1. A new way to Drug Discovery

2. The 3D-Screen technology
A new way to Drug Discovery
> Biological products exert their function through a specific tri-dimensional conformation that controls
their interactions with cellular partners
Known
Ligand
TARGET
TARGET
PROTEIN
Biological
PROTEIN
Response
Dramatic or subtle conformational
changes
®
2 March 26, 2012© 2000-2011 Vivalis — All rights reserved— CONFIDENTIAL

3. The 3D-Screen technology
Basic Principle
ON OFF
Native conformation of the
target is recognize by the 3D-
Sensor
TARGET
PROTEIN Identification in a single
assay of:
COMPOUND
TARGET LIBRARY -Agonist
PROTEIN -Antagonist
- Allosteric Modulator
(Inhibitor & Activator)
- Cellular cofactor
TARGET modulator
PROTEIN
Screening for CONFORMATION changes
®
3 March 26, 2012© 2000-2011 Vivalis — All rights reserved— CONFIDENTIAL

4. 3D-SCREENTM Technology
Molecular principle & Opportunities offered
COMPOUND
AD LIBRARY
Peptide-sensor
CELLULAR
COFACTOR
HCV
CELLULAR
COFACTOR
TARGET
CELLULAR
COFACTOR
HUMAN CELL
DBD
5’ Luciferase 3’
UAS
DISCOVERY OF THE BROAD RANGE OF DRUGS
- Agonists (DAA)
AD: Activating Domain - Antagonists (DAA)
DBD: DNA Binding Domain
UAS: upstream Activating Sequence
- Allosteric Modulators (DAA)
- Disruption of protein interactions (HTA)
- Modulators of cellular cofactors (HTA) ®
4 March 26, 2012© 2000-2011 Vivalis — All rights reserved— CONFIDENTIAL

5. 3D-SCREENTM Technology
Molecular principle & Opportunities offered
COMPOUND
LIBRARY
CELLULAR
AD
COFACTOR
Peptide-sensor
HCV
CELLULAR
TARGET
COFACTOR
CELLULAR
COFACTOR
HUMAN CELL
DBD
5’ Luciferase 3’
UAS
X DISCOVERY OF THE BROAD RANGE OF DRUGS
- Agonists (DAA)
AD: Activating Domain - Antagonists (DAA)
DBD: DNA Binding Domain
UAS: upstream Activating Sequence
- Allosteric Modulators (DAA)
- Disruption of protein interactions (HTA)
- Modulators of cellular cofactors (HTA) ®
5 March 26, 2012© 2000-2011 Vivalis — All rights reserved— CONFIDENTIAL

6. 3D-Sensor: The Heart of 3D-Screen technology
A powerful cell-based assay to discover allosteric & cellular cofactor
modulators of HCV NS5B polymerase IN ONE SINGLE ASSAY
®
6 March 26, 2012© 2000-2011 Vivalis — All rights reserved— CONFIDENTIAL

7. 3D-Sensor: The Heart of 3D-Screen technology
A powerful cell-based assay to discover allosteric & cellular cofactor
modulators of HCV NS3 protein IN ONE SINGLE ASSAY
ORTHOSTERIC MODULATORS ORIGINAL MODULATORS
Peptidomimetic anti-protease inhibitors Small molecule (< 500 D)
Linear Macrocyclic CVVS-060215 (VIVALIS)
(e.g VX950) (e.g BILN2061) (EC50 =13 nM)
+ + +
VIVALIS SMALL MOLECULE UNDER LEAD OPTIMIZATION
WHICH IS NOT A PEPTIDOMIMETIC OR A MACROCYCLIC MOLECULE
UNLIKE MOST COMPETITOR MOLECULES
®
7 March 26, 2012© 2000-2011 Vivalis — All rights reserved— CONFIDENTIAL

8. 3D-Sensor: The Heart of 3D-Screen technology
A powerful cell-based assay to discover any modulators’ class of
Estrogen Receptor alpha ACCORDING SCREENING SPECIFICATIONS
CONFORMATION SENSITIVE PEPTIDES CAN BE IDENTIFIED THAT ARE SENSITIVE
TO AGONISTS, ANTAGONISTS OR BOTH
NO E2 4OHT 9cRA DEX
LIGAND agonist antagonist RA ligand GR ligand 1
10nM 50µM 0.5µM µM
Selected peptide sensitives to
all types of ligands
Selected peptides sensitive to
antagonist ligands only
Selected peptide sensitives to
agonist ligands only
SELECTION OF THE 3D-SENSOR CANDIDATE ACCORDING TO THE INTENTED
SCREENING OBJECTIVES
®
8 March 26, 2012© 2000-2011 Vivalis — All rights reserved— CONFIDENTIAL

9. 3D-Sensor: The Heart of 3D-Screen technology
A powerful cell-based assay with a VERY HIGH SENSITIVITY
3D-Sensor sensitive to conformational changes of Retinoic Acid Receptor (RAR) induced by the
binding of all-trans-RA only or 9-cis-RA & all-trans-RA in Yeast cells
Inhibition by 9-cis-RA & all-trans-RA Inhibition by all-trans-RA only
RA : RETINOIC ACID 9-cis-RA All-rans-RA
Selective identification of 3D-Sensor sensing subtle differences in conformational
changes induced by the structurally close at-RA and 9cis-RA ligands
®
9 March 26, 2012© 2000-2011 Vivalis — All rights reserved— CONFIDENTIAL

10. The 3D-SCREENTM Technology
An innovative platform for new classes of drugs
1. A unique proprietary human cell-based, target-oriented, HTS-compatible
assay to screen for small molecules that specifically alter the 3D structure of a
target protein in their natural cellular environment.
2. A powerful platform to discover orthosteric, allosteric & cellular cofactor
modulators IN ONE SINGLE ASSAY, including molecules that cannot be
identifed using tradional cell-based assays
3. Validated with well established therapeutic targets (Hepatitis C, Nuclear Receptors)
4. Applicable to any validated therapeutic target (viral proteins, nuclear receptors, kinases, …)
A novel drug discovery platform that has the potential to produce clinically
differentiated products across multiple therapeutic areas
®
10 March 26, 2012© 2000-2011 Vivalis — All rights reserved— CONFIDENTIAL

11. ®
Merci
Thank You
ありがとうございました