Paul Goldfarb, M.D .

1. Grand Rounds 2005 Paul Goldfarb, M.D.

2. Inovio’s Proprietary Medpulser® System Generator: • Capable of several thousand treatments •Generatessquare wave DC current Applicator: • One per patient/treatment • Usage restricted by smart-chip • Sizeable gross margin

3. Family of Applicators Adjustable length applicators utilize their needle shield to adjust needle length by twist clicking into stops set from 0 to 3cm in 0.5cm increments. Adjustable angle applicators allow the angle of the needle probe to applicator handle to be infinitely adjusted from 0º to 90º, permitting the physician to treat tumors on the lateral aspect of organs.

4. Therapeutic Platform Based on Electroporation Electroporation DC Cell Membrane After Pulse (Cell returns to original state) Cell Membrane During Pulse Cell Membrane Before Pulse Electroporation applies brief electrical pulses, inducing pores to open in the cell membrane and dramatically increasing uptake of useful drugs, genes & DNA vaccines A simple and effective system of delivering drugs or genes into cells

5. Cancer Therapy Procedure Utilizing EPT Injection of Bleomycin Electroporation Therapy (EPT) DC Electroporation Pulsing the Tumor withapplicator Cell Poration, drug enters cells Drug Surrounds Tumor Cells Cells Reseal And Die Very effective treatment requiring low level of technical skills

6. EPT Pre-clinical & Clinical Experience Tumor Type in vitro in vivo human ovarian endometrial prostate hepaticellular carcinoma Lewis lung carcinoma non-small cell lung fibrosarcoma glioma basal cell carcinoma melanoma Kaposi’s sarcoma adenocarcinoma squamous cell carcinoma oral, head and neck pancreatic liver EPT is efficacious across tumor types

7. Electroporation Therapy in Head and Neck Cancer Patient 002: lateral tongue cancer The tumor is injected with Bleomycin.

8. Electroporation Therapy in Head and Neck Cancer Patient 002: EPT Electroporation Therapy (EPT) is applied with the applicator.

9. Electroporation Therapy in Head and Neck Cancer Patient 002: 4 weeks post EPT The tumor has a definitive margin after 4 weeks.

10. Head & Neck Cancer Clinical Data Phase II, Recurrent Late Stage H&N Tumors: N.A. and Europe Bleo Only Bleo & EPT Tumors Patients CR% PR% 37 25 0 3 Tumors Patients CR% PR% OR% 20 17 30 25 55 31 25 19 39 58 18 12 28 28 56 N. America IN. America II Europe 69 54 26% 32% 57% Total Market Seeding, Newly Diagnosed H&N Tumors: Europe CR = Complete Response : Tumor shrinkage of 100% PR = Partial Response : Tumor shrinkage of 50% or greater OR = Objective Response : Clinical Response + Partial Response NED = No Evidence of Disease at treatment site on histological examination 4 weeks post treatment ED = Evidence of Disease Tumors Patients NED ED 20 20 16 4 Europe Patients had a complete response rate of 80% Excellent response rate in newly diagnosed H&N cancer patients

11. EPT Compared to Surgery • Equivalent disease control • Better tissue preservation • Better function preservation • Less cost

12. Inovio Biomedical Corporation Our Perception: A NOVEL ABLATION SYSTEM THAT USES A WELL CHARACTERIZED DRUG IN A PREVIOUSLY APPROVED ROUTE OF ADMINISTRATION TO ABLATE MALIGNANT TISSUE AND SPARE NON-MALIGNANT TISSUES IN CONJUNCTION WITH A DEVICE THAT ADMINISTERS BRIEF LOCALIZED ELECTRIC PULSES. Our Regulatory Pathway as defined by our RFD: A COMBINATION PRODUCT WITH PRIMARY REVIEW BY CDER AND CONSULTATIVE REVIEW BY CDRH WITH A RECOMMENDATION TO CONSIDER 510-K SUBMISSION FOR THE DEVICE AT TIME OF REVIEW.

13. Inovio Biomedical Corporation Original Phase III study design: A standard survival based study in patients with end stage disease where all received systemic therapy and the study group received EPT. The primary endpoint was survival Issues: • A local therapy has no benefit if the total tumor burden is not addressed by the intervention. • There is no clinical benefit [survival] to local therapy use in patients with end stage disease and this therapy would not be offered to patients in this clinical setting

14. Inovio Biomedical Corporation Current Phase III study design: • A study comparing the efficacy of EPT to surgery in patients with localized recurrent disease or second primary disease • The endpoint is enhanced preservation of function and appearance. Survival and local control will be no worse with EPT

15. Inovio Biomedical Corporation Bleomycin issues: • A well characterized generic drug • A Class 1 generic drug for parenteral administration • The device acts with a class of drugs and not a “specific drug” • Genetronics is not the MA holder for Bleomycin & will not bring the drug into commerce • No interest on the part of current license holders to relabel the drug

16. Inovio Biomedical Corporation Resolution developed with the FDA: • The label, included with each disposable applicator, will incorporate all relevant information regarding the use of the drug Bleomycin when used as part of an EPT procedure • Genetronics will monitor the available formulations of bleomycin on a routine basis to ensure continued constancy of formulation. This is already assured by the drug classification • The final approval will be through a PMA granted by CDRH with a collaborative review by CDER.

17. Inovio Biomedical Corporation Implications: •New indications may not require relabeling of the drug and will be reflected in changes to the device label. • Once initial safety issues related to Bleomycin have been reviewed by CDER, future efficacy assessments of this ablation technology might be reviewed by CDRH and approved as supplements to a PMA. • THIS MODEL PROVIDES A INOVATIVE, FLEXIBLE, PATHWAY TO REVIEW AND APPROVE DRUG- DEVICE COMBINATION PRODUCTS THAT USE CERTAIN GENERIC DRUGS.