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IDRI and Medicago report positive results for Phase I clinical trial for an H5N1 vaccine

All 3 configurations of adjuvant and route of administration exceeded the 3 CHMP criteria

2013-04-18
(Press-News.org) SEATTLE, WA, and QUEBEC CITY, QC, April 17, 2013 – IDRI (Infectious Disease Research Institute), a Seattle-based non-profit research organization that is a leading developer of adjuvants used in vaccines combating infectious disease, and Medicago Inc. (TSX: MDG; OTCQX: MDCGF), a biopharmaceutical company focused on developing highly effective and competitive vaccines based on proprietary manufacturing technologies and Virus-Like Particles (VLPs), today reported positive interim results from a Phase I clinical trial for an H5N1 Avian Influenza VLP vaccine candidate ("H5N1 vaccine"). The results were announced at the World Vaccine Congress in Washington, DC. The H5N1 vaccine was found to be safe and well-tolerated and induced a solid immune response exceeding the three CHMP (Committee for Medicinal Products for Human Use) immunogenicity criteria for licensure of influenza vaccines. The vaccine was tested in three different configurations: using IDRI's Glucopyranosyl Lipid A ("GLA") formulated adjuvant, given both intramuscularly and intradermally, and using alum intramuscularly. All three configurations exceeded the CHMP criteria.

"These positive U.S. clinical trial results confirm that our H5N1 vaccine candidate is the best in class in our opinion, positioning Medicago as a significant player in the global pandemic market. The robustness of our H5N1 vaccine coupled with our rapid speed of production, offers a vastly improved solution in preparing for and managing potential pandemics. We also believe that our H5N1 vaccine with alum is the only alum-adjuvanted pandemic vaccine to achieve the three CHMP immunogenicity criteria," said Andy Sheldon, President and CEO of Medicago. "Moreover, the combination of our vaccine candidate with IDRI's adjuvant generated a robust immune response. In the case of a pandemic, governments will require the rapid development of an effective vaccine within their borders to conquer the spread of the virus, with our cost-effective and capital inexpensive system we are perfectly poised to obtain this objective. In summary, all three configurations tested of the H5N1 vaccine meet the CHMP criteria for licensure, placing us in a strong position with multiple product options. We will further investigate the use of alum and formulated GLA in a Phase II trial to be initiated in May 2013 with results expected in Q3 2013."

The trial results also underscore IDRI's leadership position in the field of adjuvants, with a focus on developing products that will reduce the burden of global infectious disease. "This study design and results demonstrate the potential for significant 'dose-sparing' -- increasing the number of available doses by reducing the amount of vaccine needed per individual, in a simple to administer format," said Dr. Steven Reed, IDRI Founder, President and Chief Scientific Officer, who presented the trial results at the World Vaccine Congress, along with Dr. Brian Ward, Professor of Medicine & Microbiology, McGill University, member of Medicago's scientific advisory committee and Medical Officer. "This H5N1 vaccine candidate represents the next generation of flu vaccines, combining our adjuvant technology with Medicago's rapid VLP technology and the intradermal delivery device from NanoPass."

Study Design

The Phase I clinical trial, which commenced in September 2012, enrolled 100 healthy adult volunteers, aged 18-49 years, at three locations in the U.S., testing for safety and immune response. The vaccine was also tested in comparison to Medicago's H5N1 vaccine with alum. The trial is funded by a multi-million dollar grant IDRI received from the Defense Advanced Research Projects Agency (DARPA), a division of the United States Department of Defense, to investigate the safety and immunogenicity of a novel adjuvant with a Nicotiana benthamiana produced vaccine candidate. Each study participant in the trial received two doses of a given formulation in order to collect and compare data.

The trial focused on evaluating the safety and immunogenicity of the H5N1 vaccine, combined with IDRI's GLA adjuvant, which has been exclusively licensed to Immune Design Corp for certain fields, including influenza. The vaccine was administered intramuscularly or intradermally. The intradermal route of administration was also tested in comparison with intramuscular delivery, using an FDA licensed device (MicronJet600®, NanoPass Technologies) as the micro-needle device was previously shown in seasonal and pandemic flu tests to allow significant dose sparing. This study is among the first to test intradermal adjuvants and is the first time GLA has been tested intradermally.

Safety and Immunogenicity Results

The H5N1 vaccine candidate has been tested in over 300 healthy volunteers to date, none of which have experienced any serious adverse reactions. The H5N1 vaccine candidate was found to be safe and well tolerated. As planned in the clinical design, monitoring of adverse events will continue for one year.

All three configurations of adjuvant and route of administration for 20ug of the H5N1 vaccine candidate induced a solid immune response against the H5N1 viral strain that exceeded the CHMP immunogenicity criteria for licensure of influenza vaccines which are 40% seroconversion, 70% seroprotection and 2.5x geometric mean increase (GMI). For a 20ug dose of the H5N1 vaccine plus; 2.5ug GLA-AF administered intradermally (ID), 2.5ug GLA-AF delivered Intramuscularly (IM) and 0.5ug alum formulation administered IM, a four-fold increase in HI titers (seroconversion) was observed in 65.0%, 80.0% and 83.3% of subjects, respectively. The seroprotection rate was 70.0%, 85.0% and 89.9%, respectively. The GMI was 10.3x, 8.7x, and 11.4x, respectively.

About H5N1

According to the Centers for Disease Control and Prevention, the highly pathogenic avian influenza A (H5N1) virus is a deadly virus that occurs mainly in birds including domestic poultry. Though relatively rare, sporadic human infections with this virus have occurred and caused serious illness and death. Because of the unpredictability of pandemic flu, efforts are being made to create and stockpile a vaccine to combat H5N1 that reduces the amount of vaccine needed per person and can be easily administered.

About Medicago's pandemic flu vaccine candidate

Medicago's H5N1 vaccine candidate was formulated to protect against the Indonesian influenza virus. It is manufactured in Nicotiana benthamiana, a relative of the tobacco plant, using the Company's proprietary VLP technology. VLPs may have several advantages over traditional flu vaccines. They are made to look like a virus, allowing them to be recognized readily by the body's immune system, however, they lack the core genetic material making them non-infectious and unable to replicate. Medicago's technology only requires the genetic sequence of a viral strain and not the live influenza virus. This key difference allows vaccines to be manufactured within four weeks of obtaining the genetic sequence of a pandemic strain. This is in contrast with current manufacturing technologies which rely on strain adaptation and can only deliver a vaccine six months after a pandemic is declared.

INFORMATION:

About IDRI

IDRI is a Seattle-based non-profit organization committed to applying innovative science to the research and development of products to prevent, detect, and treat infectious diseases of poverty. By integrating capabilities, IDRI strives to create an efficient pathway bringing scientific innovation from the lab to the people who need it most. For more information, go to http://www.idri.org.

About Medicago

Medicago is a clinical-stage biopharmaceutical company developing novel vaccines and therapeutic proteins to address a broad range of infectious diseases worldwide. The Company is committed to providing highly effective and competitive vaccines and therapeutic proteins based on its proprietary VLP and manufacturing technologies. Medicago is a worldwide leader in the development of VLP vaccines using a transient expression system which produces recombinant vaccine antigens in plants. This technology has potential to offer more potent vaccines with speed and cost advantages over competitive technologies, enabling the development of a vaccine for testing in approximately one month after the identification and reception of genetic sequences from a pandemic strain. This production time frame has the potential to allow vaccination of the population before the first wave of a pandemic, and supply large volumes of vaccine antigens to the world market. Medicago also intends to expand development into other areas such as biosimilars and biodefense products where the benefits of our technologies can make a significant difference. Additional information about Medicago is available at http://www.medicago.com.

About NanoPass Technologies Ltd.

NanoPass is the developer of MicronJet600™, an FDA-registered intradermal microneedles device. NanoPass has concluded the world's first intradermal pandemic (H1N1) flu vaccine clinical study and additional seasonal flu studies, demonstrating equivalent or superior immunogenicity to standard intramuscular delivery using only 20% of the dose.

Forward Looking Statements

This news release includes certain forward-looking statements or forward-looking information for the purposes of applicable securities laws and such statements and information are based upon current expectations, which involve risks and uncertainties associated with Medicago's business and the environment in which the business operates. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking, including those identified by the expressions "anticipate", "believe", "plan", "estimate", "expect", "intend", and similar expressions to the extent they relate to Medicago or its management. The forward-looking statements are not historical facts, but reflect Medicago's current expectations regarding future results or events. Such statements include but are not limited to statements about the collaboration with IDRI and the Phase I clinical trial. These forward-looking statements are subject to a number of risks and uncertainties that could cause actual results or events to differ materially from current expectations, including the matters discussed under "Risk Factors and Uncertainties" in Medicago's Annual Information Form filed on March 28, 2013, with the regulatory authorities. Medicago assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those reflected in the forward-looking statements.

Contact:
IDRI
Lee Schoentrup
Director of Communications
(206) 858-6064

Medicago
Andy Sheldon
President/CEO
(418) 658-9393

Christina Cameron
Investor Relations
(418) 658-9393 ext.156

NanoPass
Yotam Levin
CEO
(972) 52-339-2727
yotam@nanopass.com

END



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[Press-News.org] IDRI and Medicago report positive results for Phase I clinical trial for an H5N1 vaccine
All 3 configurations of adjuvant and route of administration exceeded the 3 CHMP criteria