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1 <p><b>Researching the Fight Against Infection</b></p>
2 <p>PLIVA's anti-infectives research is being conducted in three separate programs:
3 Macrolide research, New Antibiotics research, and Biodiversity discovery.</p>
4 <p>With its internationally acknowledged insight into macrolide chemistry, as
5 evidenced by its discovery of Azithromycin, PLIVA has entered into a strategic
6 co-operation with GlaxoWellcome (currently <a
7 href="http://www.gsk.com">GlaxoSmithKline</a>) to identify a novel macrolide
8 antibiotic for world-wide development and marketing. The goal of this venture
9 is to identify a macrolide with improved efficacy, particularly against resistant
10 strains of bacteria.</p>
11 <p align="center"><img src="p/OKrnd_ljudi_7.jpg" width="300" height="202" border=1></p>
12 <p>The goal of PLIVA's second program is to find a novel anti-bacterial compound
13 class showing no cross-resistance with current antibiotics. In cooperation with
14 <a href="http://www.althexis.com">Althexis</a>, Boston, USA, a company with
15 leading expertise in
16 structure-based drug
17 design and crystallography, researchers from both companies have identified
18 two novel scaffolds showing activity with <i>in vitro</i> and <i>in vivo</i>
19 models of infections. A derivatization program
20 to identify a developmental candidate within the shortest possible time has
21 been fully established.</p>
22 <p>As an extension of its anti-bacterial program, PLIVA has licensed-in a novel
23 anti-fungal compound (PLD-118) from <a href="http://www.bayer.com">Bayer
24 AG</a>, Germany. This compound has demonstrated
25 excellent efficacy against the most common systemic fungal infections as well
26 as excellent tolerability and pharmacokinetic properties in various pre-clinical
27 models. PLD-118 would represent the first novel, orally available compound class
28 for the treatment of infections caused by the Candida yeast since the introduction
29 of the azoles in the 1970s.The project has a novel mode of action and has strong
30 potential to solve azole resistance problems.</p>
31 <p>In the Biodiversity program, activities are being focused on generating the
32 "toolbox" for the generation of novel enzymes and the application of the technology
33 to streptomyces, one of the most important microbial organisms for the production
34 of small molecules. Significant improvement of the general technology, which
35 is currently patented, has been achieved. The Biodiversity program is conducted
36 in both MIXIS France and PLIVA Zagreb laboratories, and it should give MIXIS
37 a vehicle for future products, a far longer patent protection and simplified
38 and attractive format. </p>

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