Most common diseases in developed countries

30 to 50% of work absenteeism

50-60% of school absenteeism

Immunological status and age: children and elderly Air pollution Tobacco smoking Social promiscuity

Acute and Chronic Respiratory Infections1234

Risk factors of respiratory infections256

Lower respiratory tract infections

Upper Respiratory Tract Infections

Lower Respiratory Tract Infections

Common coldSinusitisPharyngitisEpiglottitisLaryngotracheitisOtitis

BronchitisBronchiolitisPneumoniaAcute Exacerbations in Chronic Obstructive Pulmonary Disease (AECOPD)

Most often viral etiologyEpiglottitis and Laryngotracheitis: Hæmophilus influenzaBacterial pharyngitis: Streptococcus pyogenes

Either viral or bacterial etiologyBronchitis and bronchiolitis: often viralCommunity acquired Pneumonia: Streptococcus pneumoniaeAtypical pneumonia: Mycoplasma pneumoniae, Chlamydia spp, Legionella, Coxiella burnetii and virusesAECOPD: Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa and viruses in 40% of exacerbations

1. Bellos et al. The burden of acute respiratory infections in crisis-affected populations: a systemic review, Conflict on Health, 4:3, 2010 2. S. Rossi et al. Efficacy and safety of a new immunostimulating bacterial lysate in the prophylaxis of acute lower respiratory tract infections, ArzneimforschdrugRes 54, no. 1, 50-56, 20043. V .Purushothama et al. Infection of the respiratory system, Medical Microbiology, Chap 93, 19964. F.Braido et al. Bacterial lysate in the prevention of acute exacerbation of COPD and in respiratory recurrent infections, International Journal of COPD, 2(3), 1-11, 20075. F. Rosaschino et al. Strategies for optimizing compliance of paediatric patients for seasonal antibacterial vaccination with sublingually administered Polyvalent Mechanical Bacterial Lysates (PMBL), Acta Bio Medica Ateneo Parmense, 75, 171-178, 20046. World Lung foundation, Acute respiratory infections Atlas, 1st ed, 2010 http://www.ariatlas.org/

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Better reduction of upper respiratory tract infections than CLBL (Chemical lysate)

Better reduction of work absenteeism than CLBL (Chemical lysate)

No patient with PMBL required antibiotic during 6 months study

Multiple inactivated strains (13) derived from the most common pathogens responsible for Respiratory Tract Infections

Mechanical lysis

Preservation of the antigenic structure

Removal of capsule

10-100 times more efficient than other lysates (single strain lysates or chemical lysates)1 in vitro

Sublingual route

Acts on each step of the whole immune cascade

Stimulates both innate and adaptive immunity

Sublingual route allows interacting directly withrespiratory mucosa to trigger a loco regional immune answerPMBL,

Optimal immunogenic profile in clinical results4

PMBL, Unique process and formulation

Original mode of action123

mean number of upper respiratory infections

Control

1.4

1.2

1

0.8

0.6

0.4

0.2

0

PMBLCLBL

- 66%

mean number of working days lost

Control

6

5

4

3

2

1

0

PMBLCLBL

- 94.6%

number of patients requiring antibiotic treatment

9876543210

PMBLCLBL

No antibiotic use

1. B. Morandi et al. A mixture of bacterial mechanical lysates is more efficient than single strain lysate and of bacterial-derived soluble products for the induction of an activating phenotype in human dendritic cells, Immunology letters, 20112. E. Villa et al. May We Strengthen the Human Natural Defenses with Bacterial Lysates?, WAO journal, 3:S17-S23, 20103. F.Braido et al. Polyvalent mechanical bacterial lysate treatment in COPD : New immunological evidence, International Journal on Immunorehabilitation, vol. 13, no. 1, 20114. A.Macchi et al. Open comparative, randomized controlled clinical study of a new immunostimulating bacterial lysate in the prophylaxis of upper respiratory tract infections, ArzneimForschDrugRes 55, N°5, 276-281, 2005

CHEMICAL LYSIS (CLBL)

Amorphous substance: only soluble antigen

MECHANICAL LYSIS (PMBL)

Bacterial bodies’ clearly visible

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M

M

M

TCD4+

TCD4+

TCD4+

TCD4+

B B

B

B B BB

T

NK

NK

NK

PmBL is able to induce a potent maturation of dendritic cells which expressed CD 80, CD 83 and CD 86 markers1 2 3 4 5 6

mature dendritic cells are able to present antigen

PmBL is able to increase the reservoir of naïve B cells and early memory B cells to allow the immune system to be ready to fight infections3 7 8

PmBL is able to increase secretion of proinflammatory cytokines1 3 9

PmBL is able to increase the total number of natural Killer cells7

PmBL is able to increase CD 4 T helper cells 7 8 9

PmBL is able to recruit a larger number of precursor B cells to be differenciated in plasma cell7

PmBL is able to increase specific and opsonising immunoglobulins1 3 9 10

PmBL is able to induce efficient opsonization to allow the destruction of bacteria10

PMBL, Optimal immunogenic profile in clinical results4

PMBL, Unique process and formulation

POLYvALENt MECHANICAL BACtERIAL LYSAtE

1. B. Morandi et al. A mixture of bacterial mechanical lysates is more efficient than single strain lysate and of bacterial-derived soluble products for the induction of an activating phenotype in human dendritic cells, Immunology letters, 20112. Palmieri, et al. Prophylaxis of airways viral infections: role of the enhancement of the immune defenses, Giorn. It. Mal. Tor., 57, 1, 45-51, 20033. M. Pia Fuggetta et al. Attivazione delle risposte immunitarie mediante vaccini batterici, Eur. Respir. News, 15: 00-00 20074. E. Villa et al. May We Strengthen the Huma h Bacterial Lysates?, WAO journal, 3:S17-S23, 20105. F.Pregliasco et al. Control of acute respiratory infections. Stimulation of dendritic cells, Eur. J. Aerobiology and Aerotransmitted infections, vol.1, no. 1, 20046. G. Melioli et al. A polyvalent Mechanical bacterial lysate induces a powerful and specific immunoresponse in vivo by activating a cross-talk between innate and adaptative immunity, Clinical and Investigative Medicine, vol. 27, no. 4, 20047. F.Braido et al. Polyvalent mechanical bacterial lysate treatment in COPD : New immunological evidence, International Journal on Immunorehabilitation, vol. 13, no. 1, 20118. G. Lanzilli et al. In vivo effect of an immunostimulating bacterial lysate on human B lymphocytes, Int. J. Immunopathology and Pharmacology, vol. 19, no. 3, 551-559, 20069. G. Lanzilli et al. In vitro effects of an immunostimulating bacterial lysate on human lymphocyte function, Int. J. Immunopathology and Pharmacology, vol.18, no. 2, 245-254, 200510. G. Melioli, Opsonization : to eat or be eaten, Gior.It.Mal.Tor, 56, 4, 245-248, 2002

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PMBL, Proven clinical efficacyJournal Publication Title results (compared to control or placebo)

World Allergy Organization journal1

“May we strengthen the Human Natural Defenses with Bacterial Lysate”

Improvement of immunogenicity thanks to preservation of antigenic structure by mechanical lysis

PmBL stimulates both innate and specific immune response

European Journal of Aerobiology, environmental medicine and Air-borne infections2

“Evaluation of the clinical efficacy of a new polyvalent bacterial lysate obtained by mechanical lysis (PMBL) in a popupation of 180 school-aged children with recurrent respiratory infections”

reduction of mean number of infections by 53.6%

reduction of school absenteeism by 49.7%

Acta Bio Medica Ateneo Parmense3

“Strategies for optimizing compliance of paediatric patients for seasonal antibacterial vaccination with sublingually administered Polyvalent Mechanical Bacterial Lysates (PMBL)“

reduction of mean number of infections by 29.5%

Increase of B lymphocytes by 67.8%

GIMMOC4 “Immunoprophylaxis of recurring bacterial infections of respiratory tracts in paediatric age: clinical experience through a new immunostimulating vaccine”

higher proportion of healthy children (no respiratory infections) with PmBL: 67.5%

reduction of complementary medicine use (antibiotics/antipyretics/antiphlogistics) by 66.7%

ArzneimForschDrugRes5 “Prevention of Reccurent Upper Respiratory tract infections in a community of cloistered Nuns using a new immunostimulating Bacterial lysate”

reduction of the number of infections by 77.4% after treatment and by 81.2% after 3 months follow-up

Increase of secretory IgA by 110%

Trends in Medicine6 “A new bacterial lysate protects by reducing infectious exacerbations in moderate to very severe COPD”

reduction of episodes of acute exacerbations/patient by 20.7%

reduction of the hospitalization rate by 44.6%

Gior It Mal Tor7 “Prophylaxis of episodes of winter airway infections with a sublingual antibacterial vaccine obtained by mechanical lysis, PMBL (Ismigen-Zambon): clinical trial in patients with a case history of tuberculosis”

reduction of bronchial infections by 63.4%

reduction of antibiotic use by 50.6%

PMBL Key advantages Higher immunogenic profile (mechanical lysis, sublingual route, acts on the whole immune cascade) Stimulation of both innate and specific immune response > Dual action on prevention of viral and bacterial Respiratory Tract Infections Significant reduction of number of upper and lower respiratory infections Significant reduction of antibiotics use

Easy posology scheme 10 days/month during 3 months

1 2 3 4 5 6 78 9 10 11 12 13 14

15 16 17 18 19 20 2122 23 24 25 26 27 2829 30 31

1. E. Villa et al. May We Strengthen the Human Natural Defenses with Bacterial Lysates?, WAO journal, 3:S17-S23, 20102. O. T. Aksic et al. Evaluation of the clinical efficacy of a new polyvalent bacterial lysate obtained by mechanical lysis (PMBL) in a popupation of 180 school-aged children with recurrent respiratory infections, European Journal of Aerobiology, environmental medicine and Air-borne infections, vol1, no. 1, 20053. F. Rosaschino et al. Strategies for optimizing compliance of paediatric patients for seasonal antibacterial vaccination with sublingually administered Polyvalent Mechanical Bacterial Lysates (PMBL), Acta Bio Medica Ateneo Parmense, 75, 171-178, 20044. I. La Mantia et al. Immunoprophylaxis of recurring bacterial infections of respiratory tracts in paediatric age: clinical experience through a new immunostimulating vaccine, GIMMOC, Vol. XI, N° 3, p. 147 - 155, 20075. D. Tricarico et al. Preventi on of Reccurent Upper Respiratory tract infections in a community of cloistered Nunsusing a new immunostimulating Bacterial lysate, ArzneimForschDrugRes 54, no. 1, 57-63, 20046. M.Cazzola, A new bacterial lysate protects by reducing infectious exacerbations in moderate to very severe COPD, Trends in Medicine, 20067. V. M. Boris, Prophylaxis of episodes of winter airway infections with a sublingual antibacterial vaccine obtained by mechanical lysis, PMBL (Ismigen-Zambon): clinical trial in patients with a case history of tuberculosis, Gior It Mal Tor, 57, 3, 2003

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www.LALLEmAnDPhArmA.COm

Tel. +41 (0)91 980 46 13 Fax +41 (0)91 980 46 15

PMBL Worldwide presence

LaLLemand Pharma aG Piazza molino nuovo 17

6900 LUGanO - Switzerland

LaLLemand Pharma InTernaTIOnaL Bahnhofstrasse 7

6301 ZUG - Switzerland

LaLLemand Pharma eUrOPe Toftebakken 9B

3460 BIrKerØd - denmark

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