1. New Rectal Microbicide Formulations Ian McGowan MD PhD FRCP University of Pittsburgh

2. The HIV Prevention Landscape
Safer sex including condoms
Drug resistant GC, syphilis, HSV, HPV, and HCV, invasive meningococcal disease
Oral PrEP
In development
Rectal microbicides
Long-acting antiretroviral PrEP
HIV vaccine
Broadly neutralizing antibody PrEP

3. New Molecules Population Council CHARM Program
MIV-150, carrageenan, Zinc acetate
CHARM Program
Maraviroc gel
University of Louisville / Intrucept
Griffithsin gel
Johns Hopkins University
Enema formulations of tenofovir analogues

4. Griffithsin Gel

5. Griffithsin Gel
Originally isolated from red algae found off the coast of New Zealand
Produced in tobacco plants
Active against HIV, HSV, and HCV
Being developed as a rectal microbicide

6. PREVENT U19 Program Pre-exposure prevention of viral entry
Development of a GRFT gel
Evaluation in the macaque model
Evaluation in a Phase 1 study
Safety
Acceptability
PK & PD

7. PREVENT U19 Timeline

8. Tenofovir Prodrug Enemas

9. Douching is a Common Practice

10. Enema Coverage

11. Mucosal Contact

12. PK Profile of Enema Formulations

13. DREAM U19 Program Pre-clinical (mice and macaques) Clinical
Selection of saline formulation
Selection of optimal TFV prodrug
Compare TFV with TFV analog prodrug
Clinical
DREAM-01: TFV enema dose escalation
DREAM-02: Enema ± sex & product distribution
DREAM-03: Optimized TFV versus TFV prodrug

14. DREAM U19 Timeline 2015 2016 2017 2018 2019 Preclinical X IND
Formulation
DREAM-01
DREAM-02
DREAM-03

15. Acknowledgements
The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health.

16. Thank You