Company Overview of Vaccinex, Inc.

Vaccinex Inc. announced the dosing of the first patient in a Phase Ib/II study of VX15/2503, an investigational humanized anti-semaphorin 4D IgG4 monoclonal antibody, in combination with avelumab, a human anti-PD-L1 IgG1 monoclonal antibody, in patients with advanced non-small cell lung cancer (NSCLC). The trial is being conducted under a clinical collaboration agreement announced last year between Vaccinex and Merck KGaA, Darmstadt, Germany. The clinical trial, short-named ‘CLASSICAL – Lung’, is a multi-center, open-label study designed to evaluate the safety and potential efficacy of the combination of VX15/2503 and avelumab in patients with advanced NSCLC who have not previously received immunotherapy. The design of the trial consists of a dose escalation phase to determine the recommended Phase II dose of VX15/2503 in combination with avelumab, followed by an expansion phase to enroll up to a total of 40 patients with NSCLC. In preclinical studies conducted by Vaccinex, anti-semaphorin 4D antibodies have been shown to increase infiltration of tumoricidal immune cells while simultaneously reducing multiple types of immunosuppressive cells in tumors. In these studies, anti-semaphorin 4D antibody was found to synergize with a checkpoint inhibitor antibody to promote tumor eradication. The CLASSICAL – Lung study marks the first clinical trial to evaluate VX15/2503 in combination with a checkpoint inhibitor.

Vaccinex, Inc. announced that a pre-planned analysis of data from Cohort A of the SIGNAL trial was completed. In June 2015, Vaccinex, the Huntington Study Group (HSG), and the University of Rochester's Clinical Trials Coordination Center launched SIGNAL, the first clinical trial to investigate a monoclonal antibody as a potential treatment for Huntington's disease (HD). The SIGNAL trial is a Phase 2, multi-center, randomized, double-blinded, placebo controlled study in subjects with late prodromal and early manifest HD to assess the safety, tolerability, pharmacokinetics, and efficacy of VX15/2503 (VX15), an antibody to semaphorin 4D, a molecule that has been shown to regulate the activation and migration of inflammatory cells and to inhibit differentiation of oligodendrocyte precursors in the brain. The study consists of two Cohorts, A and B. Thirty-six participants were randomized into the now completed Cohort A to receive monthly infusions of either VX15 or placebo for six months, in a double-blind fashion. All participants in Cohort A subsequently received open-label VX15 for another five months, followed by a three-month safety follow-up. A significant relationship between decreasing imaging measures and disease progression in HD was previously demonstrated in the much larger PREDICT-HD and TRACK-HD studies (1-3). A major focus of the present SIGNAL study, therefore, includes the use of brain imaging measures, Magnetic Resonance Imaging (MRI) and fluorodeoxyglucose (FDG)-positron emission tomography (PET, FDG-PET), in order to investigate the impact of treatment on changes in brain structure (MRI) and metabolic activity (FDG-PET).  Cohort A participants in the SIGNAL study underwent imaging at baseline and after 6 and 11 months of treatment. A second goal of the study was to collect data on the variance of potential treatment effects of VX15 on quantitative motor and cognitive assessments so as to project the required group size for investigation of such effects in Cohort B. Analysis of imaging data from subjects in Cohort A suggests that treatment with the VX15 antibody moderates or prevents the decrease in MRI volume and metabolic activity in many brain cortical regions which otherwise decreased at an annualized rate of 2% to 3% in the placebo control group. Similar imaging changes were detected in both early manifest and late prodromal subjects, particularly as regards changes in metabolic activity. Although only 36 subjects were enrolled in Cohort A and the duration of treatment was relatively short, the data encourage further investigation of clinical effects of treatment. Accordingly, the results of motor and cognitive assessments provided important guidance for projecting the group size required to detect clinical effects in the continuing Cohort B study. The SIGNAL trial is based on prior research on neurodegenerative disease mechanisms, where it was demonstrated in preclinical models that semaphorin 4D triggers activation of both microglia and astrocytes, the main innate inflammatory cells of the central nervous system(4,5). Chronic activation of microglia and astrocytes has been implicated as a potentially important disease mechanism in HD, progressive multiple sclerosis (MS) and other neurodegenerative disorders. VX15 antibody is designed to block the functional activity of SEMA4D.

Vaccinex, Inc. Presents at LifeSci Advisors' Corporate Access Event, Jan-09-2017 . Venue: Sir Francis Drake Hotel, San Francisco, California, United States.