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Soligenix Receives European and Canadian Patents for Ricin Toxin Vaccine

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Soligenix, Inc. announced on July 9 that it has received notice of allowance for European and Canadian patent applications further extending protection around ThermoVax® including coverage of the Company’s ricin toxin vaccine, RiVax®.

RiVax® is Soligenix’s proprietary heat stable recombinant subunit vaccine developed to protect against exposure to ricin toxin. ThermoVax® is a proprietary vaccine heat stabilization platform technology and the patent, titled “Thermostable vaccine compositions and methods of preparing same,” has been previously allowed in Japan, Australia and New Zealand with applications pending in China, United States (US) and other worldwide jurisdictions.

Ricin toxin is a lethal plant-derived toxin and potential biological weapon because of its stability and high potency, and the fact it is readily extracted from by-products of castor oil production.  The U.S. Centers for Disease Control and Prevention estimates that the lethal dose in humans is about the size of a grain of salt.

The issued patent is complementary to previous patents, including US patents 8,444,991 granted on May 21, 2013 and 8,808,710 granted on August 19, 2014, that include claims for methods of making stabilized vaccines and their attendant compositions. In this new patent, the main claims cover formulations of Soligenix’s proprietary thermostabilized ricin toxin vaccine, RiVax®.

The thermostable formulation of RiVax® has been shown to be stable for at least 12 months at temperatures up to 40 degrees Celsius (104 degrees Fahrenheit) and to provide 100% protection to non-human primates exposed to aerosol ricin challenge in preclinical studies.

Recent developments in the RiVax® program have also described immune correlates of protection for the ricin toxin vaccine, which are important to facilitating potential approval of thermostabilized RiVax® via the US Food and Drug Administration (FDA) “Animal Rule”. As a biodefense vaccine, RiVax® also has the potential to qualify for a priority review voucher (PRV) upon FDA approval.

RiVax® contains a genetically altered version of a Ricin Toxin A (RTA) chain containing two mutations that inactivate the 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 subsequently 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.  Vaccination with the thermostabilized Alum-adjuvanted RiVax® formulation in a large animal model provided 100% protection (p<0.0001) against acute exposure to aerosolized ricin, the most lethal route of exposure for ricin.  The protected animals also had no signs of gross lung damage, a serious and enduring ramification with long-term consequences for survivors of ricin exposure.

The development of RiVax® has been sponsored through a series of grants from both National Institute of Allergy and Infectious Diseases (NIAID), and the FDA and ongoing development is sponsored by NIAID contract #HHSN272201400039C.  The Phase 2 clinical trial planned for the second half of 2018 is contingent upon exercise of the final option by the US government under NIAID contract #HHSN272201400039C and/or through other funding sources. RiVax® potentially would be added to the Strategic National Stockpile and dispensed in the event of a terrorist attack.  RiVax® has received orphan drug designation in the United States and in Europe.

As a new chemical entity, an FDA approved RiVax® vaccine has the potential to qualify for a biodefense PRV, which allows the holder accelerated review of a drug application.  Approved under the 21st Century Health Cures Act in late 2016, the biodefense PRV is awarded upon approval as a medical countermeasure when the active ingredient(s) have not been otherwise approved for use in any context.  PRVs are transferable and can be sold, with sales in recent years ranging between $125 million to $350 million.  When redeemed, PRVs entitle the user to an accelerated review period of six months, saving a median of seven months’ review time as calculated in 2009.  However, the FDA must be advised 90 days in advance of the use of the PRV and the use of a PRV is associated with an additional user fee ($2.7 million in 2017).

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