| | | | | | | Lead Program | | | | | | | | NovaDigm’s lead vaccine candidate, NDV-3, is a prophylactic vaccine containing a candidal surface glycoprotein antigen. This candidate was developed as a result of research in our scientific founders’ labs demonstrating that several members of the agglutinin-like sequence (Als) family of proteins induce protective immunity in preclinical models, which confers a high survival rate following a challenge with highly virulent doses of one of several species of Candida or against one of several strains of Staphylococcus aureus (S. aureus), including methicillin-resistant S. aureus (MRSA). NovaDigm selected one of these proteins, Als3, as the most effective of these proteins to move forward as the antigen in NDV-3, which is scheduled to begin human clinical trials in 2010. | | | | | | NDV-3 is a formulation of the recombinant N-terminus of the Candida surface protein Als3 and the adjuvant Alhydrogel®. Alhydrogel® (often referred to as “alum”) has a long track record of being a safe and effective adjuvant in a number of commercially available vaccines. | | | | | | In preclinical studies, NDV-3 stimulates both strong Type I (T-cell-mediated) and Type II (B-cell-mediated) immune responses. The vaccine has demonstrated efficacy in reducing the mortality of otherwise highly lethal infections due to both Candida and S. aureus. Interestingly, we have demonstrated that while the vaccine evokes very high antibody levels, the mechanism of action in a preclinical model is primarily Type I (T-cell-mediated). This promising finding suggests that the vaccine may enhance immunity against these organisms even after infection has been established.1,2 | | | | | | NDV-3 is the first vaccine to demonstrate protective efficacy against both fungal and bacterial pathogens. We believe this observation results from a close structural and functional relatedness in the mechanisms by which Candida and S. aureus adhere to, colonize, and penetrate tissues in mammals.3 Given the overlapping risk factors for both S. aureus and Candida infections, the increasing worldwide prevalence of these risk factors, and the increasing difficulty in treating these infections, we intend to advance development of this vaccine for clinical indications for both pathogens. | | | | | | NovaDigm is currently completing the preclinical development activities required to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for NDV-3. | | | References
1. Spellberg BJ, Ibrahim AS, Yeaman MR, Lin L, Fu Y, Avanesian V, Bayer AS, Filler SG, Lipke P, Otoo H, and Edwards JE Jr., The antifungal vaccine derived from the recombinant N terminus of Als3 protects mice against the bacterium Staphylococcus aureus. Infect.Immun. 2008; 76:4574-580.
2. Spellberg BJ, Ibrahim AS, Lin L, Avanesian V, Fu Y, Lipke P, Otoo H, Ho, T and Edwards JE Jr., Antibody titer threshold predicts anti-candidal vaccine efficacy even though the mechanism of protection is induction of cell-mediated immunity. J. Inf. Dis. 2008; 197:967-71.
3. Sheppard DC, Yeaman MR, Welch HW, Phan QT, Fu Y, Ibrahim AS, Filler SG, Zhang M, Waring AJ and Edwards JE, Jr., Functional and structural diversity in the Als protein family of Candida alibicans. J. Biol. Chem. 2004; 279:30480-9. | | | | | | | | | |
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