Ampligen®

Nucleic acid compounds represent a potential new class of pharmaceutical products that are designed to act at the molecular level for treatment of human diseases. The Hemispherx Biopharma drug technology utilizes specifically-configured RNA. The Hemispherx double-stranded RNA drug product, trademarked Ampligen®, an experimental, unapproved drug, which is administered intravenously, is in human clinical development for various therapeutically oriented studies, including treatment for CFS/ME, HIV, renal cell carcinoma and malignant melanoma.

Based on the results of pre-clinical studies and clinical trials, Hemispherx believes that Ampligen®, an experimental agent, may have broad-spectrum anti-viral and anti-cancer properties. Approximately 500 patients have received Ampligen® in clinical trials authorized by the Food and Drug Administration (“FDA”) at over twenty clinical trial sites across the U.S., representing the administration of more than 40,000 doses of this drug, and Ampligen® is available only through clinical trials for limited indications.

Clinical trials already conducted by Hemispherx U.S. include treatments of CFS/ME, other infectious diseases such as Hepatitis B, HIV, and clinical trials for cancer including patients with renal cell carcinoma and malignant melanoma.  Certain of these studies to date have not been well-controlled and accordingly additional tests will be necessary for support of regulatory approvals.

Hemispherx U.S. has been issued certain patents on the use of Ampligen® alone and Ampligen® in combination with certain other drugs including AZT, ddI, ddC, interferon and/or IL-2, for the treatment of HIV.

A second experimental drug that Hemispherx U.S. has patented is Poly A:Poly U for Hepatitis B, which has been studied in advanced clinical trials primarily conducted by a major European pharmaceutical company. Hemispherx U.S. also has licensed a series of patents on Oragen™, experimental drugs believed by the company to be a broad-spectrum oral anti-viral drugs of the second-generation RNA drugs developed at Temple University. Hemispherx's experimental compounds, no members of which have yet been determined "safe and effective" by regulatory authorities, are accordingly only available legally in certain authorized trials and tests; in vitro (outside the body) tests are also not necessarily indicative of any evidence of clinical benefits or advantages.  But the focus of Hemispherx is on Ampligen® as a treatment for CFS/ME and HIV.

The Company believes that Ampligen® has been generally well tolerated with a low incidence of clinical toxicity, particularly given the severely debilitating or life threatening diseases that have been treated.  A mild flushing reaction has been observed in approximately 15% of patients treated in our various studies.  This reaction is occasionally accompanied by erythema, a tightness of the chest, tachycardia, anxiety, shortness of breath, subjective reports of "feeling hot," sweating and nausea.  The reaction is usually infusion-rate related and can generally be controlled by slowing the infusion rate.  Other adverse side effects include liver enzyme level elevations, diarrhea, itching, urticaria (swelling of the skin), bronchospasm, hypotension, photophobia, rash, bradycardia, transient visual disturbances, arrhythmias, decreased platelets and white blood cell counts, anemia, dizziness, confusion, elevation of kidney function tests, occasional temporary hair loss and various flu-like symptoms, including fever, chills fatigue, muscular aches, joint pains, headaches, nausea and vomiting.  These flu-like side effects typically subside within several months. 

Alferon Low Dose Oral (LDO)®

Alferon LDO®, Hemispherx's oral form of our highly purified, natural source alpha interferon is a new dosage form of our FDA approved drug, Alferon N®, the only natural interferon currently FDA approved and available in the marketplace.  Hemispherx has initiated clinical trials as part of an accelerated evaluation of the experimental bio-therapeutic Alferon LDO (Low Dose Oral Interferon Alfa-n3 (Human Leukocyte Derived)) as a potential new experimental therapy for Avian Flu and other lethal viral diseases, which have high acute death rates. Clinical trials in human volunteers (being conducted in both the U.S. at Drexel University, Philadelphia, and shortly to commence in Hong Kong at the Princess Margaret Hospital) are designed to determine whether Alferon N, delivered in a new, experimental oral drug delivery format, can resuscitate the broad-spectrum antiviral and immunostimulatory genes. These human genes are shut down by acute lethal viral infections such as avian flu and smallpox.

Positive results in the ongoing clinical studies would potentially make Alferon LDO the first orally active interferon drug candidate and would open an opportunity leading to a wide range of potential new indications.
 

Other Products

Oragen™

Hemispherx is in the early pre-clinical stages of developing Oragen™ drugs, a nucleic acid technology related to Ampligen®. Oragen™ drugs are low molecular weight RNA compounds which Hemispherx believes, by virtue of their small size, have the potential for becoming oral, broad-spectrum treatments for various viral diseases such as HIV infection and chronic HBV infection. Hemispherx's experimental compounds, no members of which yet have been determined "safe and effective" by regulatory authorities and are accordingly only available legally in certain authorized trials and tests; in vitro (outside the body) tests are also not necessarily indicative of any evidence of clinical benefits or advantages.   The technology for these products has been developed in part by Hemispherx U.S. and developed in part by Temple University, which has licensed to Hemispherx U.S. certain technology for commercial use on an exclusive basis, subject to certain limited exceptions.

Initial laboratory studies show that these drugs can resist destruction, an important factor in order for compounds to enter the blood stream in an intact form. Results from in vitro studies conducted in collaboration with the National Institute of Allergy and Infectious Diseases indicate that Oragen™ products may inhibit HBV infection, and in vitro studies conducted in collaboration with the National Cancer Institute and Johannes Gutenberg University in Mainz, Germany, indicate that Oragen™ products may inhibit HIV infections. Hemispherx's experimental compounds, no members of which yet have been determined "safe and effective" by regulatory authorities and are accordingly only available legally in certain authorized trials and tests; in vitro (outside the body) tests are also not necessarily indicative of any evidence of clinical benefits or advantages.  One compound, Oragen™ 0004, has shown inhibition of HBV multiplication in vitro and another, Oragen™ 0044, has demonstrated activity against HIV in in vitro studies performed by Temple University. These two Oragen™ compounds have been produced in quantities, which Hemispherx believes, are sufficient to perform initial animal toxicology testing. Experiments with mice at the University of Toronto indicate that Oragen™ 0004 may inhibit mouse hepatitis virus, and that Oragen™ 0004 may be absorbed after oral delivery. There has been no human clinical testing of Oragen™ products to date. There can be no assurance that human clinical testing, if initiated, will yield results consistent with those achieved in in vitro or animal testing. Hemispherx's experimental compounds, no members of which yet have been determined "safe and effective" by regulatory authorities and are accordingly only available legally in certain authorized trials and tests; in vitro (outside the body) tests are also not necessarily indicative of any evidence of clinical benefits or advantages.  Clinical trials may be carried out beginning in 2002 and 2003.

Hemispherx believes that Oragen™ drugs may exert activity through two intracellular mechanisms. First, they may activate the intracellular "latent" RNase L to degrade viral RNA. Second, they may inhibit the HIV replication enzyme, reverse transcriptase, by binding to a different site on the enzyme from that bound by conventional anti-HIV compounds such as AZT. Hemispherx' belief in the potential effects of these compounds is based, in part, on the collaborative in vitro studies with the National Cancer Institute referred to above. Certain in vitro experiments performed at Vanderbilt University indicate that certain human immune cells may be protected from cell death caused by HIV infection by treatment with Oragen™ drugs. Under sponsorship of the National Institute for Allergy and Infectious Diseases, in vitro studies at Georgetown University also demonstrated that Oragen™ drugs may inhibit the replication of human HBV virus. In each of the in vitro studies, no substantial cell toxicity was observed at concentrations, which inhibit the applicable virus.  Hemispherx's experimental compounds, no members of which yet have been determined "safe and effective" by regulatory authorities and are accordingly only available legally in certain authorized trials and tests; in vitro (outside the body) tests are also not necessarily indicative of any evidence of clinical benefits or advantages.

Hemispherx believes Oragen™ drugs may work at a different stage of the anti-viral and anti-cancer response chain than Ampligen® and therefore may be useful where the activity of Ampligen® is limited.

Polyadenur™

Polyadenur™ is the trademark of Poly A : Poly U RNA developed and tested independently of Hemispherx U.S. by laboratories Beaufour Ispon, a French corporation. Beaufour Ispon conducted Phase II/III trials in Hepatitis B in conjunction with interferon. The results as compared with the use of interferon alone were encouraging based on a reduction in virus and improvement in liver parameters. Poly A : Poly U application to Hepatitis B is covered by Hemispherx U.S. patents and this has been confirmed recently by the European patent application review board. The strategy to follow is still to be finalized as Ampligen® also had been studied in Hepatitis B.