GREFFEX HAS BEEN EXPANDING ITS GREVAX TECHNOLOGY PLATFORM

December 1, 2014; February 1, 2015

The GreVax technology platform is built on the adenovirus (Ad). It is composed on two sets of components that can be modified independently: vector modules deleted of all Ad genes and packaging plasmids that deliver the packaging information. Greffex has established the feasibility of the GreVAX system with capsids of the prototypical Ad5 serotype. Fully deleting GreVAX vectors of all Ad genes minimizes interference caused by pre-existing immunity. It may nevertheless be beneficial to package GreVAX modules into capsids of other rare Ad serotypes.

Greffex uses Ad capsids of species C for its vaccine applications. This takes advantage of the high immunogenicity of these Ad serotypes. Greffex packages vectors designed for gene therapy into Ad capsids of species B. For these applications the Company takes advantage of lower intrinsic immunogenicity.

Greffex has broadened its GreVAX technology base. It can now match the design of its vectors to the immune status of the target population and to the intended therapeutic use.

GREFFEX HAS BEEN DEVELOPING BROAD BIOTERROR VACCINES

February 1, 2015

In North America and Europe approximately 940 million people are at risk of bioterrorism agents. According to the World Health Organization, its committee of experts’ estimates that an aircraft release of 50 kg of anthrax spores over an urban developed population of 5 million would result in about 250,000 deaths and an additional 125,000 would be severely incapacitated.

To protect major population centers, it will therefore be necessary to provide anthrax vaccines to a large segment of the population. In the US alone, billions of dollars have been budgeted for medical countermeasures to terrorism agents and to stockpile anthrax vaccines for a “three-city attack”. The problem with the presently available anthrax vaccine is its low immunogenicity. Several booster injections are required over a one-year period to establish immunity.

Greffex produced the anthrax vaccine GreANX based on its GreVAX Universal Platform. This anthrax vaccine has successfully undergone preclinical testing.

Another infectious agent with a bioterror threat potential similar to anthrax, is the plague. Greffex has been constructing the GrePla candidate vaccine as a single target vaccine that can be combined with GreANX for immunization. In parallel, Greffex has assembled GreVAX-based vaccine, GreAnPla, that carries antigens for anthrax and plaque on a single construct. This approach allows increased efficiency in manufacture and vaccination.

NIAID TESTS GREFFEX’S EBOLA VACCINE

February 1, 2015

A 1967 outbreak of the “Marburg” virus (MARV) first brought to light the dangers of viral hemorrhagic fevers caused by viruses of the filoviridae family. After an outbreak in 2012 a death from a MARV infection was recently noted in Uganda. Other members of the filovirus family, namely the Ebola viruses (EBOV), are even more lethal. The members of this genus are named after the location of their major outbreaks, Zaire (ZEBOV), Sudan (SEBOV), Reston, VA (RESTOV) and Cote d’Ivoire (CIEBOV). Numerous outbreaks of viruses have been observed in the last 40 years (WHO). The most devastating outbreak so far was caused by a mutated version of ZEBOV. It first appeared in December 2013 and has spread through several countries in Western Africa, Guinea, Sierra Leone, and Liberia. It has been spreading in an uncontrolled fashion and has led to several thousand infections and deaths (WHO). Travelers infected with the disease have reached Europe and the US leading to secondary transfers of the disease to nurses in Spain and the US (WHO). Neither therapeutic drugs nor vaccines are presently available to combat any of these infections.

In November 2014, Greffex initiated discussions with the National Institute of Allergy and Infectious Diseases (NIAID) about the construction of a GreVAX-based Ebola vaccine. Due to the earlier success with GreMERSfl and GreFluVie, Greffex was invited by NIAID to deliver an Ebola vaccine candidate to be tested in nonhuman primates. Greffex initiated the construction of its GreZEBm vaccine candidate. It was completed within one month. In parallel, the Company’s scientists developed a stringent testing protocol that took into consideration the medical realities found in Western Africa. Their goal was closely to approximate future clinical trials. In early February 2015, Greffex delivered its GreVAX-based GreZEBm vaccine to NIAID for these protective studies in NHPs.

NIAID TESTS GREFFEX’S AVIAN FLU (H5N1) VACCINE

January 9, 2015

In studies sponsored by the National Institute of Allergy and Infectious Disease (NIAID), Greffex’s GreFluVie vaccine proved to be highly effective in protecting animals against H5N1. Mice were immunized in a prime/boost schedule before being challenged with a lethal dose of the pandemic avian influenza virus. At the low dose of 3×108 genome equivalents, the vaccine proved to be highly effective when given by intramuscular, subcutaneous, and intranasal routes. Intramuscular injection resulted in a rate of survival of 100%.

NIAID TESTS GREFFEX’S MERS-CoV VACCINE

September 4, 2014

In the summer of 2014, Greffex was asked by the National Institute of Allergy and Infectious Diseases (NIAID) for a sample of its vaccine for MERS-CoV so that it could run tests to evaluate the production of neutralizing antibodies.

On a very tight schedule (less than two months) Greffex produced, purified, and vaccinated animals with the GreMERSfi. Mice were immunized in a prime/boost schedule with a small dose (approx. 3×108 genome equivalents).  A standard micro-neutralization assay was used to quantify the humoral immune responses. All of the animals raised significant levels of neutralizing antibodies. 75% of the animals presented with very high antibody titers in the range of 640 to more than 2,560 (the test limit).  In light of these results, the NIAID has invited Greffex to request further trials under its sponsorship.