Hemispherx's Ampligen(R) Provides Anti-Tumor Activity Analogous to Emerging Immune Checkpoint Inhibitors

Hemispherx Biopharma, Inc.

(the "Company" or "Hemispherx"), announced today further progress on developing Ampligen® (rintatolimod) as a potential therapeutic complement to a new molecular class of anti-tumor drugs termed immune checkpoint inhibitors or PD-1 inhibitors (also called Programmed Death inhibitors). PD-1 inhibitors act to unleash the body's own immune system to scavenge/ destroy tumors: remarkable success to date clinically has been reported by Bristol Meyers Squibb (BMS), Merck, Genetech and Novartis on a variety of human tumors including malignant melanoma and metastatic renal cancer with PD inhibitors. In some of these cases, full regulatory approval of commercialization for PD-1 inhibitors has already been received internationally or is expected to be received shortly. Objective tumor regressions are typically seen in approximately 10 to 25% of patients with PD-1 checkpoint inhibitors, such compounds have been generally well-tolerated clinically with a few exceptions noted to date. Hemispherx has active ongoing antitumor programs with Ampligen® in this research area at Georgia Regents University Cancer Center (GRU) and the Cancer Center at the University of Pittsburgh (UP). The laboratory program at GRU is supported in part by sponsored research of Hemispherx whereas the UP cancer program is supported internally at the University and by various National Institutes of Health Grants. Key to further progression in this field is to improve efficacy and speed to market by determining which combination strategies yield highest priority and which techniques can be used to overcome technical challenges of clinical monitoring and predicting immune response. Investigation of immune competent models that can be effectively translated into the clinic with expert knowledge has thus become invaluable. To that end, Professor Esteban Celis (at GRU) first reported that in animal models a dsRNA analogue of Ampligen®, Poly I: Poly C, significantly increased survival in animal tumors when administered in combination with PD-1 inhibitors (see Combinatorial Immunotherapy of Poly I - Poly C and Blockage of Program Death- Ligand 1 Induce Effective CD8 T-Cell Responses in Established Tumors, Clin Cancer Research, 2014). In follow on animal experiments with Ampligen® (Report to Hemispherx dated November, 2014), Celis has demonstrated anti-tumor properties of Ampligen® similar to those of classical PD-1 inhibitors with a resultant long term survival advantage in mouse melanoma. In particular, his experiments suggest analogous actions of Ampligen® against malignant melanoma in the animal model. Mice protected by Ampligen® and/or a PD-1 inhibitor were resistant to rechallenge with viable melanoma cells in the absence of drug(s), indicating a "memory effect", which is most likely mediated by anti-melanoma cytotoxic CD8+ cells. Immune mechanisms may account for an apparent long term benefit of Ampligen® in melanoma (see below). Dr. Kalinski (UP) demonstrated that carefully coordinated administration of selected immune modulatory agents, including TLR3 agonists, type I interferons, and cyclooxygenase inhibitors, in conjunction with immunization strategies, substantially alters the character of induced immunity, the nature of cellular infiltrates, and the natural history of the induced immune response (see Hemispherx press release dated December 2, 2014) http://www.hemispherx.net/content/investor/default.asp?goto=763. More information on this research program utilizing Ampligen® as a component to help alter the immunological microenvironment around tumors to boost anti-tumor response can be found at: http://www.upmc.com/media/NewsReleases/2013/Pages/pitt-team-aims-to-change-tissue-microenvironment-to-fend-off-cancerous-tumors.aspx. Hemispherx views the potential use of Ampligen® as a component of cancer immunotherapy to be an important research area and a significant opportunity of the Company's product development. The Company's near term focus in cancer is to engage in a series of collaborations with renowned cancer research experts at premier institutions to help define the best mode of integrating Ampligen® into immunotherapy strategies for the treatment of cancer. These collective recent data provide a further rationale for therapeutic combination of Ampligen®-based CKM (chemokine modulation) with PDL1 blockers and PD-1 blockers. Additional experiments, including advanced clinical trials, will be necessary to establish whether these findings translate to enhanced survival or other clinical benefit in patients with malignant melanoma, metastatic renal cancer, or other conditions. Increased survival observed in early Phase I/II clinical trials by Hemispherx in cancer may be explained by immune enhancement. Hemispherx is actively exploring collaborative studies with potential partners in both the USA and Europe. According to a recent Bioworld report (November 24, 2014) immune-oncology drug combinations may well be on the way to becoming a multi-billion dollar market.