A universal AMP-modified CpG adjuvant
for applications in a variety of indications
In addition to the development of ELI-004 as a component of ELI-002 for, we are developing ELI-004 as a universal AMP-modified CpG adjuvant for applications in a variety of indications and therapies. We have established rapid manufacturing under current good manufacturing practice, or cGMP, standards at a greater than 10-gram production scale, and we anticipate that we will have sufficient cGMP material available for use in clinical development activities. The AMP-modification is designed to concentrate and retain the smaller molecular size CpG in the lymphatic system. We are evaluating its use in combination with a variety of disease-specific antigens of smaller molecular size, that are AMP-modified to stimulate a powerful and sustained immune response as well as in combination with unmodified (native) antigens. Our preclinical results demonstrate the potential for ELI-004’s inherent capabilities and distinguish its immune-boosting strength. In addition, we are in the early stages of evaluating an expanded portfolio of next-generation adjuvants, including various AMP-modified toll-like receptor, or TLR, and damage-associated molecular pattern, or DAMP, candidates.
In previous clinical studies conducted by third parties, CpG-containing oligonucleotides have been shown to be both well tolerated and to exert immune-stimulatory effects through activation of the endosomal TLR-9 pathway present in human antigen-presenting dendritic cells and B cells. Mechanistic studies have demonstrated the ability of CpG-containing oligonucleotides to induce TLR-9 dependent innate immune activation and, subsequently, elicit adaptive immunity in humans. The specific CpG, 7909, which we incorporate into our vaccine configurations, has been shown to induce both B cell proliferation, and dendritic cell maturation in clinical trials. Further, CpG-7909 elicited target-specific adaptive immunity when given in combination with an antigen. Safety assessments in these and other trials have defined the absorption, distribution, metabolism and elimination profiles of oligonucleotides including those containing phosphorothioate linkages, such as CpG-7909. Adverse events were consistent with TLR-9 activation and included local injection site reactions and flu-like symptoms. Few serious adverse events have been observed. Our thoughtfully designed AMP modified CpG adjuvant may have the potential to induce an enhanced immune response due to its specific engagement with the lymph nodes.