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Binax NOW RTI Products

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2WHO comments:

More than any other infectious disease, pneumonia remains the number one killer worldwide.

Streptococcus pneumoniae and Haemophilus influenzaeare the top two bacterial causes of acute respiratory infections.

Both viral and bacteria respiratory infections present the same clinical symptoms and can often only be distinguished by laboratory tests

80% of pneumonia patients may unnecessarily be given antibiotics - contributing to antibiotic resistance

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3Case Review Respiratory Tract Infection (RTI) cases

very large cases several diseases with similar symptoms

Target cases Community-acquired pneumonia Nosocomial pneumonia cases Acute Flu-like cases

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4Community - Acquired Pneumonia

~12 million cases treated annually worldwide

S. pneumoniae is the leading cause ofbacterial pneumonia -up to 65% of cases in some studies

Legionella also a leading cause of community-acquired pneumonia - up to 15%

S. pneumoniae and Legionella pneumonia have high mortality rates - as high as 30%

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5Acute Flu-like Cases Clinical symptoms of lower RTI diseases

(pneumonia, acute influenza and acute bronchitis) similar

Bacterial pneumonia can be a complication of acute influenza or acute bronchitis

Significantly increases overall case potential

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6Disease Overview

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7Causative Agents of Community-Acquired Pneumonia

Bacterial Viral

Streptococcus pneumoniae Influenza A & B

Legionella pneumohila RSV

Haemophilus influenza type B Adenovirus

Non typable Haemophilus Para Influenza

Staphlococcus aureus

Moraxella catarrhalis

Pseudomonas aeruginosa

Chlymydia pneumonia

Mycoplasma pneumonia 7

8Community-Acquired PneumoniaCAP

S. pneumoniae is the leading cause of bacterial pneumonia and CAP - up to 65% of all cases in some studies

Legionella also a leading cause of community-acquired pneumonia - up to 15%

S. pneumoniae and Legionella pneumonia have high mortality rates - as high as 30%

Bacterial infections can occur as a complication of influenza

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9Community-Acquired Pneumonia

Transmission: person to person by direct contact with infectious secretions

Risk groups elderly children under 2 and /

or attending day care patients with

underlying illness immunocompromised

patients

Symptoms fever, chills chest pain, pleurisy,

difficulty breathing blood-tinged sputum headache cough (often non-

productive)

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Community-Acquired Pneumonia

Treatment Pathogen-specific diagnosis -

help direct the most cost-effective treatment minimizes the risk of increasing antibiotic resistance

Empirical treatment may not always be the most cost-effective treatment increases the risk of antibiotic resistance

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Community-Acquired Pneumonia

many strains of S. pneumoniae have intermediate sensitivity and resistance to penicillin and resistance to single or multiple broad-spectrum antibiotics (Goldstein and Acar, 1996)

accurate diagnosis required allowing specificantibiotic therapy

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Diagnostics

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Diagnostics

Blood Culture

Sputum Culture

Sputum Gram Stain

PCR / DFA

NOW ICT Urinary Antigen Test

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Diagnostics Blood Culture

Advantages positive = confirmation patient is bacteremic allows for drug susceptibility testing

Disadvantages only 10-30% of all pneumonia cases are

bacteremic - positive culture result in only 25% of cases (Musher, 1992)

potential errors by technician

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Diagnostics Blood Culture

Disadvantages can also be positive in patients with meningitis,

otitis media, septic arthritis, etc 24-48 hours incubation requires experienced technicians to perform and

interpret results expensive

technician time instrumentation (incubators)

invasive for the patient

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Diagnostics Sputum Culture

Advantages supplies and reagents relatively inexpensive non-invasive for the patient allows for drug susceptibility testing

Disadvantages samples must be taken prior to antibiotic therapy sample required from lower respiratory tract;

difficult to obtain (non-productive cough, children, elderly)

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Diagnostics Sputum Culture

Disadvantages samples must be processed immediately

delays reduce isolation rates of the organism high false positive rates (carrier) low sensitivity and specificity

normally 48 hours for positive identification

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Diagnostics Sputum Culture

Disadvantages expensive

technician time equipment experienced personnel are needed to perform and

interpret results

Difficult to identify infecting organism

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Diagnostics Sputum Gram Stain

Advantages inexpensive reagents and supplies non-invasive for the patient rapid test time

Disadvantages requires sample from lower respiratory tract;

difficult to obtain samples must be processed immediately

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Diagnostics Sputum Gram Stain

Disadvantages high false positive rate low sensitivity and specificity; large numbers of

organisms must be present does not allow for drug susceptibility testing requires experienced personnel

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Diagnostics PCR / DFA

Advantages same day results specificity

Disadvantages requires sample from lower respiratory tract;

difficult to obtain expensive - equipment, skilled technician sensitivity

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Diagnostics NOW ICT Urinary Antigen

Technology detects antigen, which is a common component of

the cell wall within the species S. pneumoniae - C-polysaccharide antigen, common to

all serotypes within the species Legionella - lipopolysaccharide portion of the serogroup

1 cell wall rabbit anti-species antibody as capture component rabbit anti-species antibody conjugated to colloidal

gold as detection component

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Technology

Absorbent Control Line--Goat

anti-rabbit IgG Sample Line--Rabbit

anti-S. pneumoniaeantibody

Conjugate Pad Sample Pad ( patent No. 91/214051).

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Intellectual Property 12 Issued Patents

4 ICT platform 7 Magnetic particles 1 Meningitis test

11 Patents Applied For respiratory, meningitis, and bacteria screen area

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Diagnostics NOW ICT Urinary Antigen

Advantages rapid results - 15 minutes non-invasive sample - urine easy test to run and interpret results accurate

Limitations Susceptibility cannot be performed Single bacteria test

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Diagnostics NOW ICT Urinary Antigen

Performance Data S. pneumoniae

Sensitivity 86% Specificity 94%

Legionella Sensitivity 95% Specificity 95%

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Comparison of Streptococcus pneumoniae Test Methods

Methods Sample Type Sensitivity Specificity Time

Binax NOW Urine 86%1 94% 1 15 mins

PCR Blood 52% 100% 4 hrs

Blood Culture Blood 10-30% 2 >95% 48 hrs

Sputum Culture Sputum 50-60% 50-80% 48 hrs

Sputum Gram Stain Sputum 50-60% 50-80% 15 mins

Diagnostics

1-Retrospective study data -- blood culture used as reference method.2-Numbers reflect percent of pneumonia patient population estimated to be bacteremic.

Note: Sensitivity and specificity data on blood culture, sputum culture, and sputum Gram stain taken from variouspublished studies. References available upon request.

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NOW ICT Features Easy to run Rapid test - only 15 minute tests for

S. pneumoniae and Legionella available Uses non-invasive sample No special equipment needed Easy to interpret resul

Positioning

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Accurate results U.S. FDA cleared products Multiple applications for S. pneumoniae

test - pneumonia, CSF and otitis media

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NOW ICT S. pneumoniaeadditional applications

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CSF application

Anti-microbial therapy often initiated empirically because causative agent not identified in advance

Sensitivity of CSF gram staining is 75% - decreases to 50% in patients given anti-microbial therapy

Latex bacterial antigen assays have low sensitivity in CSF Streptococcus pneumoniae is typically the second most

common causative agent of community-acquired acute bacterial meningitis

Increasing rates of pneumococcal resistance to penicillin and third generation cephalosporins

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CSF application

NOW ICT S. pneumoniae test 100% sensitivity and specificity with CSF sample published studies

New Rapid Antigen Test for Diagnosis of PneumococcalMeningitis.Marcos et al, The Lancet 357: 1499-1500, 2001.

Using the NOW test in Cerebrospinal Fluid for the Rapid Diagnosis of Pneumococcal meningitis.Samrai et al, ASM: 114, 2001.

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CSF application

NOW ICT S. pneumoniae test additional application to support bringing the test into a

hospital lab only accurate rapid test for detection of a critical

pathogen for bacterial meningitis

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Otitis Media application

NOW ICT S. pneumoniae test Rapid Detection of S. pneumoniae in the Airways of Children

with Acute Otitis Media.Faden et al, ASM: 113, 2001.

Sensitivity 90.0% (18/20) versus culture positive nasopharangeal samples

Specificity 86.9% (21/23) versus culture negative nasopharangeal samples

one of three leading causes of otitis media

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Published Studies - S. pneumoniae Evaluation of a Rapid Immunochromatographic Test for the

Detection of Streptococcus pneumoniae Antigen in Urine Samples from Adults with Community-Acquired Pneumonia

Murdoch et al, ASM: 112, 2001 Detection of Streptococcus pneumoniae Antigen by a Rapid

Immunochromatographic Assay in Urine Specimens Dominguez et al: Chest, 119: 243-249, 2001

Diagnostic Utility of a Rapid Urine Pneumococcal Antigen Assay

Neuman et al, 2001 Pediatric Academic Societies Meeting

Reference

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Published Studies - S. pneumoniae Evaluation of Binax NOW, an Assay for the Detection of

Pneumococcal Antigen in Urine Samples, Performed among Pediatric Patients

Dowell et al, Clinical Infectious Diseases, 32: 2001 New Rapid Test for Detecting S. pneumoniae in Lower

Respiratory Tract InfectionsLienhard et al, Clinical Microbiology and Infection 7: 101

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Detection of Streptococcus pneumoniae Antigen by a Rapid Immunochromatogrphic Assay in Urine Samples

CHEST, 119: 243-249, 2001J.Dominguez et al

Detection of Streptococcus pneumoniae Antigen by a Rapid Immunochromatogrphic Assay in Urine Samples

CHEST, 119: 243-249, 2001J.Dominguez et al

Conclusions(1) Now S. pneumoniae test is sensitive and specific(2) Now S. pneumoniae test is a valuable tool for diagnosing

pneumococcal pneumonia cases, especially nonbacteremic cases, which are often not diagnosed.

(3) Blood culture is only useful in approximately 25% of pneumococcal pneumonia cases (i.e. that is the percent of the population that is bacteremic).

(4) Sputum cultures only provide a probable diagnosis due to difficulties associated with methodology (obtaining reliable samples, etc.) and samples for culture are rarely taken invasively due to concerns with the techniques that must be used.

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Evaluation of a Rapid Immunochromatographic Test for the Detection of Streptococcus pneumoniae Antigen

in Urine Samples from Adults with Community-Acquired Pneumonia

ASM: 112, 2001 Murdoch et al,

Evaluation of a Rapid Immunochromatographic Test for the Detection of Streptococcus pneumoniae Antigen

in Urine Samples from Adults with Community-Acquired Pneumonia

ASM: 112, 2001 Murdoch et al,

The authors conclude : The Now S. pneumoniae antigen test is a useful

adjunct to culture for determining the etiology of community-acquired pneumonia in adults.

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90.01.05

Immuno-Chromatographic Test v.s. Latex Agglutination Test

108 CFU/ml* Positive 108 CFU/ml Positive

107 CFU/ml Positive 107 CFU/ml Negative

106 CFU/ml Positive 106 CFU/ml Negative

105 CFU/ml Positive (weak) 105 CFU/ml Negative

104 CFU/ml Negative 104 CFU/ml Negative

Now Wellcogen

* Adjust cell suspension of S. pneumoniae to 0.5 McFarland ( 108 CFU/ml )

Binax NOW RTI ProductsCase ReviewCommunity - Acquired PneumoniaAcute Flu-like CasesDisease OverviewCausative Agents of Community-Acquired PneumoniaCommunity-Acquired PneumoniaCAPCommunity-Acquired PneumoniaCommunity-Acquired PneumoniaCommunity-Acquired PneumoniaDiagnosticsDiagnosticsDiagnosticsDiagnosticsDiagnosticsDiagnosticsDiagnosticsDiagnosticsDiagnosticsDiagnosticsDiagnosticsTechnologyIntellectual PropertyDiagnosticsDiagnosticsComparison of Streptococcus pneumoniae Test MethodsPositioningNOW ICT S. pneumoniae additional applicationsCSF applicationCSF applicationCSF applicationOtitis Media application