joint Steering Committee to Select Finalists
4
Finalist PIs Author a Confidential Full Proposal, Working Together with a CTI Scientist
5
Joint Steering Committee Reviews Full Proposal and Selects Projects for Funding
Proposals are selected for funding within 3 months of submission
•Pfizer Confidential
•26
Evolving the Request for Proposal (RFP) Search Process
From Broad to Targeted
CTI Project Identification
Version 1.0: Broad RFPs
CTI Project Identification
Version 2.0: Targeted RFPs
Targeted
RFP
Identified
Disease Areas
of Interest to
Pfizer
Broad RFP
Disease Agnostic
Agreement on
Top Projects
with Pfizer
•
•
350+ proposals
20 projects funded
across many therapeutic
areas
Focused Review –
‘Translatability’
•
•
New approach to foster a deeper
partnership with AMCs
Upfront link to Pfizer research
and commercial strategy
Key Question: What are the specific areas of research that Pfizer/CTI is interested in?
•Pfizer Confidential
•27
Request for Proposal – Inflammation
(Systemic Lupus Erythematosus / Lupus Nephritis)
Proposals are sought for novel large molecule applications with a path to a clinical
proof of mechanism study†
Clinical
Concept
Mechanisms
of interest
Precision
Medicine
New and more effective treatments that can induce and maintain remission
- Prevention of underlying dysregulation of B- and T- cells
- Modulation of innate immunity
- Targeting or interrupting inducers of persistent immune activation/inflammation
- Inhibition or modulation of inflammatory processes involved in flares (renal, synovial
or cutaneous)
- Regulation of handling and clearance of apoptotic bodies
- Promotion of immune homeostasis and immunoregulation (i.e., functional tolerance).
It is preferred if submissions incorporate a hypothesis-driven strategy for patient
selection, i.e. rationale for patient subset where drug would be most efficacious
•Pfizer Confidential
28
Request for Proposal – Renal Disease
(Kidney Injury/Lupus nephritis, IgA Nephropathy)
Proposals are sought for novel large molecule applications with a path to a clinical
proof of mechanism study†
Clinical
Concept
Mechanisms
of Interest
Precision
Medicine
• Novel approaches (targets, pathways or interventions) that would alter the course
of a disease which directly or indirectly results in kidney injury and failure
•
•
•
•
- Block intrarenal inflammation
- Regulation of leukocyte-endothelial cell interactions
- Prevention of tubular atrophy and interstitial injury
- Inhibition of specific components of the immune response related to renal
damage (i.e., aberrant mesangial Ab:IC deposition or handling).
• - Approaches aimed at promoting responses leading to improved renal function,
such as repair and/or restoration of renal epithelium and nephron integrity)
• It is preferred if submissions incorporate a hypothesis-driven strategy for patient
selection, i.e. rationale for patient subset where drug would be most efficacious
•Pfizer Confidential
29
Request for Proposal – Cardiovascular
(Congestive Heart Failure, Post-Myocardial Infarction and Acute Coronary Syndrome)
Proposals are sought for novel large molecule applications with a path to a clinical
proof of mechanism study†
Clinical
Concept
Mechanisms
of Interest
Precision
Medicine
• Cardiac remodeling events post-MI and in CHF leads to progressive deterioration
of health with few options for patients and physicians.
• Reduced mortality, CV events, and/or improved cardiac function is the ultimate
goal
• - Those that impact extracellular matrix turnover, fibrosis, restore cardiac tissue &
function, apoptosis & proliferation, cardioprotection and neovascularization.
• - Novel mechanisms that impact endothelial repair (beyond standard of care) such
as plaque stabilization and dissolution, mast cell & macrophage regulation
• Defined patient populations at highest risk of CV events that would most benefit
most from this therapeutic approach is required
•Pfizer Confidential
30
2012 Proposal Process Flow and Timeline
Jun
2012
UCSD
Jul
2012
Aug
2012
Sep
2012
Targeted
Call for
Proposals
Oct
2012
Stage I
Preproposal
Nov
2012
Dec
2012
Stage II
Fullproposal
Proposal
Review
JSC
Meeting
Decision
Making
Meeting
1:1 meetings with the Office of Contract and Grant Administration (OCGA) and CTI staff in
September and October
2–3 page non-confidential Pre-Proposals to be submitted to the Office of Contract and
Grant Administration (OCGA) by October 19th
If selected, a full confidential proposal co-authored by academic PI and CTI scientist will be
submitted to the JSC by mid December
Funding Decisions to be made in early 2013
•Pfizer Confidential
31
Next Steps
An open, informal discussion session has been scheduled after
today’s presentation in this room for PIs in attendance to discuss their
research with CTI colleagues
– Please do not disclose any confidential information
If interested, please contact the Office of Contract and Grant
Administration (OCGA) to inquire about meeting with CTI staff prior to
submitting a proposal
– Cortlandt Urquhart, [email protected], 858-534-0244
– Jennifer Ford, [email protected], 858-534-3335
Pre-proposals due to the Office of Contract and Grant Administration
(OCGA) by October 19th
To learn more and obtain the pre-proposal template, please visit
https://cti.ideareach.com/ and create a user profile
•Pfizer Confidential
32
Incentives to collaborating with CTI
Partnering leading academics with drug discovery experts to rapidly translate novel research from
discovery into meaningful mechanistic studies in the clinic
Co-lead project team to ensure sustained involvement from discovery to clinic
Collaborative use of Pfizer’s proprietary drug discovery tools and technologies
Support for IND- & clinical-enabling functions (e.g., toxicology, regulatory, etc.)
Co-location near academic laboratory with access to Pfizer scientists,
technology, and drug development expertise
Equitable IP and publication rights
Success-based funding/financial incentives (milestone & royalty payments)
Comparable attrition and funding success rate to NIH R01 grant
Streamlined but scientifically rigorous 3 month awarding process from time of
proposal submission
•Pfizer Confidential
33
Acknowledgements – CTI Leadership
Tony Coyle
Rick Lindberg
Alex Fayne (RIP 2012)
Michael Norsen
CSO & VP
CTI
Site Head
CTI – California
Chief Operating Officer
Strategy & Operations CTI
Alliance Management
Strategy & Operations CTI
Jose Carlos Gutierrez-Ramos
Margi McLoughlin
Louisa Daniels
SVP
Biotherapeutics Research
Sr. Director
WW Bus Dev & Innovation
VP and Assistant
General Counsel
34
Questions

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