Le Levosert : fruit d'une collaboration continue entre une Spin-off et l'Université par...

Au cœur d’une spin-off

Valérie GORDENNE - ODYSSEA Pharma, a member of Uteron Pharma Eric POSKIN - MITHRA Pharmaceuticals

Le Levosert : un produit aboutit grâce à une collaboration continue entre une Spin-off et l’Université

Avec le soutien de :

Valérie Gordenne

DG Odyssea Pharma

Eric Poskin

Spokesman Mithra

Levosert®

né & développé

Au coeur d'une spin-off

Levosert®

un produit né de l’histoire d’une Spin-off (Mithra Pharmaceuticals)

Levosert®

un produit aboutit grâce à une collaboration continue entre une Spin-off

et l'Université.

Levosert®

un produit arrivé à maturité au sein d’Uteron Pharma

Histoire d’un développement

Au coeur d‟une Spin-off ?

Research, Expertise (medical & pharmaceutical)

Mithra University

R&D:

40 millions € invested till 2009

100 M€ will be invested from 2009 till 2017

Objective/Mind Approach :

„Cross fertilization‟

A “spin off”

Research, Expertise (medical & pharmaceutical)

Mithra University

Objective/Mind Approach :

„Cross fertilization‟

A “spin off”

SYNERGIES

Synergies

I. A new/another

Economic

Model / Approach ?!

Which is not JV‟s, …

Based on

MEETING (Vs Confrontation) of different worlds

(i.t.o. times, objectives, cultures)

Synergies

II. A SPIN-OFF

IS FIRSTLY

A STORY/MEETING

OF PEOPLE Synergy too

(no recipe)

III. Synergy

is

a permanent process

(The way of a Sustainable Growth)

IV. Synergy

Is not

a virtual process

Example of Levosert :

Initiating new synergies

to root the growth...

Example of Levosert :

Rooting the growth

to give credibility

to Levosert ...

Products

Structures

Synergies Credibility

Levosert

Odyssea/

Uteron Pharma

Synergies Credibility

1997 1998 1999 2000 2003 2004 2005 2006 2008 2010 2011 2012

De l‟idée à aujourd‟hui …

Externalisation

du Levosert

1997 1998 1999 2000 2003 2004 2005 2006 2010 2011 2012

De l‟idée à aujourd‟hui …

2008

Financement

du Levosert par MED360

(100M$ )

1st Levosert

Environment

1997 1998 1999 2000 2003 2004 2005 2006 2008 2011 2012

De l‟idée à aujourd‟hui …

2010

Année de transition

Réorganisation

de l’Actionnariat & des Structures

Levosert

Levosert -20® : Présentation

Intra-Uterine Device

releasing

Levonorgestrel.

Levosert -20® : Présentation

« Headings »

High risk development

non conventional pharmaceutical form

low expertise

non conventional excipient

non conventioanl process

custom made equipment

regulatory complexity

Estimated budget : 2 000 000 €

Levosert -20® : Présentation

BUT

High Interest

No competitors

Expertise gain in a niche

Levosert -20® : Présentation

I. Proof of concept : Empirical development

• Step 1 : Reservoir-membrane system formulation

•Selection of excipient : medical device application drug application

•Major critical attribute : in-vitro release rate

• Step 2 : Process development

•Semi-automatic process for reservoir production – full manual assembling process

•Development of new equipement

•World Patent granted = alternative to data protection

Minimal investment In vitro demonstration of Equivalence

Main Development Steps

Proof of concept : In vitro LNG release profile

Levosert-20 (prototype) and Mirena®

0

2

4

6

8

10

12

14

16

18

20

22

24

0 200 400 600 800 1000 1200 1400 1600 1800

LNG

in

vit

ro r

elea

se r

ate

(µg/

24

h)

Time (Day)

Mirena (N=4)

Levosert prototype (N=3)

Main Development Steps

0

1000000

2000000

3000000

4000000

5000000

6000000

7000000

8000000

2006 2007 2008 2009 2010 2011

Evolution investissements phase R&D

Equipment acquisition

Development costs

C

linic

al t

rial

init

iati

on

P

roof

of concept

Main Development Steps

c

on

solid

ated

de

sign

1997 1998 1999 2000 2003 2004 2005 2006 2008 2010 2011 2012

Externalisation

du Levosert

Main Development Steps

In Vivo Development

• 1700000 € of investment

•One indication

• 1 year study + 2 years

extension period

• Partnership (Medicines360)

Odyssea Creation

• 3500000 € of investment (Leasing)

• process validation, clinical batches

for US

Proof of concept

Main Development Steps

1997 1998 1999 2000 2003 2004 2005 2006 2010 2011 2012 2008

Financement

du Levosert par MED360

(100M$ )

Main Development Steps

0

1000000

2000000

3000000

4000000

5000000

6000000

7000000

8000000

2006 2007 2008 2009 2010 2011

Evolution investissements phase R&D

Equipment acquisition

Development costs

C

linic

al t

rial

init

iati

on

P

roof

of concept

Main Development Steps

c

on

solid

ated

de

sign

II. Consolidated Design : ICHQ8 • New Regulatory requirements for drug product (empricial method systematic

approach) • desired quality by a better understanding of the product and its manufacturing process.

• 4 steps process :

• Target Product Profile

• Quality attributes (raw materials) and Process Parameters

• Functional relationships = design of experiment

• Using the enhanced product and process understanding to establish control

strategy that will ensure product quality, safety and efficacy.

Main Development Steps

III. Insertion system : Medical Device Part

• Regulations :

DIR 93/42/EEC - ISO 13485 (EU)

21CFR820 - QMS (US)

Principles :

•Every product covered by European Directive has to satisfy to Essential

Requirements in terms of safety and efficacy

• The manufacturer has to proove the conformity to the Essentials

Requirements .

Main Development Steps

User Requirements Specifications

Performance Qualification

Functional Specifications

Design Specifications

Operational Qualification

Installation Qualification

Device

ENGINEERING QUALIFICATION & VALIDATION

IQ / OQ Reports

Validation reports Reports

Change control

Vérification

Design control (ISO 13485) et mangement des risques (ISO 14971)

Evaluation des propriété

physique et chimique

Choix des matériaux

Biocompatibilité (ISO

109993)

Test fonctionnels de

laboratoire

Evaluation par utilisateur / tests cliniques

IV. Insertion System

Main Development Steps

Main Development Steps IV. Insertion System

2011 2012 2013

DCP Levosert IUS UK/H3030/01/DC

Hybrid Application 10(3) (no data protection) Pivotal study: EU Menorrhagia Outcome 3 indications – 3 Years RMS : UK Mithra CMS : BG, CZ, EE, HU, LT, LV, PL, RO Gedeon Richter NL Mithra

MHRA Expert

Advisory meeting

End of

procedure

National

approval

Market Authorization

Conclusions: • Développement d’un produit unique

pas de concurrence • Grâce à Fertilisation / Synergie - Contribuer au développement d’une structure et vice et versa (ex Odyssea) - Identifier compromis entre investissements cliniques vs positionnement pdt sur le marché • Complexité du projet dans sa globalité : RA / QA vs timing Developpement

Et après …

• 2012 : Enregistrement in UK ( + 9 pays européens)

• 2013 : Enregistrement in B

• 2014 : Enregistrement in Reste du monde (hors USA)

• 2016 : Enregistrement in USA

…

Merci pour

votre écoute