1. 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

2. The New Campaign

4. 4. Marketing 3. Product Development 1. Meeting an unmet need 2. “Cahiers Des Charges” Must place market needs as the focal point “as articulated by the customer.” Customer Centric Attributes Features Performance “I need a moisturizer that is better than the leading brand” Establishing the product blueprint Outcome Driven Brand Plan The Otx Sales Process Meeting Product Guidelines Innovative formulation Novel vehicles Clinical assessment Commercialization

5. None Neutro. elastase Ela2 19p13.3 AD German, English, French, N. Am. Cryopirin CIAS1 1q44 AD Dutch French Mevalonate kinase 12q24 AR Scottish, Irish TNFR type 1 TNFRSF1A 12p13 AD Jewish, Turkish, Arab, Armenian Pyrin Marenostrin MEFV 16p13 AR Ancest Protein Gene Chrom Inherit CH MWS/FCU HIDSTRAPSFMF Familial Periodic Fever Syndromes

6. Data from Children’s Defense Fund. CDF Publications 1998 CCC = Child care center CCH = Family CCC Distribution of Child Care US

7. Rare Tlr 4 Mutations Are Associated With 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.

8. West Nile Virus (WNV) http://www.dierentuin.net/pictures/huismuis.jpg anatomy.ucsf.edu/Pages/mouseclub/mousejournalclub.html wildlife.usask.ca/WestNileAlertHTML/viron.jpg

9. 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.

10. WNV 20% symptomatic 1/150 with meningitis or encephalitis Relevance to Humans? 20% symptomatic 1/150 with meningitis or encephalitis

11. 600 potential vaccine candidates identified 350 proteins expressed in E. coli 344 proteins used to immunize mice 355 sera tested 91 novel surface-exposed proteins identified 29 novel proteins induce bactericidal activity 5 vaccine candidates 18 months 24 months Scale-up GMP / IND 1 year Men B Vaccine: A Genomic Approach Clinical trial

12. Alefacept 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 1–12 Dosing Weeks 13–24 Follow-up 24681012141618202224 Primary Efficacy End Point IV = 14% IM = 21% First Course IV = 25% IM = 28% PASI 75 Responders Posttreatment Response Rate IV = 11% IM = 7% + Phase 3 Efficacy Results

13. 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?

14. Binding sites for both macrolides & telithromycin Mechanism of Action Domain II Domain V Telithromycin binds 10X more strongly than macrolides because of its better domain II contact Site of methylation Douthwait et al Mol Micro 36:183, 2000