‘Van de heilige academische Mono naar

de realistische Alkense Combo’

Dr. Erik Buntinx, psychiatristFounder – Inventor – CEO

PharmaNeuroBoost

PNB01: A Paradigm Shift in Treating Major Depression ?

1. Slow onset2. Insufficient efficacy3. Long term outcome poor

4. Remission still challenge

Impact on treatments• Inconsistent treatment paths• No treatment guidelines

Unmet Need of SOC

1. Early effect2. Sustained efficacy3. Effect maintained over time

4. Higher remission rates

Impact on treatments• Logical first line, no waste• Allows clear treatment guidelines

Product Differentiation (Key Value Drivers)

+

Current Mono Antidepressants (SOC):Unmet Need vs. Product differentiation

++

+

NEED FOR A FASTER, MORE EFFECTIVE FIRST LINE AD

2

3

Inspired by the late Dr. Paul

Dr. Paul Janssen (1926-2003) was one of the 20th century's most innovative and inspiring pharmaceutical researchers.

• In 1953, Dr. Paul established Janssen Pharmaceutica, N.V.• Responsible for many breakthroughs in several fields of disease,

including pain management, psychiatry, infectious disease and gastroenterology

• In 1961, Janssen Pharmaceutica N.V., became part of the Johnson & Johnson Family of Companies.

Through his constructive feedback Dr. Paul inspired and motivated Dr. Erik Buntinx to undertake a project to establish the scientific rationale and validation of the results from his original clinical observations.

Finding the Matching Compound

4

Dr. Erik Buntinx consulted various scientific libraries including data derived directly from J&J

• First compounds were rejected based on negative safety profile• Discovered the unique characteristics of Low-Dose

Pipamperone (5-15 mg/day) i.e.• High Selectiveness towards Serotonin 2a and Dopamine D4

Receptors• A unique low plasma protein binding profile (36%) • A unique positive safety profile

• The internal J&J safety file (*) of Pipamperone showed an extremely low incidence of (serious) adverse events

(*) Disclosed by J&J to PNB

1. E. Buntinx et al, Int. J. Neuropsychopharmacology, 2008

Predicted relative in-vivo receptor binding (%) vs. average plasma, from in vitro data

0

20

40

60

80

100

0 10 20 30 40 50

p ip am p e ro ne , C avg at s te ad y s tate (ng /m l)

% b

indi

ng5H T 2a

7 .5 m g

5 m gD 4

D 2

2 .5 m g

1

H 1

6 m g

Pipamperone: a unique,

combined highly selective

5-HT2A/D4 antagonist1

BID

PNB Technology Platform

Concept - the Boosting Agent: Low Dose Pipamperone

5

PharmaNeuroBoost Mission

PNB01Citalopram

Boosting Agent

+

PNB02Risperidone +

PNB03Escitalopram +

Boosting effectiveness of Standard of Care drug treatment in CNS:

A paradigm shift

Current Worldwide IP

Protected Products

PNB04Paliperidone +

6

2024 (EU)

2026(US, EU, JP, CND)

2.5 BLN USD (est.)

2 BLN USD (est.)

Dec. 2012: Top Line Results on

PNB01 Phase III Trial PNB02 Phase IIa Trial

PNB Product Pipeline

Superior CNS Products in Major Indications

COMPOUND Pre-clinical Phase I Phase IIPhase III

(FDA Approved Protocol & SAP Under SPA)

Global Peak Sales

Patent Expiry (Region)

PNB02&

PNB04

PNB01&

PNB03

Rapid Acting AD with a Superior Early and Sustained Response Rate

in MDD

All Patients randomized in the US (n=555)

First PatientsEnrolled in BelgiumSuperior LT treatment

in schizophrenia, residual stage

2014

2012

7

CITALOPRAM ALONE

5-HT1A 5-HT2A D4

CIT

PIP

5-HT1A 5-HT2A D4

PIP

CIT

Antidepressant effect ++

+ PIPAMPERONE

Antidepressant effect +

PNB01: MoA for rapid acting antidepressant

PNB01

Enhancing receptor binding profile

SER

DOP

8

ESRMADRS total score (TS) reduction ≥50% from baseline and MADRS TS threshold ≤16 at week 2, 4, and 6 (combined)

Randomised, double blindPatients with moderate to severe MDD

CIT citalopram 40 mg od

PNB01pipamperone 5 mg bid + citalopram 40 mg od

Early Sustained Response (ESR) PNB01 vs. Citalopram1

1. Adapted from Wade et al. 2011 Psychol Medicine MADRS: Montgomery–Åsberg Depression Rating Scale; * Fisher exact test (2-sided)

PNB01 POC Outcomes: 1. Superior ESR

Superior Early and Sustained Response (ESR) over active treatment

n=82

9

PNB01 CIT

Drug-related Adverse Events 35.2% 43.6%

Serious Adverse Events 0.0% 1.3%

Discontinued due to AE 0.3% 1.8%

Common AEs were generally similar between groups Drug-related diarrhoea was significantly higher in the

CIT group (8.8% vs. 1.2%, P=0.032) All AE classed as psychiatric disorder occurred in the

CIT group, especially insomnia (3.8% vs. 0.0%; P=0.027)

Wade et al. Psychol Med. 2011 Feb 25:1-9

PNB01 POC Outcomes:2. Trend to Less Drug Related Adverse Events

10

Comparative effectiveness vs. Citalopram: ESR as primary end point

1. www.clinicaltrials.gov - study design: NCT01312922

PNB01-C301 Phase III Acute Efficacy Study

PNB01-C301 Objectives & Design: Superior Early and Sustained Response (ESR) over active treatment

11

Reduce biaseliminates clinician rating as a source of bias in multicenter studies1,2

Limits number of missing dataincluding those after prematurely study treatment discontinuation

Permits follow-up of drop-outs without violation of the patient’s right to discontinue participation at any time of the study

Patient-reported primary and secondary endpoints are collected

electronically (ePRO) using an Interactive Voice Response System

(IVRS) via telephone

(1) Moore HK et al.Psychoparmacol. 2006 Jun; 26 (3):321-24; (2) Mundt JC et al. J Clin Psychopharmacol. 2007 Apr; 27(2):121-5; www.clinicaltrials.gov - study design: NCT01312922

PNB01-C301 Phase III Study - ePRO

First Phase III Study using ePROfor assessment of Primary Endpoint

12

PNB01-C301 Study: ePRO data up till dateMADRS: Montgomery–Åsberg Depression Rating Scale

PNB01-C301 study – Blinded Data: Mean ePRO MADRS Total Score first 250 Pts.

13

Consistent with Mean Ratings of Investigators with mean ePRO MADRS Total Score at Baseline of 36!

Note: data are based on a preliminary blinded dataset and, therefore, are not necessarily representing the actual randomized subjects nor without warranties of any kind; www.clinicaltrials.gov - study design: NCT01312922

37%

52%

11%

0

10

20

30

40

50

60

PNB01-C301 Study - Blinded Data : ePRO MADRS Total Score

Randomized Patients: Mean, Distribution and Change at Screen and Baseline

Tota

l Sco

re

Screening Baseline

Mean = 35Mean = 36

N = 297Decrease

Equal

Increase

Change in MADRS total score from screening to baseline (% pts)

Note: data are based on a preliminary blinded dataset and, therefore, are not necessarily representing the actual randomized subjects nor without warranties of any kind; www.clinicaltrials.gov - study design: NCT01312922 14

0

10

20

30

40

50

60

77%

19%

4%

15

Screen Failures due to low MADRS total score (< 26)

Tota

l Sco

re

Screening Baseline

Change in MADRS total score from screening to baseline (% pts)

Mean = 25

Mean = 19

N = 137

Decrease

Equal

Increase

Data are based on a preliminary dataset and, therefore, are not necessarily representing the actual randomized subjects nor without warranties of any kind.

PNB01-C301 study - Blinded Data : ePRO MADRS Total Score

Conclusions

PharmaNeuroBoost (PNB) is a CNS specialty pharmaceutical company with:

A unique, IP protected and clinically proven platform boosting current standard of care

Global Development of CNS compounds Addressing unmet medical needs With a high market potential (>1B peak sales)

Most advanced product in Phase III, planned NDA in 2015

Initiated by late Dr. Paul Janssen and targeted to realize a paradigm shift in treating devastating CNS disorders

16

Questions

Thank you