Copernicus: Delivering the Promise of Nucleic Acid Therapeutics

1. Copernicus:Delivering the Promise of Nucleic Acid Therapeutics Robert C. Moen, M.D., Ph.D. President & CEO rmoen@cgsys.com

2. Copernicus Therapeutics, Inc. • A leader in the emerging field of nucleic acid delivery and therapeutics (12 issued patents, more pending) • Enable first in class therapeutic molecules employing DNA, RNA, siRNA • Address unmet medical needs • Cystic fibrosis • Viral lung diseases (influenza, avian flu, SARS) • Eye disorders (macular degeneration, retinitis pigmentosa) • Established proof-of-concept in humans (CF trial)

3. The Copernicus Platform Technology:Nucleic Acid Nanoparticles • DNA (or RNA/siRNA) Compaction • Single molecules of NA condensed with amino acids • Simple, reproducible manufacturing process • cGMP grade raw materials available (final assembly) • Stable (>3 years at 4°C, > 9 months room temp) • Stable at clinically relevant concentrations • IP covers composition of matter, methods and uses

4. Advantages of Copernicus Technology • Non-toxic • Non-immunogenic • Repetitive dosing possible • Drug does NOT alter human genomic DNA, but introduces nucleic acids into the cell • Highly efficient delivery to cells • Both dividing AND non-dividing cells

5. Uptake and Trafficking of Nanoparticles nucleolus nuclear pore NON-DEGRADATIVE TRAFFICKING PATHWAY Released nucleic acid BINDING TO CELL SURFACE NUCLEOLIN COMPLEX Nanoparticle nucleolin In collaboration with D. Kube and P. Davis, CWRU

6. Why a Cystic Fibrosis Focus? • Mutations in a single gene (CFTR) cause CF, only ~5% of lung cells need to be corrected, a wide range of expression is therapeutic and nontoxic Single gene Models • Copernicus treatment successful in CF animal model • Accelerated approval process & orphan drug status FDA • Cystic Fibrosis Foundation and State of Ohio TAF support. Support • No existing corrective treatments, only symptomatic therapy with limited effectiveness • Provides proof of concept yet large market size Treatments Market

7. Cystic Fibrosis Clinical Trial has Provided Proof of Principle • Formulation well-tolerated and safe • Strong gene transfer endpoints • Efficient DNA uptake into target cells • Correction of the CFTR chloride channel defect Konstan MW et al, “Single Dose Escalation Study to Evaluate Safety of Nasal Administration of CFTR001 Gene Transfer Vector to Subjects with Cystic Fibrosis”, Human Gene Therapy, 15:1255-69, 2004.

8. Platform Technology Addresses Multiple Indications With Significant Markets • DNA and/or siRNA • Aerosol delivery • Cystic Fibrosis • Influenza • RSV, SARs, Bird flu, BioWarfare • Eye (retina) • Macular degeneration (> 5 million pts in US) • Retinitis pigmentosa (~ 70,000 pts in US) • Diabetic retinopathy (~ 900,000 pts in US with severe disease) • Others (neural, neovasculature, tumors)

9. Influenza A Mouse ModelCompacted siRNA Therapy NP and AP conserved across all strains of Influenza A, not flu season specific ! Fisher’s exact test p2 = 0.028 Dosing of compacted siRNA followed by influenza A virus

10. Subretinal Injection of DNA Nanoparticles Encoding EGFP IHC DETECTION nearly 100% gene transfer of rods and cones in the retina OUTER NUCLEAR LAYER (nuclei of rods and cones) INNER NUCLEAR LAYER (nuclei of second order neurons) Results 10-20 times better than seen with any other system

11. Direct Brain Gene Transfer • Comparable to best results for viral vectors (lentivirus, AAV) • Viral vectors have toxicities related to immunity • No inflammation or immune response to DNA nanoparticles • Partnering opportunities for large markets with unmet medical needs (e.g. Parkinson’s disease) • Efficient transfer into neural stem cells in vitro

12. Cystic Fibrosis Influenza, etc. Retinitis Pigmentosa Macular Degeneration Parkinson’s Disease Product Summary Clinical Pre-Clinical Development I II III

13. Management • Robert C. Moen, M.D., Ph.D.(CEO and President) • VP of Clinical and Regulatory Affairs at Baxter Healthcare • VP of Clinical Development at Geneic Sciences • Co-founder and Director of Clinical and Regulatory Affairs and Director of Cell Engineering at Genetic Therapy, Inc. • Mark J. Cooper M.D.(Sr. VP Science and Medical Affairs) • Co-founder of Copernicus Therapeutics, Inc. • Associate Professor, Oncology at CWRU • Oncology Fellowship, NCI , NIH • Joseph Ashley(Chairman of the Board) • Chief Financial/Business Development Officer(To be hired)

14. Key Achievements To Date • $19 M equity investment • $4 M support from CFF, state of Ohio, CDC, NIH • Human clinical trial data (Phase I/II) • Strong IP position • Unique, powerful mechanism of action • Preclinical data to support multiple other applications of core technology • Initiating ~$15M Series B financing round

15. Use of Series B Funds • Milestones 2006 • Complete lung aerosol CF trial • Initiate at least one additional product development • Corporate partnerships • Obtain additional non-diluting support • Augment management team • Milestones 2007 • Initiate multi-dose CF trial, complete in 2008 • Initiate and complete at least one additional product clinical trial

16. ConclusionCopernicus Therapeutics, Inc • Lead product for CF with excellent toxicology profile and demonstrated biological effect in patients • Technology solves the problems with past attempts to develop nucleic acid therapeutics • Platform technology can generate products for multiple indications • IP estate for compacting nucleic acids protects lead product and will be attractive to large pharma/biotech • CF product demonstrates proof-of-concept for technology platform with a large market application

17. “Size Does Matter” $ rmoen@cgsys.com Copernicus Competition www.cgsys.com Smaller is Better