Hemispherx’s Ampligen Provides Anti-Tumor Activity Analogous to Emerging Immune Checkpoint Inhibitors

Philadelphia, PA, December 16, 2014: Hemispherx Biopharma, Inc. (NYSE MKT: HEB) (the “Company” or “Hemispherx”), recently announced 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.

​About Alferon® N

Alferon® N is the only natural source, multi-species alpha interferon currently approved for sale in the U.S. Alferon® N is approved in the U.S. only for the treatment of refractory or recurring external genital warts caused by human papilloma virus in patients 18 years of age, or older. Positive results against Ebola in vitro have been reported to the Company by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Clinical trial data will be necessary to establish human efficacy of Alferon® N for Ebola virus and/or its potential addition benefit to any CKM regimen.

​About Ampligen®

Ampligen®, an experimental therapeutic, is a new class of specifically-configured ribonucleic acid (RNA) compounds targeted as potential treatment of diseases with immunologic defects and/or viral causation.

​About Hemispherx Biopharma

Hemispherx Biopharma, Inc. is an advanced specialty pharmaceutical company engaged in the manufacture and clinical development of new drug entities for treatment of seriously debilitating disorders especially life-threatening viruses. Hemispherx’s flagship products include Alferon® N Injection® and the experimental therapeutics Ampligen® and Alferon® LDO. Ampligen® is an experimental RNA nucleic acid being developed for globally important debilitating diseases and disorders of the immune system, including Chronic Fatigue Syndrome. Hemispherx’s platform technology includes components for potential treatment of various severely debilitating and life threatening diseases including cancers. Because both Ampligen® and Alferon® LDO are experimental in nature, they are not designated safe and effective by a regulatory authority for general use and are legally available only through clinical trials. Hemispherx has patents comprising its core intellectual property estate and a fully commercialized product (Alferon® N Injection®), approved for sale in the U.S. and Argentina. The FDA approval of Alferon® N Injection® is limited to the treatment of refractory or recurrent external genital warts in patients 18 years of age or older. The Company’s Alferon N Injection® approval in Argentina includes the use of Alferon N Injection® (under the brand name “Naturaferon”) for use in any patients who fail, or become intolerant to recombinant interferon, including patients with chronic active hepatitis C infection. The Company wholly owns and exclusively operates a GMP certified manufacturing facility in the United States for commercial products. For more information please visit www.hemispherx.net.

​Disclosure Notice

The information in this press release includes certain “forward-looking” statements including without limitation statements about additional steps which the FDA may require and Hemispherx may take in continuing to seek commercial approval of the Ampligen® NDA for the treatment of Chronic Fatigue Syndrome in the United States. The production of new Alferon® API inventory will not commence until validation phases are complete. While the facility is approved by FDA under the Biological License Application (“BLA”) for Alferon®, this status will need to be reaffirmed upon the completion of the facility’s enhancements prior to commercial sale of newly produced inventory product. If and when we obtain a reaffirmation of FDA BLA status and have begun production of new Alferon® API, we will need FDA approval as to the quality and stability of the final product to allow commercial sales to resume. The final results of these and other ongoing activities could vary materially from Hemispherx’s expectations and could adversely affect the chances for approval of the Ampligen® NDA in the United States and other countries. Any failure to satisfy the FDA regulatory requirements or the requirements of other countries could significantly delay, or preclude outright, approval of Ampligen® in the United States and other countries.

Information contained in this news release, other than historical information, should be considered forward-looking and is subject to various risk factors and uncertainties. For instance, the strategies and operations of Hemispherx involve risk of competition, changing market conditions, changes in laws and regulations affecting these industries and numerous other factors discussed in this release and in the Company’s filings with the Securities and Exchange Commission. The final results of these efforts could vary materially from Hemispherx’s expectations. No evidence has suggested that Alferon® N, Alferon® LDO, and/or Ampligen® will ever be commercially approved for the new potential treatment indications mentioned in this release, including, but not limited, to a combinational regimen with antitumor drugs and/or antitumor treatments.

​Forward-Looking Statements

To the extent that statements in this press release are not strictly historical, all such statements are forward-looking, and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “intends,” “plans,” and similar expressions are intended to identify forward-looking statements. The inclusion of forward-looking statements should not be regarded as a representation by Hemispherx that any of its plans will be achieved. These forward-looking statements are neither promises nor guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond Hemispherx’s control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. Examples of such risks and uncertainties include those set forth in the Disclosure Notice, above, as well as the risks described in Hemispherx’s filings with the Securities and Exchange Commission, including the most recent reports on Forms 10-K, 10-Q and 8-K. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Hemispherx undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise revise or update this release to reflect events or circumstances after the date hereof. No evidence is suggested that Alferon® N, Alferon® LDO, and/or Ampligen® will ever be commercially approved for the new potential treatment indications mentioned in this release.