Study Results Demonstrate VeloThrax™ Vaccine with Potent Adjuvant Stimulates Rapid Onset of Immunity

PRINCETON, NJ, USA I August 7, 2014 I 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 results demonstrating the improved immunogenicity and rapid action of its anthrax vaccine, VeloThrax™.  Previous studies had demonstrated that VeloThrax™ also possesses enhanced thermostability, enabling distribution without cold chain requirements. 

VeloThrax™ is the Company’s proprietary DNI (dominant negative inhibitor) anthrax rPA (recombinant protective antigen) subunit protein vaccine.  Recent developments in the VeloThrax™ formulation have resulted in immune responses indicative of protection after no more than two administrations of the vaccine in a shortened (less than one month) vaccination regimen, in an animal model.  These results are indicative of a vaccine that can be given to humans in an abbreviated regimen, compared to the current vaccinination that requires up to five administrations over a period of 18 months for full protective immunity in humans.  Next generation anthrax vaccines have been targeting a shortened vaccination schedule with fewer vaccinations for both pre and post-exposure use.   

A rapidly acting form of VeloThrax™ has been developed by combining Soligenix’s proprietary vaccine thermostabilization platform technology, ThermoVax™, and a potent adjuvant compound to yield a vaccine that is stable to high temperatures and induces neutralizing antibodies in an animal model.  The enhanced DNI vaccine was formulated with a synthetic immunostimulatory adjuvant that activates toll-like receptor 4 (TLR-4), a receptor that is important in recognition of pathogens.  The immune responses indicative of protective immunity were observed in fewer doses than the vaccine that did not contain the additional immunostimulatory adjuvant.  In mice, stimulation of TLR-4 by the use of the synthetic adjuvant improved the outcome of vaccination by enhancing anthrax toxin neutralizing antibodies after a single immunization.  Antibodies that neutralize anthrax toxin are critical for protective immunity.

The enhanced vaccine was also stable at 40 degrees Celsius (104 degrees Fahrenheit) for at least 3 months, indicating that the synthetic adjuvant component and the DNI antigen component were both stabilized.  Furthermore, even when VeloThrax™ was stored at 40 degrees Celsius for up to 3 months prior to administration, there was no evident loss of the ability to induce antibodies that neutralize anthrax toxin. 

These studies were a continuation of studies that demonstrated that the DNI protein could be subjected to temperatures as high as 70 degrees Celsius (158 degrees Fahrenheit) for at least one month, with no evidence of denaturation in the formulated vaccine. Extensive testing of protein structure demonstrates that the thermally stressed DNI protein retained its completely native conformation after exposure to 70 degrees Celsius.

“We are very pleased that our enhanced anthrax vaccine, VeloThrax™, has demonstrated promising results indicative of rapid onset of protective immunity,” stated Christopher J. Schaber, PhD, President & CEO of Soligenix.  “These data demonstrate the potential of creating a rapidly acting anthrax vaccine with the ability to withstand temperature extremes thereby avoiding the need for cold chain management.  We believe that stability at such elevated temperatures provides a distinct advantage over other anthrax vaccine technologies currently in development.  Further, DNI rPA is highly immunogenic and offers the potential for complete immunization with just one or two doses. We expect to continue to advance VeloThrax™ development with the support of government grants and contracts.  As with all our biodefense programs, our goal is to position VeloThrax™ as a next generation anthrax vaccine for stockpiling by the US government.”

About Anthrax

Anthrax is an acute infectious disease that is easily transmitted to humans by environmentally durable spores that are produced by Bacillus anthracis.  Because the spores are robust and contagious, anthrax is considered a Category A bioterror threat by the Centers for Disease Control and Prevention (CDC). 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.  Bacteria synthesize a complex series of toxin components that make up anthrax toxin, resulting in overwhelming toxemia that causes shock and organ failure.  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 VeloThrax

VeloThrax™ is Soligenix’s proprietary vaccine to prevent disease associated with exposure to anthrax.  VeloThrax™ consists of a hyperimmunogenic derivative, termed DNI (Dominant Negative Inhibitor), of recombinant protective antigen (rPA) 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.  PA is the principal determinant of protective immunity to anthrax. 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 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™, the DNI vaccine has also shown structural stability at temperatures as high as 70 degrees Celsius (158 degrees Fahrenheit).   Development work has been sponsored under a $9.4 million National Institute of Allergy and Infectious Disease (NIAID) grant enabling development of thermo-stable ricin and anthrax vaccines.  Soligenix believes that it will be able to develop VeloThrax™ with an efficacy profile superior to other anthrax vaccines.

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 National Institute of Allergy and Infectious Diseases (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.

SOURCE: Soligenix