Millenia Hope Inc. (fka MLHI)

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Grant 5U19AI073975-02 from National Institute Of Allergy And Infectious Diseases IRG: ZAI1

Abstract: HIV reverse transcriptase (RT) has been an attractive target for HIV drug development, with 11 of the 20 approved drugs targeting RT DMA polymerase activity. However, HIV drug resistance is an increasingly serious clinical problem. New therapeutics are needed, especially those against unaddressed HIV targets, such as HIV RT-associated RNase H (RNH). RNH is underexplored for antiviral therapeutic discovery and development, and very few RNH inhibitors (RNHI) have been identified. This research program, HIV RNase H Natural Product Inhibitors, builds on a novel technology for plant cell culture as a source of novel antiviral agents. We have already identified several natural product RNHI with submicromolar antiviral activity. The proposed studies comprise three projects designed to develop and optimize these and other compounds to be identified from screening an existing 160,000 product library. The iterative research and development program combines the efforts of several investigators from academia and industry with considerable experience in HIV drug discovery and development. Project 1, Isolation and Optimization (Baroudy, Project Leader, Millenia Hope Inc) will isolate and purify natural products from plant cell cultures and carry out semisynthetic optimizations based on SAR developed in the other projects. Project 2, Biochemistry and Virology (Parniak, Program Director, University of Pittsburgh) will characterize the compounds for biological activity to generate data for use in SAR development, conduct detailed mechanism of action analysis, and screen the product library for new RNHI chemotypes. Project 3, Structural and Computational Biology (Arnold, Project Leader, CABM/Rutgers) will determine structures of RT complexed with RNHI for use along with data from Project 2 to develop an SAR to predict modifications to improve potency. Such modifications will be made in Project 1, then characterized in Projects 2 & 3. This iterative process will continue until 2-3 lead candidates and 4-6 backups with low nM potency have been selected to enter extensive preclinical assessment. The research program will have significant impact on public health by developing new anti-HIV therapeutics for use in the treatment of patients infected with HIV strains resistant to the current clinically used drugs

Keywords: biological product

Project start date: 2007-03-05

Project end date: 2012-02-29

5U19AI073975-02 (2008): $896645


zu:

http://www.newswire.ca/en/story/63717/millenia-hope-inc-rece…

"Millenia Hope Inc receives a grant from the National Institutes of Health (USA) to develop new HIV therapeutics in consortium with the University of Pittsburgh and Rutgers University

WILMINGTON, DE, and MONTREAL, April 19 /CNW Telbec/ - Millenia Hope Inc.,
(MLHP.PK - Frankfurt: MLF.F) in consortium with the University of Pittsburgh
and Rutgers University has been selected by the National Institutes of Health
(USA) to receive more than $4.6 M over the next five years for a project "HIV
RNase H natural product inhibitors" to develop novel HIV therapeutics directed
at the under-explored HIV target ribonuclease H (RNase H). This research
program is driven by Phytomics, a unique technology of Millenia Hope Inc., for
the production and isolation of plant cell culture-derived natural products to
inhibit HIV RNase H, a viral target that is essential for HIV-1 replication
but for which there are no drugs in current clinical development.
The NIH award will support the efforts of an outstanding group of
internationally-recognized investigators from three institutions. Dr. Michael
A. Parniak, Professor of Molecular Genetics & Biochemistry at the University
of Pittsburgh and Principal Investigator of this multi-team research effort,
has nearly 20 years experience in HIV research and is regarded as a thought
leader in the discovery of drugs targeting HIV RNase H. Dr. Parniak notes
"This project has an excellent probability of discovering new HIV
therapeutics. The research team we have assembled is world-class, and Millenia
Hope's Phytomics technology provides not only a unique but a readily renewable
resource for the discovery and production of novel HIV drugs."
Dr. Bahige M. Baroudy, President and CSO, Millenia Hope Inc., has
extensive experience in development of new HIV therapeutics and was among the
first to validate HIV entry as a therapeutic target. Structural biologist
Dr. Eddy Arnold at Rutgers is one of the most highly cited HIV research
scientists. Dr. Ronald Levy at Rutgers has developed unique computational
methods to assist in design of new drug entities. The ultimate goal of the
group is to develop a new class of HIV therapeutics that will be effective
against the increasingly prevalent viral strains that are resistant to current
drug therapies.
Dr. Baroudy noted, "Millenia Hope is honored that NIH recognizes our
Phytomics technology as a source for novel HIV therapeutics. The NIH support
and the willingness of world-class scientists; Drs. Parniak, Arnold and Levy
to collaborate with us in the development of new drugs for the treatment of
HIV infection is an excellent validation of of our Phytomics technology and
our R&D programs." Dr. Baroudy also stated "Millenia Hope's accomplishments
are a tribute to the sound scientific infrastructure in the Province of
Quebec, Canada. We are also indebted to our shareholders who supported us over
the years, especially in acquiring the patent in 2006 that describes the
compounds that inhibit HIV RNase H. This collaborative research project with
Drs. Parniak, Arnold and Levy will realize our objective of developing a new
therapy for HIV." vom April 19, 2007 8:38 AM