Novartis and collaborators discover new dual-acting class of antimalarial compounds with potential to both prevent and treat malaria infections

11/17/2011, 8:01 PM (Source: GlobeNewswire)

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Novartis and collaborators discover new dual-acting class of antimalarial
compounds with potential to both prevent and treat malaria infections
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* A new class of antimalarial drug candidates inhibits malaria parasite liver-
and blood-stages in malaria models
* Most current malaria treatments target blood infections but researchers
believe both liver and blood infections need to be treated to eliminate
malaria
* Data made publicly available to facilitate global discovery efforts
* Over the past decade, Novartis has delivered over 400 million doses of its
anti-malarial treatment Coartem(®) without profit, to more than 60 malaria-
endemic countries for public sector use


Basel, November 17, 2011 - The discovery of a new class of dual-acting
antimalarial compounds - the imidazolopiperazines (IZPs) - was published in the
journal Science online, at the Science Express website today[1]. The findings
report on compounds that target both liver and blood infections, attacking the
Plasmodium parasite at both stages in its reproduction cycle.

The findings describe how scientists developed a novel assay to determine liver
stage activity of candidate small molecules, then used the assay and other tools
to identify and optimize a chemical scaffold with activity on both blood- and
liver-stage parasites in malaria mouse models. Several other compound classes,
also with dual activity, are described and released by Novartis through ChEMBL -
Neglected Tropical Disease at https://www.ebi.ac.uk/chemblntd.

"For over a decade, Novartis has engaged in the front ranks of combating
malaria, pioneering the not-for-profit supply of our antimalarial treatment
Coartem(®) to the public sector of endemic countries," commented Joseph Jimenez,
CEO of Novartis. "These new findings further demonstrate our innovative and
sustainable research commitment in this important area which has become integral
to our corporate strategy for social responsibility."

Scientists from the Novartis Institutes for BioMedical Research (NIBR), through
the Genomics Institute of the Novartis Research Foundation (GNF) and the
Novartis Institute for Tropical Diseases (NITD), collaborated with the Scripps
Research Institute and Swiss Tropical and Public Health Institute. Research was
supported by the Wellcome Trust, Singapore Economic Development Board, and
Medicines for Malaria Venture. This is the second new class of antimalarials
discovered by the same group in the last two years and holds promise as a next-
generation treatment for malaria if confirmed.

"Novartis is committed to the elimination of malaria. Programs with our current
anti-malarial treatment have helped save more than one million lives[2] to date,
but there remains much to be done," said Mark Fishman, NIBR President. "Concerns
of potential future resistance to current medicines, and the need to treat liver
forms of malaria, propel our scientists to devise new medicines. The chemical
data from this successful study, and the methods of chemical analysis, have all
been released to the public domain. Hopefully, such sharing will facilitate
broad-based discovery efforts across the globe towards elimination of this
disease."

Researchers believe that future antimalarials will need to work against both
blood and liver stages to bring us closer to the goal of eliminating malaria
globally. The malaria parasite first infects the liver before moving to red
blood cells and causing symptoms. However, after clearance in the blood,
reservoirs of parasites can linger in the liver causing relapse and hampering
efforts toward complete elimination of the disease. Each year there are about
250 million cases of malaria and nearly one million deaths - mostly among
children living in Africa[3].

It is important to develop new classes of treatment that are one step ahead of
the parasite should parasite resistance to current therapies occur, according to
researchers. In collaboration with research partners, NIBR is working on
developing a pipeline of potential new treatment candidates for drug-resistant
malaria. Last year's development of the spiroindolone class, represented by
NITD609[4], is now in Phase I human clinical trials, with Phase II expected to
commence in early 2012.

"Compounds with dual activity are rare among current antimalarials," said Martin
Seidel, GNF Institute Director.  "The activity of the IZP compound class on
liver-stage parasites, if it can be confirmed in clinical trials, gives promise
to this class as a first-line therapy for the prevention and treatment of
malaria."

According to Elizabeth Winzeler, GNF Department Head and lead investigator,
"Little was known about malaria liver stages when we started this work and as a
consequence, we didn't have a good idea about how to approach the problem.
Eventually we decided to develop an automated microscopy method to look for
compounds that would alter the appearance of the developing liver stages. We are
excited that by publishing the full set of compounds active in both blood and
liver stages, new targets might be identified."

Broader commitment to fighting malaria: Novartis Malaria Initiative
This research is part of a broader commitment by Novartis in the fight against
malaria. The Novartis Malaria Initiative is one of the pharmaceutical industry's
largest access-to-medicines programs, focused on treatment, access, capacity-
building and research & development. Over the last decade, the initiative has
delivered over 400 million treatments without profit to the public sector, in
more than 60 countries, and has helped save more than one million lives[2].
Novartis believes that increasing access to medicines in developing countries is
not just a matter of buying medicines and distributing them, it also requires
bringing together good clinical practice, logistics management and other
expertise to ensure a long-term sustainable approach to improving health. For
more information visitwww.malaria.novartis.com.
Disclaimer
The foregoing release contains forward-looking statements that can be identified
by terminology such as "potential," "promise," "committed," "future," "will,"
"expected," "might," "commitment," "strategy," or similar expressions, or by
express or implied discussions regarding the potential development of new
antimalarial medicines, or potential future revenues from such antimalarial
medicines. You should not place undue reliance on these statements. Such
forward-looking statements reflect the current views of management regarding
future events, and involve known and unknown risks, uncertainties and other
factors that may cause actual results to be materially different from any future
results, performance or achievements expressed or implied by such statements.
There can be no guarantee that any new antimalarial medicines will be developed
and brought to market, or that Novartis will earn any revenues from any such
medicines.  In particular, management's expectations could be affected by, among
other things, unexpected research results or delays; unexpected clinical trial
results, including unexpected new clinical data and unexpected additional
analysis of existing clinical data; unexpected regulatory actions or delays or
government regulation generally; the impact that the foregoing factors could
have on the values attributed to the Novartis Group's assets and liabilities as
recorded in the Group's consolidated balance sheet, and other risks and factors
referred to in Novartis AG's current Form 20-F on file with the US Securities
and Exchange Commission. Should one or more of these risks or uncertainties
materialize, or should underlying assumptions prove incorrect, actual results
may vary materially from those anticipated, believed, estimated or expected.
Novartis is providing the information in this press release as of this date and
does not undertake any obligation to update any forward-looking statements
contained in this press release as a result of new information, future events or
otherwise.

About Novartis
Novartis Institutes for BioMedical Research (NIBR) is the global pharmaceutical
research organization for Novartis. NIBR's research network is comprised of more
than 6,000 scientists, physicians and business professionals working together
across more than ten locations to discover innovative medicines to treat
diseases with high unmet medical need. GNF is located in San Diego, CA; NITD is
in Singapore. For more information, please visithttp://www.nibr.com

Headquartered in Cambridge, MA, NIBR is an affiliate of Novartis AG, which
provides innovative healthcare solutions that address the evolving needs of
patients and societies. Headquartered in Basel, Switzerland, Novartis offers a
diversified portfolio to best meet these needs: innovative medicines, eye care,
cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools,
over-the-counter and animal health products. Novartis is the only global company
with leading positions in these areas. In 2010, the Group's continuing
operations achieved net sales of USD 50.6 billion, while approximately USD 9.1
billion (USD 8.1 billion excluding impairment and amortization charges) was
invested in R&D throughout the Group. Novartis Group companies employ
approximately 121,000 full-time-equivalent associates and operate in more than
140 countries around the world. For more information, please visit
http://www.novartis.com.

Novartis is on Twitter. Sign up to follow @Novartis at
http://twitter.com/novartis.

References
[1]Imaging of Plasmodium liver stages to drive next generation antimalarial drug
discovery. Science Express, Nov. 17, 2011. Copies of paper available to
reporters through scipak@aaas.org
[2] Estimate based on the ratio between annual malaria cases and deaths
published in the WHO World Malaria Report, a distribution analysis of the
cumulatively supplied artemether-lumefantrine treatments over time and the
efficacy rate of artemether-lumefantrine as per published clinical trial data.
[3] World Health Organization,World Malaria Report 2010. P 60.
[4]http://www.sciencemag.org/content/329/5996/1175.abstract

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Novartis Media Relations



Beth Calitri Mariellen Gallagher
Novartis Global Media Relations Novartis Institutes for BioMedical Research
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