VIRUSMAX™

The Technology

Influenza vaccinations are critical to public health. The world influenza vaccine market is projected to be over US$7 billion and growing at an average rate of >20% per year. Last year, more than 500 million doses of vaccine were manufactured and used. All were derived from well-established egg-based production systems. Over the last several decades, numerous strategies have been employed in an attempt to increase the specific productivity of egg-based influenza vaccine manufacture. These include solvent extraction of influenza virus from infected allantoic fluid by multiple treatments, protein precipitation and ion exchange chromatography. However, in nearly all these methods allantoic fluid is pre-clarified before treatment and, as such, they ignore the potential for the presence of virus particles that may be physically associated with insoluble allantoic debris.

Microbix’ proprietary VIRUSMAX technology is a rapid, non-toxic technique for increasing the specific yield of multiple strains of influenza virus from the allantoic fluid of embryonated chicken eggs. Numerous studies have been performed in allantoic fluids from a wide variety of commercial and non-commercial sources. Liberation of intact insoluble debris phase-associated influenza virus, using strain-optimized extraction buffers, significantly augments viral yield. Such increases in viral yield can be can be used to increase the productivity of standard downstream influenza vaccine manufacturing processes.

Microbix VIRUSMAX technology has been shown to increase virus yields in numerous strains under numerous manufacturing scenarios (Hughes et al. Vaccine (2007) 25, 4456). The level of optimization varies by virus strain and type. Estimates of overall enhancement for a typical trivalent vaccine production are at least two-fold.

Microbix has been granted patents in the USA, Canada, Mexico, Argentina, Europe, Italy, India, Japan, Australia and China.

Commercialization Strategy

Microbix has chosen to license the VIRUSMAX technology on a regional basis, starting with countries where vaccine supply is most deficient. Licenses are initially available to local domestic manufacturers, multinational manufacturers with facilities in the licensing region, and/or de-novo facilities. The terms for such licenses are structured to include upfront and royalty payments.

Microbix created Crucible International Biotechnologies (CRIB) to implement VIRUSMAX commercialization strategy.

CRIB is a licensing, investment and management entity. Microbix has granted to

CRIB worldwide exclusive rights for VIRUSMAX. CRIB selects regional partners to build influenza vaccine facilities. Its contribution to the partnership includes exclusive regional licenses, initial management and investment in return for equity in the regional joint venture and royalty from sale of product. The Manufacturing Joint Venture (MJV) with Hunan Province is CRIB’s initial program.

China JV

The existing seasonal influenza vaccine market in China is currently small and under-developed, about 30 million doses going to only 2% of the target population, the majority of which is largely supplied by a collection of domestic manufactures that do not meet the quality standards of the western regulatory authorities. The objective of this venture is to bring increased supply of a world-class flu vaccine into new markets, at least 20% of target populations, identified by the Chinese Central Government to approach vaccination levels as recommended by the WHO.

• Microbix and the Hunan provincial government signed an agreement to form a joint venture in China to build and operate the country’s first domestically owned international standard flu vaccine facility (to US/EU standards) to manufacture VIRUSMAX optimized flu vaccine for the Chinese market
• Agreements in place for a phased approach to build 120 million dose capacity
• Engineering and design Feasibility Study completed
• The first stage will be the completion of a 20MM dose vaccine plant. The final stage will be the completion of a 100MM dose vaccine capacity.
• Sufficient capacity to enable China to embark for the first time on large scale flu vaccination programs comparable to other countries.
• An investment ‘in China for China’ with Chinese ownership and preferred supplier status
• Investment risk mitigated by a ‘phased’ approach
• Senior management has extensive experience in vaccine manufacturing and sales and marketing in China
• Microbix to make equity investments and oversee the establishment of the MJV
• This is China’s first international standard vaccine plant coincident with China government mandates to increase vaccine penetration by over ten fold.