COMPARATIVE ANTI-ANGINAL THERAPEUTIC APPROACHES

During the past two decades several drugs have been approved by the FDA for the management of chronic stable angina pectoris, including beta-blockers, nitrates and calcium channel blockers. These drugs were approved based upon improvement in total ETT time and, in general, have demonstrated placebo-corrected increases of approximately 20 to 50 seconds. However, no new class of medications to treat angina has been approved for over 15 years. Currently, fatty acid oxidation inhibitors such as Ranolazine are being developed as a potential new alternative to or addition to existing therapies. The clinical trial experience in AGENT-3 suggests that in patients with more severe angina, Generx, after a one-time administration, can produce sustained increases in total ETT time that are clinically meaningful when considered in the context of these available therapies. Most importantly, the effects of Generx have been demonstrated in patients who are already receiving one or more chronic anti-anginal medications.

Looking comparatively, the Ranolazine clinical trial data suggest that the magnitude of its effect is similar to the currently available drugs. In the CARISA trial, Ranolazine achieved a 24 second improvement in total ETT time over placebo at trough drug levels (as defined in the trial protocol). In addition to drug therapy, mechanical revascularization procedures such as percutaneous coronary intervention ("PCI") and coronary artery bypass surgery graft ("CABG") surgery are commonly employed interventional procedures used to manage patients with chronic angina. While there have been few published controlled clinical trials of PCI or CABG surgery that have collected ETT data, two studies that have directly compared PCI and CABG surgery using ETT have shown sustained improvements in total ETT time of approximately 90 to 114 seconds for PCI and 132 to 174 seconds for CABG surgery.

Anti-Anginal Therapeutic Approaches
Comparative Clinical Data Based on
Total Exercise Treadmill Time: Change from Baseline

In the larger subset of patients over 55 years of age who were classified as CCS Class III or Class IV (n=169), statistically significant improvements were also observed in ETT parameters of patients receiving mdFGF-4 when compared to placebo. Total exercise time was significantly greater at Week 12 (10e10 vp: p=0.020) and approached significance at 6 months (10e9 vp: p=0.071, 10e10 vp: p=0.084). Statistically significant improvements versus placebo were also observed in the time to onset of angina at 12 weeks (10e9 vp: p=0.029, 10e10 vp: p=0.056) and 6 months (10e9 vp: p=0.001, 10e10 vp: p=0.037) after treatment.

These data confirmed our earlier studies and suggested that the treatment could benefit patients with more serious angina that occurs as a result of advanced coronary artery disease. This may generally target patients who have had previous interventions such as angioplasty or bypass surgery, but have recurrent angina despite drug therapy. Furthermore, based on this substantial human clinical experience with Generx, coupled with unique insights regarding a particularly "responsive" patient population for what is considered to be the key efficacy end-point, the Company believes that Generx has the potential to obtain approvable clinical data in a pivotal trial in the foreseeable future and ahead of potential competition.

Based on this analysis, we now plan to redesign Schering's Phase 2b/3 clinical study protocol and initiate AGENT-5, a new 100-patient clinical study that will continue to evaluate Generx's safety, assess the appropriateness of our modified clinical protocol design and reconfirm the FGF-4 angiogenic mechanism of action (utilizing advanced diagnostic cardiac imaging techniques). With positive data we hope to obtain from AGENT-5, we plan to further build on Schering's six-year clinical development activities and advance forward with AGENT-6, a new, redesigned, Phase 3 pivotal study that would be structured and powered to serve as the basis for a regulatory submission seeking marketing approval from the FDA.