Hemisphrex Announces Publication of Ampligen Safety Profile Across Diverse Animal Species

Hemispherx Biopharma, Inc. HEB (the "Company" or "Hemispherx") announced today the peer-reviewed publication titled "Discordant Biological and Toxicological Species Responses to TLR-3 Activation" in the current issue of the American Journal of Pathology Vol. 184 (pages 1062-1072), 2014. Toll-like receptors (TLR) are multiple proteins of the innate immune system that trigger upon activation cascades (release) of disease fighting molecules, which include enhancement of the body's immunity and interruption of the replication cycles of many different viruses. Ampligen®, an experimental therapeutic, initiates its pharmacological effects by binding TLR-3 selectively. The selectivity/ specificity of Ampligen® was first fully described by the late Nobel Laureate in Medicine, Professor Ralph Steinman of the Rockefeller University. The biological significance of the extraordinary specificity of Professor Steinman's findings is illustrated in the current manuscript. For example, all other TLR stimulators thus far studied clinically (e.g., CpG, Flagellins, etc.) trigger more pro-inflammatory cascades, which may lead to a significant side effect profile in patients. In contrast, Ampligen®, an experimental therapeutic, displayed a discordance between the rodent and human inflammatory responses. Systemic inflammatory cytokines, observed in rats, were correlated with significant acute and chronic in vivo toxicities at Ampligen® doses that elicited no detectable systemic inflammatory cytokines and minimal toxicities in primates. The lack of systemic cytokine detection is consistent with the observed minimal toxicity in primates, in contrast to the significant toxicities observed in non-primates. Rat toxicity correlates with systemic cytokine levels, and the lack of primate toxicity similarly is correlated with the lack of significant systemic inflammatory cytokine levels. Inflammatory cytokines observed in the systemic circulation in rats are associated with toxicity and are analogous to the toxicity seen in humans with lethal viral infections, such as highly pathogenic avian influenza and severe acute respiratory syndrome-CoV associated with inflammatory cytokine storms. Cytokine responses from baseline in seventy-six (76) patients with CFS enrolled in two clinical trials of Ampligen® were also examined at 32 weeks post-treatment with only one patient exhibiting a relatively high systemic TNF-α (Tumor Necrosis Factor Alpha) level. TNF-α is a cytokine with high inflammatory activity. In summary, primates including humans display a relatively down-regulated inflammatory cytokine induction pathway with TLR-3 receptor stimulation secondary to Ampligen® administration. This down regulatory effect may contribute to the favorable safety profile observed clinically with Ampligen®, an experimental therapeutic.