ALAXIA SAS, France

A company dedicated to orphan drugs

Feasibility study of OSCN- and Lactoferrin (Meveol®)

nebulization for Cystic Fibrosis patients

Meveol program supported by

34th European Cystic Fibrosis Conference

Hamburg 8-11 June 2011

Workshop 20 - Progress in Antimicrobial Therapies

Feasibility study of OSCN- and Lactoferrin (Meveol®)

nebulization for cystic fibrosis patients

2 complementary studies

- 1 study on nebulizer performance, for aerosol choice

- Done by Aerodrug

- 1 study, In Vitro & In Vivo efficacy (no aerosol used)

- Done by CER (M abscessus, PAO),

- Done by Alaxia (Burkholderia cepacia, Burkholderia dolosa),

Meveol by Alaxia

• Meveol is a fixed composition of OSCN-/Lactoferrin, 2 API

• OSCN-/Lactoferrin act as antimicrobials (planktonic, Biofilm)

– As seen in many publications

– As we show In Vitro, In Vivo

• Inhalation use product

– Topical action

– Mesh Nebulizer compatible

• EMA & FDA designated as Orphan drug,

• Phase I planned next year

Nebulizer choice

• Test of 5 neb on aerodrug platform

• VMD caracterisation

• Inhalable fraction, Respirable fraction

• Alaxia choice

B A C D E

Jet and mesh nebulizers

- The NL9M®/ABOX+ (DTF, France -A) and the Pari LCSPRINT®/Turboboy (Pulmomed, France -B).

- The E-Flow® (Pari, Germany -C), the Micro-Air® (Omron, Japan -D) and the Aeroneb® Go (Aerogen, Ireland)

associated with the Idehaler-Pocket® chamber (Aerodrug, France) (-E).

- Three copies of each nebulizer and their mouthpieces were used and tested in duplicate

Nebuliser tested

Aerodrug platform, Tours

Results acheived with Meveol

mean±SD VMD (µm) Inhalable

fraction (%)

Respirable

fraction (%)

Nebulization

time (min)

Aeroneb® Go/

Idehaler-Pocket® 4.3 ± 0.5 57 ± 1 31 ± 3 9.8 ± 0.4

E-Flow® 4.5 ± 0.9 47 ± 13 26 ± 11 10.6 ± 0.1

Micro-Air® 5.7 ± 0.2 23 ± 5 8 ± 1 36.2 ± 5.0

NL9M® 5.7 ± 0.2 30 ± 5 12 ± 2 9.7 ± 1.1

Pari LCSPRINT® 3.4 ± 0.5 38 ± 6 20 ± 1 24.2 ± 8.1

Meveol challenge tests

• In Vitro

– vs Mycobacterium abscessus (ATCC 19977) done by CER

– vs Burkholderia cenocepacia (J2315) done by Alaxia

– vs Burkholderia dolosa (AU 0158) done by Alaxia

• In Vivo (Mice)

– vs Pseudomonas aeruginosa (Strain isolated from CF patient),

done by CER

In Vitro protocols

• Controls, Meveol

• Meveol added one time only at T0

• Trials in bacteria growth media

• Petri dishes in duplicate, 3 dilutions at least

• Reading 24h and confirmation 48h (except M abscessus,

7days)

Meveol added at T0 only

In growth media solution Strain ATCC 19977

0,00

2,00

4,00

6,00

8,00

10,00

12,00

0 10 20 30 40 50

Incubation time (h)

Culture control

Culture with Meveol

(lo

gC

FU

/mL)

Mycobacterium abscessus

Meveol added at T0 only

In growth media solution

Meveol 1000 Meveol 500 Control

On petri dishes (Sample taken after 3h contact time) After 24h contact time on B dolosa in TSB (T0 6 log)

Meveol 1000 Meveol 500 Control

Meveol added at T0 only

In growth media solution

In Vivo protocol • In Vivo results

• Species : Mice

• Breed C57Bl6

• Infection by mucoïd Pseudomonas aeruginosa (isolated

from Cystic Fibrosis patients)

• Meveol treatment (Instillation) started 24 hours after

animal inoculation

• Second instillation 48 hours after infection

• Sacrifice 72 hours after infection

Protocol agreed by CER Ethic committee on

animal welfare

In Vivo results achieved

Mice lung 72h after infection by 106 CFU mucoid pseudomonas aeruginosa

0,0

0,5

1,0

1,5

2,0

2,5

3,0

3,5

4,0

4,5

5,0

Infected control Treated

Lu

ng

bacte

ria (

log

CF

U/g

)

N=12

Average : 1,5

SD : 0.5

N=9

Average : 3,1

SD : 0.4

≠1,6 log

2 trials, same efficacy acheived

P < 0.05

ALAXIA SAS

3-11 Rue Perlerie

F- 69120 Vaulx en Velin

Phone : +33.(0)4.72.81.09.26

Fax : +33.(0)4.78.41.17.79

Email : contact@bioalaxia.eu

www.meveol.eu

Cathy, Jacky

Pilou, Cezar

MEVE L

Thank you for attending

Program supported by

www.alaxia-pharma.eu