Institute for Immunology and Informatics ( iCubed )

1. Institute for Immunology and Informatics (iCubed) URI Biotechnology Program in Providence The College of the Environment and Life Sciences University of Rhode Island www.immunome.org URI Alumni Board 2012 D. Spero icubed overview 2011

2. GAIA Vaccine Foundation Project West Africa (Bamako, Mali) http://www.GAIAVaccine.org

3. Institute for Immunology and Informatics (iCubed) Our Mission: To design safer, efficacious vaccines and therapeutics to prevent and cure human and animal disease using novel computer-based (informatics) immunology tools Focus: Accelerated vaccine discovery for infectious diseases and biodefense D. Spero URI Alumni Board 2012

4. The iCubed Leadership • Annie De Groot, M.D. • Research Professor and Director iCubed • CEO EpiVax Inc. • Expertise: Immunology, Immunoinformatics, • Vaccine Research, Infectious Diseases, • Autoimmunity, Biotechnology • DeniceSpero, Ph.D. • Research Professor and Co-director iCubed • Former President of Developing World Cures, Inc. • Vice President Drug Discovery BoehringerIngelheim Pharmaceuticals, Inc. • Pharmaceutical Leader, Experienced Drug Developer • Expertise: Drug metabolism and pharmacokinetics, Drug Safety, Drug Formulation, Organic Chemistry, Autoimmune Diseases, Developing world diseases, Pharmaceutical industry

5. Why Are Vaccines so Important? • Vaccines are the single most cost effective means • of controlling the spread of infectious disease • No public health tool has improved global health more than vaccines D. Spero URI Alumni Board 2012

6. The Goal- Prevent Disease

7. Why are Vaccines a Hot Commodity ? After years of beating a retreat from making vaccines, the world's biggest drug companies are piling back in. Vaccines are giving the drug business a shot in the arm. . . .For example, Johnson & Johnson paid $441 million for a stake in Crucell, a Dutch vaccine firm, and . . . . . . just last week, Roche snatched up Illumina for $5.7B. Through the deal, Roche would pick up technology to read the genetic makeup of tumors, boosting the potential for targeted personalized medicine in this area, as Bloomberg notes. What are some of those medicines? Well, of course, Vaccines.

8. The Focus: Better, Faster Vaccines The Evolution of Vaccines Better understanding of vaccine MOA Improve vaccine safety and efficacy Vaccines are evolving rapidly Can we make them even Accelerate Vaccine Design Faster – Safer – Better?

9. “Old Style” Vaccines Shake . . . and bake – That was then

10. How the Flu Vaccine is made Sanofi Pasteur 50 year old technology, growing influenza virus in chicken embryos- doesn’t work with avian flu.

11. Accelerating Drivers • Molecular biology • High throughput sequencing • Genomics / proteomics • Bioinformatics • Computational power

12. From Genome to Vaccine Accelerating Vaccine Design

13. Vaccine Design Tools and Techniques http://www.epivax.com/platform iVAXToolkit

14. Strain 1 Comparative Genomics Impacts Vaccine Immunogen Selection Comparative Genomics dispensable genes Strain 3 Strain 2 core genome pangenome strain-specific genes

15. Safer: remove conserved epitopes Potentially detrimental cross-reactive epitopes Potentially detrimental cross-reactive epitopes Protective epitopes

16. CTRPNNTRK CTRPNNTRK CTRPNNTRK CTRPNNTRK CTRPNNTRK CTRPNNTRK Conserved Epitope-allows protection vs. more strains w/ fewer epitopes. CTRPNNTRK Overcome Strain Variation- Conservatrix Conservatrix: Overcome the Challenge of Variability HIV HCV Influenza

17. Epitopes Conserved over Time & Space August 25, 2011 Confidential

18. Making the Vaccine Intended Protein Product: Many epitopes strung together in a “String-of-Beads” Reverse Translation: Determines the DNA sequence necessary to code for the intended protein. This DNA is assembled for insertion into an expression vector. DNA insert Protein product (folded) DNA Vector

19. Other Formulations Vaccine Formulations DNA – chain of epitopes, or peptide in liposomes ICS-optimized whole proteins ICS-optimized proteins in VLP

20. iVAX Toolkit On Line Access IVAX Toolkit: In use by Researchers funded by the NIH Cooperative Centers for Human Immunology CCHI

21. Protozoan Infections African Trypanosomiasis Chagas Disease Leishmaniasis Bacterial & Viral Infections Buruli Ulcer Dengue Leprosy Trachoma** Helminth (Worm) Infections Soil-Transmitted Helminth Infections Ascariasis** Hookworm** Trichuriasis** Schistsosomiasis** Lymphatic Filariasis** Onchocerciasis** Dracunculiasis iVAX – for Neglected Tropical Diseases **indicates one of “The Big Seven”NTDs

22. Neglected Tropical Diseases

23. Leading Causes of Life-Years Lost to Disability and Premature Death

24. $0.62 Global Burden of Infectious Disease DALYs Funding Per DALY 91.4 million 84.5 million 67.3 million 62.0 million 58.6 million 56.6 million 49.2 million 46.5 million 38.7 million 34.7 million

25. Epitope Discovery Epitope Validation Epitope Discovery Epitope Validation Epitope Discovery Epitope Validation Epitope Validation Epitope Discovery Epitope Validation Construct Design Epitope Validation Epitope Discovery Epitope Discovery Current Vaccine Design Pipeline Burk/Tuly/MP Immuno-genicity Animal Model Validation Construct Design Immuno-genicity Animal Model Validation HIV/TB Construct Design Immuno-genicity Animal Model Validation Tularemia Construct Design Animal Model Validation Monkeypox Immuno-genicity H. pylori Construct Design Animal Model Validation Immuno-genicity Construct Design Animal Model Validation VEE/Wee Immuno-genicity

26. Immunome-DerivedMonkeypoxVaccine: VennVax smallpox vaccinia Immunogenic Epitopes Shared Immunogenic Epitopes Vaccine

27. Prime-Boost Immunization with VennVax Sacrifice 3 mice Week 16 Immunization Week 8-10 1. epitope DNA vaccine prime 2. epitope peptide boost Aerosol challenge IFN-g multiplex ELISA 1. control DNA prime 2. control peptide boost

28. Survival of VennVax-Vaccinated Mice After Aerosol Challenge 100% survival of Vaccinated mice vs. 17%of placebo 0 20 40 60 80 100 Moise et al. Vaccine. 2011; 29:501-11

29. Week 0 H. pylori SS1 H. pylori SS1 lysate IN H. pylori SS1 H. pylori SS1 H. pylori SS1 Therapeutic H. pylori Vaccination Week 6 Week 12-19 Week 51 1. epitope DNA vaccine prime IN 2. epitope peptide boost IN IFN-gamma and IL-4 ELISpot 1. epitope DNA vaccine prime IM 2. epitope peptide boost IN Histology 1. control DNA prime IN 2. control peptide boost IN

30. *** P<0.001 ** P<0.01 *** P<0.001 HelicoVax Eradicates H. pylori Infection This result accomplished in just over 24 months . . . Moss et al, Vaccine 2011;29:2085-91

31. Next Step in Vaccine Evolution?

32. And . . . . PigMatrix FishMatrix

33. “That was then”: How the Flu Vaccine is made Sanofi Pasteur 50 year old technology, growing influenza virus in chicken embryos

34. This is Now!The iCubed “Gene to Vaccine” Approach Genome of the pathogen Select pathogen proteins Select peptides that will interact with the human immune system String peptides together to make a vaccine No whole viruses or bacteria: Fast and targeted!

35. Faster! The “Gene to Vaccine” – 60 days Pathogen Genome(s) Genome-Derived Vaccine Components Funding from DARPA for this approach to be announced this week!

36. A bold statement: • Personalized vaccines will be a reality in 10 to 15 years. • How so? Because the technology that can design safe, effective vaccines already exists, right here at URI. • Moving vaccine development from 20 years to 20 minutes is the next step. • What is needed ? • Vision. Leadership. Financial and Infrastructure Support. • “Yes we can!” We are able to make better, safer and faster vaccines, and also develop a workforce that is prepared to bring that dream to fruition.

37. New Challenges/ New Opportunities • Emerging Infectious Disease Threats • Unprecedented infectious disease threats (population density, global travel, global warming, widespread bioengineering technology and capabilities) • Advances in genomics, microbiology and immunology create an opportunity to re-think current processes

38. How are we meeting the challenge? iCubed Research Areas Applying New Tools to Design New, Safer and Faster Vaccines: • Biodefense- defending our military and our communities • Infectious diseases - Hepatitis C, H. pylori, emerging ID • Cancer - New collaborations with cancer experts • Tropical Diseases -Developing world and Southern US • FarmVax- Fish, swine, chickens to protect our food, protein sources

39. Providing students with the right skill set • Immunology • Vaccinology • Protein Manufacturing • Entrepreneurship • Neglected Tropical Disease Training • Vaccine Renaissance Conference

40. The Business Side of iCubed • Vision: To Build URI as the Major Center for Next Generation Vaccine Discovery in the World • Entrepreneurial Model • Primarily self-funded through grants and overhead return • Seeking Private Funding to: • Expand research projects • Support faculty and laboratory space

41. iCubedTrajectory • Opened 2008 – 3 full time staff, several part time faculty • As of 2012 - 15 scientists and staff • Many Collaborations: Brown/Lifespan, Dartmouth, UConn, NIH (LPD) USDA (ARS), DoD, Peru (Cayetano Heredia), Thailand, Indonesia (Eijkman Institute) • Awarded grants since inception: $11.3 M dollars

42. Institute for Immunology and InformaticsLifespan, URI, EpiVax 2009 Translational Research on Immunome-Derived Accelerated Vaccines Projects at the Institute for Immunology and Informatics In collaboration with EpiVax

43. The iCubed Team