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Welcome to the presentation of Lars Kattner Endotherm Life Science Molecules Science Park 2 66123 Saarbrcken Germany 1 Location Our facilities are favorably located on the campus of the Universitt des Saarlandes, Saarbrcken

  1. Welcome to the presentation of Lars Kattner Endotherm Life Science Molecules Science Park 2 66123 Saarbrücken Germany 1

  2. Location Our facilities are favorably located on the campus of the Universität des Saarlandes, Saarbrücken Consequently we have, besides our own facilities and personnel, access to additional • state-of-the-art technical equipment • modern analytical instrumentation • scientific expertise 2

  3. Products >3000 „Inhouse-made“ research chemicals for the Life Sciences • Compound libraries • Fluorescent probes • Vitamin D metabolites, steroids, partly labeld (D, 13 C) • Coenzyme A esters • Optogenetics: synthetic retinal analogs • Stable isotopes • Pharmaceutical substances (active pharmaceutical ingredients up to 100g, intermediates, impurities 3

  4. Highlighted Product Classes CCF4-AM DIFMUP HMG-CoA Fluorescent probes Coenzyme A ester OH OH HO OH HO Zonisamid-15N d4 Ethosuximid-13C, d3 Calcitrio l 25-Hydroxyvitamin D2 Stable isotopes Vitamin D metabolites 4

  5. Service Contract research, exclusive synthesis of research chemicals for • Drug discovery: screening compounds, libraries, building blocks • Diagnostics: biomarkers, labeled reagents, fluorescent probes • API-filing: reference standards, impurities, API laboratory samples 5

  6. Synthetic Expertise • Heterocyclic Chemistry • Pd catalyzed reactions (Heck, Sonogashira, Suzuki etc.) • Steriod/Vitamin D chemistry • Natural product synthesis • Stereoselective synthesis 6

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  8. Soft Skills > Additional capacity > High scope of resources concerning equipment and staff > State-of-the-art facilities > High safety standard > Moderate costs > Highly skilled scientific staff > Access to expertise which may not be available in-house > Professional project management > Commitment to quality > High confidentiality (protection of your IP) > Focused on timelines > Realistic match of expectations > Quick response to inquiries and immediate feedbacks > Speedy and pragmatic contract negotiations > Constant availability to talk about changes/problems/hurdles > Professional communication and reporting > High flexibility, ability to respond quickly to changing conditions > Proven track record 8

  9. 5 Good Reasons 1. Inhouse-made compounds („Made in Germany“) 2. Scientific Excellence 3. Efficient Communication 4. Quality Management 5. Innovative for already 30 years, proven track record 9

  10. Customers 20 projects 6 libraries (10-30 compounds each) 35 projects 14 building blocks and (API´s, 50-100g each) reference compounds > 300 steps 8 projects (steroids, 11 projects 13 projects benzodiazepines, (libraries,building blocks and 5 libraries (>100 compounds, steroid mimetics) reference compounds overall >100 steps >300 steps) > 200 steps, 4 FTE´s over 2 years 6 building blocks (6-8 steps each) 10

  11. Research Projects: New Inhibitors of MurA, an Antibacterial Target Enzyme Cross-linking, murein-structure MIC [µg/ml] Cell wall C 55 - Carri ESBL er Ps. OH UDP -N -Acetyl- MS MR E. - O Cytoplasma H O UNAG + Code aerug muraminacid- H 3 C O SA SA coli Klebs NH O UDP C 55 H pentapeptide O . O iella MurC- L-Ala D-Glu L-Lys D-Ala D-Ala F PI120 4 4 4 16 2 O 3 PO COO PEP NADPH+H + NADP + OH OH OH PI129 16 16 16 >32 8 O O O H O H O H O H 3 C H O O O NH O UDP NH O UDP NH O UDP MurA MurB H O O O COOH COOH PI131 2 2 2 16 4 UDP-N-Acetylglucosamine Enolpyruvyl-UNAG UDP-N-Acetyl- (UNAG) (EP-UNAG) Muramin acid (UNAM) Scholz T, Heyl CL, Bernardi D, Zimmermann S, Kattner L,Klein CD: Chemical, biochemical and microbiological properties of a brominated nitrovinylfuran with broad-spectrum antibacterial activity. Bioorg Med Chem. 2013;21:795-804. 11

  12. Research Projects: Development of pharmacological compounds to prevent R y R 2 mediated intracellular Ca 2+ leak and to stabilize SERCA mediated Ca 2+ uptake to inhibit arrhythmia trigger mechanisms 12

  13. Research Projects: Optogenetics . 13

  14. Research Projects: Synthesis of Vitamin D metabolites Kattner L, Volmer DA. Chapter: Synthesis of low abundant vitamin D metabolites and assaying their distribution in human serum by liquid chromatography-tandem mass spectrometry (LC- MS/MS) as a new tool for diagnosis and risk prediction of vitamin D related diseases. In: Gowder S, editor. A critical evaluation of vitamin D - basic overview, 1st ed. Rijeka: Intech publishers; 2017. P. 103-127. ISBN 978-953-51-3084-0. 14

  15. Thank you for your attention Lars Kattner, Ph.D., CEO Endotherm GmbH Science Park II 66123 Saarbrücken Germany Phone: ++49-(0)681-3946-7570 Fax : ++49-(0)681-3946-7571 E-Mail: info@endotherm.de www.endotherm-lsm.com 15

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