Soligenix Announces Combination Vaccine for Ricin and Anthrax Achieves Simultaneous Protection

PRINCETON, N.J., July 9, 2014 /PRNewswire/ -- Soligenix, Inc. (OTCQB: SNGX) (Soligenix or the Company), a clinical stage biopharmaceutical company focused on developing products to treat serious inflammatory diseases where there remains an unmet medical need, as well as developing several biodefense vaccines and therapeutics, announced today that the combination of RiVax™ and VeloThrax™ induces protective immunity to both ricin toxin and anthrax toxin exposure.  RiVax™ is the Company's candidate vaccine for the prevention of exposure to ricin toxin using a unique antigen that is completely devoid of the toxic activity of ricin.  VeloThrax™ is the Company's candidate vaccine that employs a derivative of recombinant protective antigen, termed Dominant Negative Inhibitor (DNI), which is a candidate for inclusion in a next generation anthrax vaccine.

When administered as single a vaccine, each vaccine induced antibodies that were capable of neutralizing the toxin from which the vaccine had been derived.  VeloThrax™ induced neutralizing antibodies against anthrax toxin and RiVax™ induced antibodies against ricin toxin.  When combined, the dual vaccine induced antibodies that were reactive against both toxins and these neutralizing antibodies were detected until at least 200 days after the immunization regimens.  Consequently, the combined vaccination provided protection to exposure to both ricin toxin and anthrax toxin that persisted for at least six months after 2 vaccinations, suggesting that long-term immunity upon simultaneous vaccination can be achieved.

Soligenix performed these studies in collaboration with the Wadsworth Institute of the New York State Department of Health, with Dr. Nicolas J. Mantis, Dr. David Vance and collaborators under the aegis of a $9.4 million cooperative grant from the National Institute of Allergy and Infectious Diseases (NIAID). The potency of the vaccine combination was demonstrated in preclinical studies evaluating both production of antibody levels and survival after toxin challenge.

"We are pleased that we have been able to show that the combination of vaccines for these two very important biothreats can be accomplished.  The demonstration of simultaneous immunity to ricin toxin and anthrax is a step towards multivalent vaccines that can be used in the event of a national emergency," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "Both of these vaccines are being developed for military personnel and emergency first responders, and thus it would be extremely useful if the vaccines could be administered simultaneously without compromising the response to either vaccine, while still providing protection against whichever toxin might be encountered. Multivalent vaccines will achieve more efficient vaccination with fewer injections; this has the potential to be a distinct advantage in deployment of vaccines if any biothreat agent is actually used as a weapon and will be more useful for vaccination of military personnel and first responders. We intend to develop the combination vaccine using ThermoVax™, our proprietary system for stabilizing vaccines for stockpiling and for distribution of vaccines outside of normal cold chain requirements."

About Ricin Toxin

Ricin toxin is a plant toxin thought to be a bioterror threat because of its stability and high potency as well as the large worldwide reservoir created as a by-product of castor oil production. Exposure to ricin results in local tissue necrosis, and general organ failure leading to death within several days of exposure. Ricin is a ribosome inactivating protein (RIP) and a potent member of the AB family of toxins. The enzymatic A subunit (RTA) is an RNA-N-glycosidase which cleaves a specific adenine residue with eukaryotic 28S ribosomal RNA, leading to protein synthesis arrest and cell death. The potential use of ricin toxin as a biological weapon has been highlighted in an FBI terrorism report, which states that "Ricin and the bacterial agent anthrax are emerging as the most prevalent agents involved in WMD investigations" (http://www.fbi.gov/stats-services/publications/terrorism-2002-2005/terror02_05.pdf).

There are currently no effective means to prevent the effects of ricin intoxication. The successful development of an effective vaccine against ricin toxin may act as a deterrent against the actual use of ricin as a biological weapon and could be used in rapid deployment scenarios in the event of a biological attack. RiVax™ would potentially be added to the Strategic National Stockpile and dispensed in the event of a terrorist attack.

About Anthrax

Anthrax is an acute infectious disease that is easily transmitted to humans by environmentally durable spores that are produced by gram positive bacterium Bacillus anthracis. Because the spores are robust and contagious, anthrax is considered a Category A bioterror threat.  Anthrax infection can occur in three forms: cutaneous (skin), inhalation, and gastrointestinal. Inhaled spores can cause a rapidly progressing form of anthrax since the spores are transported to lymph nodes near the lungs where they germinate, releasing vegetative bacteria into the bloodstream.  After infection in the bloodstream, the bacteria secrete a complex series of toxin components that make up anthrax toxin, resulting in overwhelming toxemia that causes shock and organ failure. The toxin component that binds to the surface of cells is Protective Antigen (PA).  Antibodies targeting PA can neutralize the secreted toxins, and recombinant PA (rPA) and its derivatives are targets for development of highly purified next generation anthrax vaccines.  PA is the major antigen in the currently licensed anthrax vaccine adsorbed (AVA, Biothrax™).

Treatment of anthrax involves long-term antibiotic therapy, since ungerminated spores can lie dormant in the lungs for up to 60 days. Only a few inhaled spores can cause inhalational anthrax. Once the toxin has entered the bloodstream, antibiotics are ineffective, and only toxin-specific therapy is effective. Passively transferred antibodies can neutralize anthrax toxins and can be used post-exposure in conjunction with antibiotics. Because of the long residence time of spores in the lung, it is possible to vaccinate post-exposure, but the onset of neutralizing antibodies must occur during the period of antibiotic therapy.

About RiVax™

RiVax™ is Soligenix's proprietary recombinant subunit vaccine developed to protect against exposure to ricin toxin. With RiVax™, Soligenix is a world leader in the area of ricin toxin vaccine research.

RiVax™ contains a genetically altered version of ricin A chain containing two mutations that inactivate the inherent toxicity of the ricin molecule. A Phase 1A clinical trial was conducted with a formulation of RiVax™ that did not contain an adjuvant. This trial revealed dose dependent seroconversion as well as lack of toxicity of the molecule when administered intramuscularly to human volunteers. The adjuvant-free formulation of  RiVax™ induced toxin neutralizing antibodies that lasted up to 127 days after the third vaccination in several individuals.  To increase the longevity and magnitude of toxin neutralizing antibodies, RiVax™ was formulated with an adjuvant of aluminum salts (known colloquially as Alum) for a Phase 1B clinical trial.  Alum is an adjuvant that is used in many human vaccines, including most vaccines used in infants. The results of the Phase 1B study indicated that Alum adjuvanted RiVax™ was safe and well tolerated, and induced greater ricin neutralizing antibody levels in humans than adjuvant-free RiVax™. In preclinical animal studies, the Alum formulation of RiVax™ also induced higher titers and longer lasting antibodies than the adjuvant-free vaccine.

The development of RiVax™ has been sponsored through a series of overlapping grants from both the NIAID and US Food and Drug Administration (FDA), which were granted to Soligenix and to University of Texas Southwestern (UTSW) where the vaccine originated. To date, Soligenix and Dr. Ellen Vitetta and colleagues at UTSW have collectively received approximately $25 million in grant funding from the NIAID for development of RiVax™ and related vaccine technologies.

About VeloThrax™

VeloThrax™ is Soligenix's proprietary vaccine to prevent exposure to anthrax. VeloThrax™ consists of a hyperimmunogenic derivative, termed DNI (Dominant Negative Inhibitor), of rPA (recombinant protective antigen) that is formulated with adjuvants to induce rapid protective immunity in fewer vaccinations than the currently licensed anthrax vaccine.  The DNI vaccine antigen is an analog of rPA containing two mutations that prevent translocation of the anthrax holotoxin into cells, resulting in higher immune responses.  It has been shown that animals vaccinated with the DNI antigen induced higher levels of antibodies to toxin and maintained high levels of protective antibody titers for up to one year without booster injections of antigen. The DNI vaccine was originally developed in the laboratory of Dr. John Collier and colleagues at Harvard University and has been developed as a post exposure therapeutic for exposure to anthrax.

Soligenix has obtained an exclusive license with Harvard for the development of DNI as a pre- and post exposure vaccine for anthrax.  When combined with ThermoVax™ technology, the DNI vaccine has also shown stability at temperatures as high as 70 degrees Celsius (158 degrees Fahrenheit).  The development of VeloThrax™ using the DNI antigen has been sponsored through a NIAID cooperative grant to Soligenix and is a candidate for a next generation anthrax vaccine.

About ThermoVax™

ThermoVax™ is a technology that is designed to eliminate the standard cold chain production, distribution and storage logistics required for most vaccines. Cold chain requirements add considerable cost to the production and storage of current conventional vaccines. According to the Biopharma Cold Chain Sourcebook of 2010, 98% of all vaccines (with a total value of $20.6 billion) require shipment through cold chain. Elimination of the cold chain would also enhance the utility of these vaccines for emerging markets and for other applications requiring but lacking reliable cold chain capabilities. Further, the World Health Organization (WHO) reports that 50% of all global vaccine doses are wasted because they are not kept within required temperature ranges.  NIAID has also highlighted the priority of technologies for biodefense vaccines that focus on broad spectrum approaches including vaccine adjuvants and temperature stabilization for long shelf life, rapid onset of immunity, and surge capacity for production.  For vaccines that are intended for long-term stockpiling, such as for use in biodefense or in pandemic situations, the utilization of ThermoVax™ has the potential to facilitate easier storage and distribution of strategic national stockpile vaccines in emergency situations.

The technology utilizes precise lyophilization of protein immunogens with conventional aluminum adjuvants in combination with secondary adjuvants for rapid onset of protective immunity where protective immunity is desired with the fewest number of vaccinations.  RiVax™ and VeloThrax™ are extremely labile in their liquid form requiring careful management under refrigerated conditions at 4 degrees Celsius (39 degrees Fahrenheit).  By employing ThermoVax™ during their final formulation, it is possible to produce stable and potent vaccines that are capable of withstanding temperatures at least as high as 40 degrees Celsius (104 degrees Fahrenheit) for up to one year.

The underlying technology has been developed by Drs. John Carpenter and Theodore Randolph at the University of Colorado. The vaccine technology is being developed in collaboration with SRI International, the University of Kansas, the Wadsworth Center of the New York State Department of Health, and the Tulane National Primate Research Center under the sponsorship of the cooperative grant from NIAID.

About Soligenix, Inc.

Soligenix is a clinical stage biopharmaceutical company focused on developing products to treat serious inflammatory diseases where there remains an unmet medical need, as well as developing several biodefense vaccines and therapeutics. Soligenix is developing proprietary formulations of oral BDP (beclomethasone 17,21-dipropionate) for the prevention/treatment of gastrointestinal disorders characterized by severe inflammation, including pediatric Crohn's disease (SGX203), acute radiation enteritis (SGX201) and chronic Graft-versus-Host disease (orBec^®), as well as developing its novel innate defense regulator (IDR) technology SGX942 for the treatment of oral mucositis.

Through its BioDefense Division, Soligenix is developing countermeasures pursuant to the Biomedical Advanced Research and Development Authority (BARDA) Strategic Plan of 2011-2016 for inclusion in the US government's Strategic National Stockpile. Soligenix's biodefense products in development are a recombinant subunit vaccine called RiVax™, which is designed to protect against the lethal effects of exposure to ricin toxin and VeloThrax™, a vaccine against anthrax exposure. RiVax™ has been shown to be well tolerated and immunogenic in two Phase 1 clinical trials in healthy volunteers. Both RiVax™ and VeloThrax™ are currently the subject of a $9.4 million NIAID grant supporting development of Soligenix's new vaccine heat stabilization technology known as ThermoVax™.  Soligenix is also developing OrbeShield™ for the treatment of gastrointestinal acute radiation syndrome (GI ARS) under a BARDA contract award valued up to $26.3 million and a NIAID contract award valued up to $6.4 million. OrbeShield™ has previously demonstrated statistically significant preclinical survival results in a canine model of GI ARS funded by the NIAID.  Additionally, Soligenix has an exclusive worldwide collaboration with Intrexon Corporation (NYSE: XON) focused on the joint development of a treatment for Melioidosis, a high priority biothreat and an area of unmet medical need.

For further information regarding Soligenix, Inc., please visit the Company's website at www.soligenix.com.

This press release contains forward-looking statements that reflect Soligenix, Inc.'s current expectations about its future results, performance, prospects and opportunities, including but not limited to, potential market sizes, patient populations and clinical trial enrollment.  Statements that are not historical facts, such as "anticipates," "estimates," "believes," "intends," "potential," or similar expressions, are forward-looking statements.  These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements.  Soligenix cannot assure you that it will be able to successfully develop, achieve regulatory approval for or commercialize products based on its technologies, particularly in light of the significant uncertainty inherent in developing vaccines against bioterror threats conducting preclinical and clinical trials of vaccines, obtaining regulatory approvals and manufacturing vaccines, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that it will be able to successfully obtain any further funding to support product development and commercialization efforts, including grants and awards, maintain its existing grants which are subject to performance requirements, enter into any biodefense procurement contracts with the US Government or other countries, that it will be able to compete with larger and better financed competitors in the biotechnology industry, that changes in health care practice, third party reimbursement limitations and Federal and/or state health care reform initiatives will not negatively affect its business, or that the US Congress may not pass any legislation that would provide additional funding for the Project BioShield program.  These and other risk factors are described from time to time in filings with the Securities and Exchange Commission, including, but not limited to, Soligenix's reports on Forms 10-Q and 10-K.  Unless required by law, Soligenix assumes no obligation to update or revise any forward-looking statements as a result of new information or future events.

SOURCE Soligenix, Inc.