Alaxia slides, hamburg ECFS congress

1. Feasibility study of OSCN- and Lactoferrin (Meveol®)
nebulization for Cystic Fibrosis patients
A company dedicated to orphan drugs
34th European Cystic Fibrosis Conference
Hamburg 8-11 June 2011
Workshop 20 - Progress in Antimicrobial Therapies
Meveol program supported by
ALAXIA SAS, France

2. 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),

3. 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

4. Nebulizer choice
• Test of 5 neb on aerodrug platform
• VMD caracterisation
• Inhalable fraction, Respirable fraction
• Alaxia choice

5. Nebuliser tested
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
A B C D E
Aerodrug platform, Tours

6. Results acheived with Meveol
mean±SD VMD (µm) Inhalable Respirable Nebulization
fraction (%) fraction (%) time (min)
Aeroneb® Go/
4.3 ± 0.5 57 ± 1 31 ± 3 9.8 ± 0.4
Idehaler-Pocket®
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

7. 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

8. 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)

9. Mycobacterium abscessus
Meveol added at T0 only
In growth media solution Strain ATCC 19977
12,00
10,00
8,00
(logCFU/mL)
6,00
Culture control
Culture with Meveol
4,00
2,00
0,00
0 10 20 30 40 50
Incubation time (h)

10. Meveol added at T0 only
In growth media solution

11. Meveol added at T0 only
In growth media solution
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 1000 Meveol 500 Control

12. 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

13. In Vivo results achieved
5,0
4,5 Mice lung 72h after infection by 106 CFU mucoid pseudomonas aeruginosa
4,0
3,5
Lung bacteria (log CFU/g)
3,0
2,5
≠1,6 log
2,0
1,5
1,0
N=9
Average : 3,1 N=12
0,5 Average : 1,5
SD : 0.4 P < 0.05 SD : 0.5
0,0
Infected control Treated
2 trials, same efficacy acheived

14. MEVE L
Cathy, Jacky
Pilou, Cezar
Thank you for attending
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
Program supported by
www.meveol.eu www.alaxia-pharma.eu