In conversation with Ron Babecoff

As a co-founder of BiondVax Pharmaceuticals (TASE:BNDX), Ron Babecoff has led the Israeli developer of a universal flu vaccine since its inception in 2003. Prior to BiondVax, Dr. Babecoff was with Omrix Biopharmaceuticals as marketing manager, where he was involved in identifying West Nile Fever treatments and building cooperation with the NIH, and forming alliances with leading international pharmaceutical companies. He holds a Doctor of Veterinary Medicine degree from the University of Liège, Belgium and a Master in Entrepreneurship and Innovation from ISEMI, the Israeli branch of Swinburne University, Australia. In this interview with, Dr. Babecoff discusses the company’s development of a universal flu vaccine to provide multi-season and multi-strain protection against most human influenza virus strains, including both seasonal and pandemic flu strains, and its potential to revolutionize the flu vaccine industry.

Let’s start with a brief history of BiondVax.

Our technology originally was developed by Prof. Ruth Arnon and her team at the Weizmann Institute of Science in Israel. She based her research on the question, how can we make one vaccine effective against any flu strain? It was a very original way of thinking in the 1990s. Over the next 15 years, her research established the feasibility of a universal, peptide-based influenza vaccine in animals. With this technology and subsequent development at BiondVax, we became operational in 2005 and went public in Tel Aviv in June 2007.

Can you give us an influenza virus 101?

There are three types of influenza virus: A, B and C. Influenza A and B viruses are found in humans and animals, while C is found almost only in animals. The C type virus is rare in humans and usually causes a very mild disease. The B type virus is often limited to local outbreaks, and its surface proteins are considered to be relatively stable and are responsible of about 20% of flu disease in humans. Influenza type A and its many sub-types are the most common and are considered to be the major cause for widespread epidemics and pandemics, causing about 80% of flu illness. This is due to the frequent changes in their surface proteins, which the human immune system recognizes as foreign antigens. Minor changes in the surface proteins of the virus are termed antigenic drifts, while major changes in one or both of the surface proteins are known as antigenic shifts. The greater the change in the surface proteins, the less effective are the body’s immune defense and current vaccines.

Antigenic drifts and shifts trigger seasonal epidemics or worldwide pandemics, as we saw in 1918 with the Spanish flu, 1957 with the Asian flu, 1968 with the Hong Kong flu, 1976 with the Swine flu, 1977 with the Russian flu and 1997 with the Avian flu and recently in 2009 with the Swine flu. Pandemics may happen every decade, following a major antigenic shift and resulting from a cross species infection.

How does your technology work?

BiondVax’s universal flu vaccine, M-001, represents a quantum leap in the flu vaccine arena, as it is based on a proprietary combination of non-changing epitopes, or peptides, serving as a common denominator to practically all existing and future flu virus strains, including both seasonal and pandemic flu strains, such as the avian and swine flu. M-001 comprises a proprietary combination of nine peptides from influenza virus proteins, combined into a single recombinant protein and produced by fermentation in E.coli. The peptides were selected from HemAgglutinin, NucleoProtein and Matrix proteins in order to activate both humoral, or antibody, and cellular immunity. Hemagglutination inhibition is the current regulatory marker for flu vaccines.

How fast can you produce M-001?

The vaccine is a single recombinant protein and, because it is manufactured by fermentation in E. coli, it can be produced on an industrial scale in six-to-eight weeks, enabling year-round production and vaccination. For example, it took six months for a vaccine to be produced against the Swine flu outbreak in 2009. We were lucky that the last Swine flu outbreak was relatively mild.

What’s the potential of the vaccine?

M-001 has the potential to revolutionize the entire flu vaccine industry. The vaccine is not strain- or season-dependent. It has the potential to provide what, we believe, is three-to-five years of broad protection against existing and futureseasonal and pandemic influenza strains, including the highly pathogenic Avian flu. Moreover, a single formulation will, for the first time, enable year-round vaccination. With our vaccine, mass production planning will be possible as well as on-demand worldwide distribution.

What is the state of the vaccine against pandemic flu strains?

Earlier this year, we completed a series of biological and other tests that found our universal flu vaccine matched all six potentially pandemic flu strains in the world today, including H5N1, H5N8, H6N1, H7N7, H7N9 and H10N8. The tests compared the vaccine elements and the elements contained in new, potentially pandemic influenza strains, which have managed to infect humans, some of which are lethal. Our ongoing investigations found that the small pieces contained in our universal flu vaccine are a good match for all of these new strains. These small pieces are enough to teach our immune system to recognize all flu strains, so that the body quickly stops the virus from causing illness. Based on these findings, we believe the universal vaccine, when the development stage has been completed, will be broadly effective against present and future strains, compared with current vaccines that are strain-specific.

Can you review the clinical history of M-001?

In 2008, we began the first oftwo Phase 1/2 trials, BVX002 and BVX003, with 63 individuals, aged 18 to 49, and with 60 individuals, aged 55 to 75. In 2010, we began the first oftwo Phase 2 trials, BVX004, with 200 participants, aged 18 to 49, and BVX005, with 120 participants, aged 65 and older. The final trial concluded in 2012. That’s a total of more than 440 subjects. The vaccine had a positive safety profile in all age groups and induced both antibody and influenza-specific immune responses. In addition, our manufacturing facility successfully passed a European GMP audit in 2012. To the best of our knowledge, our universal flu vaccine is the most mature technology in the field of universal influenza vaccines, with the largest set of preclinical and clinical data.

What’s next in your clinical program?

We are planning an additional Phase 2 clinical trial in Israel this year and a larger one inEurope to start in 2015. Pivotal Phase 3 testing is still another two-to-three years away. We will likely require a strategic partner for the Phase 3 and we have had discussions in Europe and in the U.S., where we filed an IND in 2013.

What’s your model for pandemic preparedness?

Our business model is to engage in multi-year stockpiling agreements with health organizations and governments around the world for our universal vaccine as a pandemic primer vaccine. If the vaccine is given to people immediately after a pandemic flu outbreak, and then subsequently the conventional pandemic-specific vaccine is administered, the expected result would be that more people would be protected against a broader set of pandemicflu strains. The company considers this approach to have unique advantages because it would enable countries to be prepared right now, ahead of any flu outbreak, so that once the pandemic outbreak is official, governments could protect their people and keep their countries safe. We believe it is critical to achieve preparedness for a deadly pandemic flu ahead of an outbreak and that the universal vaccine can enable governments today to proactively protect their populations for when the pandemic flu breaks out.

Could you summarize your vaccine’s competitive edge?

Let me begin by saying that M-001 has an excellent safety profile, with four clinical trials in 440 people from young adults to the at-risk elderly. It triggers both arms of our immune defenses, is active without the need for an adjuvant, is easily, quickly and cheaply manufactured in only six-to-eight weeks, compared with conventional flu vaccines that take about six months, can be produced year-round and can be stockpiled as its composition does not change. Finally, M-001 has two indications: as a universal flu vaccine; and as an enhancer of conventional strain-specific seasonal and pandemic flu vaccines. This provides a new approach to pandemic preparedness ahead of any flu outbreak.