5 minutes of fame

1. Accelerating Development
Ron Connolly
October 1, 2012
CORPORATE OVERVIEW

2. Frontage Snapshot-An Integrated R&D outsourcing company
 Headquartered in Exton, Pennsylvania, U.S.A. (Established 2001)
Locations
 New Jersey, Shanghai, Beijing, Zhengzhou, Changchun
 Preclinical through clinical-stage • DMPK,
Service Offerings • Biologics & Bio-analytical Services
drug development and clinical
services: • CMC - drug development
• Clinical studies and biometrics
 Over 200 customers (>85% returning) mainly in the US, EU, Japan and China:
Customers • Global Top 10, mid-size and virtual pharmaceutical and biotech firms,
• Government agencies and public health concerns (NIH, BARDA, NIAID, foundations)
• Leading Chinese generic and innovative drug companies
Employees  280+ employees - Close to 70% of scientist team with advanced degrees
 US:
• 80,000 sq.ft. Bioanalytical / DMPK lab and Animal Facility in Exton, PA (AAALAC)
• 26,500 sq.ft. CMC services operation including API synthesis lab, analytical,
formulation development, and GMP manufacturing of clinical trial materials (CTM)
Facilities • 15,000 sq.ft., 88-bed Phase I-II clinical research facility in Hackensack, NJ
 China:
• 16,000 sq.ft. bioanalytical lab, one of the largest in Shanghai
• 30,000 sq.ft. CMC lab and GMP CTM facility in Beijing
• Clinical facilities in Zhengzhou (120 beds), Changchun (82), and Nanjing (50)
CORPORATE OVERVIEW

3. US and China: Round-the-Clock Operations
Beijing, PRC
• Clinical Services
• Regulatory Affairs
• CMC Services
• GMP Consulting
Shanghai, PRC
• Bioanalytical
• Biologics
• DMPK
Exton, PA (2 locations) • Analytical Services
• Headquarters
• Bioanalytical/Biologics
• DMPK
• CMC Services Hackensack, NJ Hospital based Phase I-IIa units
(API, Analytical, PRD, CTM mfg) • 88-bed Phase I-IIa Clinic 120-bed Zhengzhou University
• Regulatory Affairs • Late phase clinical studies 82-bed The First Teaching Hospital of Jilin University
• GMP Consulting • Data management/support 50-bed Nanjing City First Hospital
CORPORATE OVERVIEW
3

4. CPSA 5-MINUTE INTRO
Making discoveries that accelerate development
1. LC/MS/MS quantification of mAb (MW ~126K)
2. Developing a formulation for a "brick" material
that is insoluble
3. Performing dose escalation study arms in 5 days
CORPORATE OVERVIEW

5. LC/MS/MS QUANTIFICATION OF ANTIBODY IN SERUM AND CSF
A Humanized IgG1 mAB
developed as a potential
therapeutic agent for
Alzheimer disease (AD)
Challenge
ELISA assay sensitivity
(LLOQ of 6 ug/mL),
IgG1 mAB
primary Ab was limited.
Target LLOQ:
Serum assay = 500 ng/mL,
CSF assay = 5 ng/mL
CORPORATE OVERVIEW

6. ALTERNATIVE LC-MS/MS ASSAY STRATEGY
Solution
 Developed LC/MS/MS method with selected surrogate
peptides (LC/MS/MS optimization)
 Developed a sample processing procedure using
enrichment approach and digestion
 Determined best IS approach
(Antibody analog vs deuterated surrogate peptide)
Results
 Client successfully utilized LC/MS/MS method in
Phase I studies and moving to Phase II
CORPORATE OVERVIEW

7. FORMULATION DEVELOPMENT FOR INSOLUBLE DRUGS
Challenge
More compounds in development with poor solubility
• Roughly 65% of discovery compounds have solubility <100 µg/mL
Solutions
• Solid amorphous dispersion
• Pharmaceutical co-crystals
• Self-emulsifying and self-microemulsifying drug delivery systems,
• Suspension or Emulsion Parenteral Dosage Form
Results
• Utilizing Quality by Design principles to create robust formulations
• Enhanced drug permeability and delivery in-vivo
CORPORATE OVERVIEW

8. CLINICAL - INTEGRATED OPERATIONS WITH FAST TURNAROUND
Case Study: Open-label single-dose, two-period crossover study to
assess BE of test and reference formulations
 Contract signing to BA/PK data in less than 5 weeks;
 60 subjects and nearly 3000 samples
• Two-in-one method developed and validated within 2 weeks
 Contract signed: 14 Nov of contract signing (8 calendar days including Thanksgiving!).
 IRB submission: 15 Nov
• 2949 samples analyzed Dec 15-19. No run failures occurred
 IRB approval: 21 Nov
 Subject screening: 22 Nov • 10 LC/MS/MS systems, 10 chemists, 34 runs
 FPFV: 03 Dec
 LPLV: 13 Dec • QC’d data Dec 21; QA’d data Dec 29.
 Samples Shipment: 14 Dec
• Preliminary Bioequivalency Evaluation included with QC data
 BA/PK data to sponsor: 21 Dec
 TLFs to sponsor: 06 Jan • ISR– 300 analyzed with only 1 sample for analyte-1 and 7
samples for analyte-2 falling outside of the criteria (Guidance
allows 15%).
• Final Report to the client within agreed upon timeline and
consistent with CLIENT’s STYLE GUIDE.
CORPORATE OVERVIEW

9. FRONTAGE ACCELERATES SOLUTIONS
 DISCOVERS solutions to tough technical challenges
 DELIVERS high quality data on-time and on-budget
 DEDICATES experienced personnel to projects for
efficient execution
www.frontagelab.com
1-610-232-0100
CORPORATE OVERVIEW