Epidemic-Curve Graph (Top) and Field Position Diagram (Bottom) of Cases of MRSA Infection among St. Louis Rams Football Players in 2003

Epidemic-Curve Graph (Top) and Field Position Diagram (Bottom) of Cases of MRSA Infection among St. Louis Rams Football Players in 2003

Kazakova, S. V. et al. N Engl J Med 2005;352:468-475

The New CampaignThe New Campaign

The New CampaignThe New Campaign

4. Marketing4. Marketing

3. Product Development3. Product Development

1. Meeting an unmet need1. Meeting an unmet need 2. “Cahiers Des Charges”2. “Cahiers Des Charges”

• Must place market needs as the focal point• “as articulated by the customer.”

Customer CentricCustomer Centric

• Attributes• Features• Performance• “I need a moisturizer that is

better than the leading brand”

Establishing the productEstablishing the productblueprintblueprint

Outcome DrivenOutcome Driven

Brand PlanBrand Plan

The Otx Sales ProcessThe Otx Sales Process

Meeting Product GuidelinesMeeting Product Guidelines

• Innovative formulation• Novel vehicles• Clinical assessment• Commercialization

None

Neutro.elastase

Ela2

19p13.3

AD

German, English, French,N. Am.

Cryopirin

CIAS1

1q44

AD

Dutch French

Mevalonatekinase

Mevalonatekinase

12q24

AR

Scottish,Irish

TNFR type 1

TNFRSF1A

12p13

AD

Jewish,Turkish, Arab,Armenian

PyrinMarenostrin

MEFV

16p13

AR

Ancest

Protein

Gene

Chrom

Inherit

CHMWS/FCUHIDSTRAPSFMF

Familial Periodic Fever SyndromesFamilial Periodic Fever Syndromes

ParentsRelativesCCCCCHIn-home Care

Data from Children’s Defense Fund. CDF Publications 1998

CCC = Child care centerCCH = Family CCC

Distribution of Child Care USDistribution of Child Care US

Rare Tlr 4 Mutations Are AssociatedWith Meningococcal Susceptibility

~7.5% meningococcal sepsis can be attributed to rare mutations at TLR4 locus

Smirnova I, et al. Proc Natl Acad Sci USA. 2003;100:6075-6080.

West Nile Virus (WNV)

http://www.dierentuin.net/pictures/huismuis.jpghttp://www.dierentuin.net/pictures/huismuis.jpg

anatomy.ucsf.edu/Pages/mouseclub/mousejournalclub.htmlanatomy.ucsf.edu/Pages/mouseclub/mousejournalclub.html

wildlife.usask.ca/WestNileAlertHTML/viron.jpgwildlife.usask.ca/WestNileAlertHTML/viron.jpg

A stop codon in exon 4 of the interferon response gene, 2’-5’-oligoadenylate synthetase/L1 isoform (Oas1) may be responsible for susceptibility to WNV and other flaviviruses

Perelygin AA, et al. Proc Natl Acad Sci USA. 2002;99:9322-9327.Mashimo T, et al. Proc Natl Acad Sci USA. 2002;99:11311-11316.

WNV

20% symptomatic 1/150 with meningitis or encephalitis

Relevance to Humans?Relevance to Humans?

20% symptomatic 1/150 with meningitis or encephalitis

• 600 potential vaccine candidates identified

• 350 proteins expressed in E. coli

• 344 proteins used to immunize mice

• 355 sera tested

• 91 novel surface-exposedproteins identified

• 29 novel proteins induce

bactericidal activity

5 vaccinecandidate

s

18 months

24 months

Scale-upGMP / IND

1 year

Men B Vaccine: A Genomic ApproachMen B Vaccine: A Genomic Approach

Clinical trialClinical trial

Alefacept in PsoriasisAlefacept in Psoriasis

Krueger GG, et al. J Amer Acad Dermatol. 2002;47:821-833; Lebwohl M, et al. Arch Dermatol. 2003;139:719-727.

Weeks

Placebo

Alefacept 7.5 mg

Weeks 1–12Dosing

Weeks 13–24Follow-up

2 4 6 8 10 12 14 16 18 20 22 24

Primary EfficacyEnd Point

IV = 14%IV = 14%IM = 21%IM = 21%First CourseFirst Course IV = 25%IV = 25%

IM = 28%IM = 28%

PASI 75 Responders

PosttreatmentResponse Rate

IV = 11%IV = 11%IM = 7%IM = 7%+

Phase 3 Efficacy Results

Wunderink, R. G. et al. Chest 2003;124:1789-1797

Clinical cure rates for linezolid and vancomycin therapy in patients with Gram-positive, nosocomial pneumonia

Linezolid for MRSA pneumonia?Linezolid for MRSA pneumonia?

Binding sites for both macrolides & telithromycin

Mechanism of Mechanism of ActionAction

Domain IIDomain II Domain VDomain V

Telithromycinbinds 10X more strongly than macrolidesbecause of its better domain II contact

Site ofmethylation

Douthwait et al Mol Micro 36:183, 2000Douthwait et al Mol Micro 36:183, 2000