Hemispherx Biopharma (HEB) Ampligen Produces 100% Survival Rate in Ebola Virus Rodent Study

Hemispherx Biopharma, Inc. (NYSE: HEB) announced today the results of a new efficacy study of Ampligen® in a mouse model of Ebola virus (EBOV) infection performed by scientists at the U.S. Army Medical Research Institute of Infectious Disease (USAMRIID).

Ampligen® (rintatolimod), an experimental therapeutic, was utilized with a mouse adapted Ebola virus using multiple groups of mice with varying dosage schedules of Ampligen® given every other day. The most effective dose, resulting in 100% percent survival, corresponded to a human dose of approximately 400 mg, which has been used clinically approximately 50,000 times and has been generally well-tolerated when administered twice weekly. When higher doses of Ampligen® were used in the Ebola-infected mice, the survival rate dropped to 90%. The Ebola-infected mice treated with placebo had a 100% death rate by Day 7 post-infection.

Ebola virus disease appears to be a double-stranded RNA (dsRNA) deficiency disease in which the lethal sequelae stem from the inability of the host (mouse or human) to mount an effective innate immune response. As such, Ampligen®, an experimental therapeutic (and synthetic dsRNA), appears to directly address the underlying molecular deficiency in bio available dsRNA.

Ampligen® has a second property, potentially relevant to durable benefit in Ebola disease, in that it is believed to be insensitive to changes in viral structure and changes in molecular sequences. In a new publication in the journal mBio (Kugelman, et al. mBio 2015;6(1):e02227-14), scientists at the U.S. Army Medical Research Institute of Infectious Disease (USAMRIID), Harvard University, and Massachusetts Institute of Technology (MIT) studied genetic changes in the Ebola virus (EBOV) circulating in West Africa and concluded that genomic drift of the EBOV over time may be sufficient to block the action of otherwise potential therapies that target EBOV genetic sequences. The types of potential drugs at risk include monoclonal antibodies and small-interfering RNA (siRNA) which are scheduled to be evaluated during the current outbreak.

The two platform drugs of Hemispherx, Alferon® N and Ampligen®, both experimental therapeutics in a setting of Ebola disease, have recently both demonstrated anti-EBOV activity in culture (see Hemispherx' Press release dated November 3, 2014http://www.hemispherx.net/content/investor/default.asp?goto=805) and have mechanisms of action which are multifaceted by working through cellular "molecular cascades" rather than by targeting viral protein or genetic sequences vulnerable to mutational change (Kugelman, et al. mBio 2015;6(1):e02227-14). Cellular antiviral pathways of innate immunity are not subject to the mutational pressures of rapidly dividing viruses, which suggests that - even in the face of viral mutation – biological modifier products activating innate immunity are likely to continue to show sustained biological activity.

Although none of the experimental drugs have been approved by the U.S. Food and Drug Administration (FDA), certain of the experimental therapeutics discussed in the USAMRIID/Harvard/MIT report, are being used to treat small numbers of patients under a World Health Organization (WHO) emergency protocol. The potential impact of genomic drift on development of therapeutics for EBOV disease has already been realized for other pathogenic human virus, such as HIV and influenza. The large genetic and antigenic diversity seen in HIV has been a "major stumbling block" for development of preventative vaccines (Ndung'u and Weiss. AIDS 2012;26(10):1255-60).

In a highly mutational rate setting, use of antiviral drugs that target genomic or protein sequences, may accelerate the onset of drug resistant viral strains, as has been reported previously with influenza and application of Tamiflu (Chao, et al. J R Soc Interface 2012;9(69):648-56), thus the proposed use of experimental drugs whose action is sequence specific is not without additional theoretical risks.

Additional potentially favorable properties of Ampligen® are its well-studied and documented adverse event profile, which provides over 600 patient years of patient safety data and a proven record at manufacturing at a scale to treat more than 1,000 human subjects with this experimental therapeutic.

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