By Grant Zeng, CFA · improved stability and shelf-life at temperatures exceeding 40ºC;
Soligenix Announces Positive Results for Combination Vaccine
On July 9, 2014, Soligenix (SNGX) announced positive results from a preclinical study of the combination of RiVax™ and VeloThrax™. The combination induces protective antibodies for both ricin toxin and anthrax toxin exposure.
Previously, Soligenix has demonstrated that each vaccine, when administered as a single vaccine, induced neutralizing antibodies for each toxin respectively. In this preclinical study, Soligenix further demonstrated that the combination of RiVax and VeloThrax induced neutralizing antibodies that were reactive against both toxins and these 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.
This study is sponsored under $9.4 million cooperative grant from the National Institute of Allergy and Infectious Diseases (NIAID). The results suggest that long-term immunity upon simultaneous vaccination can be achieved. This is important because both vaccines are developed for military usage and emergency first responders.
Soligenix plans to develop the combination vaccine using the company’s proprietary ThermoVax™ platform for stabilizing vaccines for stockpiling and for distribution of vaccines outside of normal cold chain requirements.
ThermoVax™: Vaccine Thermostability Platform Technology
ThermoVax is Soligenix’ proprietary platform technology, which is a novel method of rendering aluminum salt, (known colloquially as Alum), adjuvanted vaccines stable at elevated temperatures. Alum is the most widely employed adjuvant technology in the vaccine industry. Soligenix’s ThermoVax can provide:
· dried vaccine with desirable physical and immunogenic properties;
· preservation of native protein structure;
· potential applicability to other immunostimulatory compounds that would benefit from the effectiveness of subunit vaccines;
· potential for development of multivalent or combination vaccines (e.g., combination ricin-anthrax vaccine);
The value of ThermoVax™ lies in its potential ability to eliminate the need for cold-chain production, transportation, and storage for Alum adjuvanted vaccines. This would relieve companies of the high costs of producing and maintaining vaccines under refrigerated conditions. The WHO reported that 50% of all vaccines around the world are wasted which includes thermostability issues. This is due to the fact that most Alum adjuvanted vaccines need to be maintained at between 2 and 8 degrees Celsius and even brief excursions from this temperature range (especially below freezing) usually necessitates the destruction of the product or the initiation of costly stability programs specific for the vaccine lots in question. The savings realized from the elimination of cold chain costs and related product losses would in turn significantly increase the profitability of vaccine products. Elimination of the cold chain would also further facilitate the use of these vaccines in the lesser developed parts of the world. ThermoVax™ has the potential to facilitate easier storage and distribution of strategic national stockpile vaccines in emergency settings.
ThermoVax™ will further enable Soligenix to expand its vaccine development expertise beyond biodefense into the infectious disease space and also has the potential to allow for the development of multivalent vaccines (e.g., combination ricin-anthrax vaccine).
RiVax™ - Ricin Toxin Vaccine
RiVax™ is Soligenix’s proprietary aluminum-adsorbed vaccine developed to protect against exposure to ricin toxin, and is the first ricin vaccine.
The immunogen in RiVax™ induces a protective immune response in animal models of ricin exposure and functionally active antibodies in humans. The immunogen consists of a genetically inactivated subunit ricin A chain that is enzymatically inactive and lacks residual toxicity of the holotoxin.
Two Phase I human clinical trials have been completed. Results of the first Phase I human trial of RiVax™ established that the immunogen was safe and induced antibodies anticipated to protect humans from ricin exposure. The antibodies generated from vaccination, concentrated and purified, were capable of conferring immunity passively to recipient animals, indicating that the vaccine was capable of inducing functionally active antibodies in humans. The second trial (Phase Ib) evaluated a more potent formulation of RiVax™ that contained an aluminum adjuvant (Alum), was completed in September 2012. The results of the Phase Ib study indicated that Alum adjuvanted RiVax™ was safe and well tolerated, and induced greater ricin neutralizing antibody levels in humans than adjuvant-free RiVax™.
RiVax™ has been granted Orphan Drug designation by the FDA for the prevention of ricin intoxication. Assuming development efforts are successful for RiVax™; potential government procurement contract(s) could reach $200 million.
A Phase II study will be initiated with data available in 2H2015.
VeloThrax™ – Anthrax Vaccine
VeloThrax™ is Soligenix’s proprietary vaccine based on a recombinant Protective Antigen (rPA) derivative intended for use against anthrax. Soligenix has entered into an exclusive license option with Harvard College to license VeloThrax™ (also known as DNI for dominant negative inhibitor) for a vaccine directed at the prevention of anthrax infection of humans.
VeloThrax™ is a translocation-deficient mutant of PA with double mutations of K397D and D425K that impede the conformational changes necessary for endosomal membrane translocation into the cell cytoplasm. In the absence of that PA translocation step, anthrax toxin trafficking and function cease. VeloThrax™ is also considered a more immunogenic candidate than native rPA. This apparent increase in immunogenicity suggests that the DNI rPA is processed and presented to the immune system more efficiently by cellular antigen processing pathways, which is consistent with known properties of the molecule.
DNI versions of rPA such as VeloThrax™ are also capable of inducing antibodies that neutralize the activity of the anthrax toxin complex. Unlike fully-functional rPA, VeloThrax™ might be given to a patient post-exposure without risk of enhancing intoxication during an infection.
The overall objective of the VeloThrax™ program is to rapidly and efficiently develop a next generation anthrax vaccine which combines a well-established, safe and relatively low risk vaccine development and dosing approach with targeted, proven innovative strategies. VeloThrax™ will potentially be a combination of a stable, readily manufactured mutant rPA subunit antigen with next generation, clinically compatible adjuvants which have been demonstrated to enhance potency and reduce the time and number of vaccine doses required to achieve protective titer using a variety of vaccine antigens. This blend of proven yet innovative technologies will provide a safe and stable alternative to the existing licensed anthrax vaccine product. Soligenix also proposes to adapt newly developed glassification technology to enable a thermostable, dried, single vial, pre-formulated adjuvanted rPA vaccine which is suitable for both long term storage and field use without typical cold chain constraints.
Potential government procurement contracts could reach $500 million assuming development efforts are successful for VeloThrax™.
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· improved stability and shelf-life at temperatures exceeding 40ºC;