COMPANY PROFILE PARTNER FOR COOPERATION VUOS Where

COMPANY PROFILE PARTNER FOR COOPERATION VUOS

Where you can find us 2 2 VUOS – PARTNER FOR COOPERATION

VUOS ownership 3 AGROFERT HOLDING, a. s. 3 100% VUOS – PARTNER FOR COOPERATION SYNTHESIA, a. s. VUOS, a. s. 100%

History 4 r ch ar e ti da n ou F 1941 4 s Re of on La o at or b e – n io OS am a riv P r e h uc Vo 1992 VUOS – PARTNER FOR COOPERATION h nt y f S tio lia ffi s R ia´ o n u er ht g a d A 10 1997 2004 0% m co a sia he &D es t isa t VU n ew N 1952 . s. ies f nt Sy pa o ny

VUOS main businesses 1. R&D and Production of Fine Chemicals 2. Toxicology and Analytics 5 10 6 14 70 Employees 5 VUOS – PARTNER FOR COOPERATION Sales in %

The Certificates of VUOS • Certificate ČSN EN ISO 9001: 2009 (organic chemicals - syntheses development and manufacture) • Certificate of Good Manufacturing Practice • Certificates of Good Laboratory Practice in Test Facility (OECD GLP Principles - 1997) • 6 Certificate of Accredited Certification Body for Certification of Products (EN 45011: 1998) • Certificate of Accredited Testing Laboratory (EN ISO/IEC 17025: 2005) 6 VUOS – PARTNER FOR COOPERATION

Strong Points • Education structure of employees • VUOS is located in area of long-lasting chemical tradition and complete infrastructure • Cooperation with University of Pardubice 7 Skilled – 25 % Secondary – 30% University degree – 36% Ph. D. degree – 9% 7 VUOS – PARTNER FOR COOPERATION

R&D, upscaling • Pharmaceutical intermediates also under GMP standard 8 • Intermediates for microelectronics • Custom syntheses of chemical specialities • Dyes and pigments for special application 8 VUOS – PARTNER FOR COOPERATION GMP certificate

R&D, upscaling Wide range of quantities Grams – in laboratory 9 Kilograms – in kilolab unit Metric tons – in VUOS production plant Hundreds of MT – 9 VUOS – PARTNER FOR COOPERATION

VUOS key chemistry Adamantane derivatives N-Heterocycles API Building Blocks 10 VUOS ’s key technology Hydrogenation 10 VUOS – PARTNER FOR COOPERATION Phosgenation

VUOS technology/manufacture expertise includes: Organometallic and Cryogenic Chemistry • Organolithium Chemistry • Organozinc Chemistry • Grignards • Sodium Hydride Reactions Transition-Metal Catalysis • Homogeneous and Heterogeneous Transition-Metal Catalysis • Cross Couplings (Suzuki, Kumada, Heck, etc. ) 11 Hazardous and Unpleasant Chemistry • Phosgenation • Halogenation (PCl 3, POCl 3, SOCl 2, BCl 3, BBr 3, etc. ) • Rections with Nitroalkanes • Nitration • Sulfonation Reduction and High-Pressure Hydrogenations • Reduction with Sodium borohydride, Red-Al, Superhydride, etc. • Reductive Alkylation • Reductive Amination • Hydrogenolysis • Dehalogenation 11 VUOS – PARTNER FOR COOPERATION

Kilolab and Production Unit Phosgenation Reactors up to 1 600 l 2 x High performance rectification columns Laboratory phosgenation units from 1 to 30 l 12 VUOS – PARTNER FOR COOPERATION 12

Kilolab and Semi-Pilot Unit Hydrogenation 3 x autoclaves 100 l each, 60, 120 and 130 13 bar, up to 200 ˚C, Hastelloy C clad 1 x autoclave 300 l, 120 bar, 140˚C, Hastelloy C clad 1 x autoclave 700 l, 100 bar, 200 ˚C, stainless steel 1 x autoclave 1 000 l, 10 bar, 140 ˚C, stainless steel many small autoclaves up to 10 l 13 VUOS – PARTNER FOR COOPERATION

Kilolab and Production Unit Low temperature, RLi, RMg. X, Na. H Reactors up to 630 l cooled down to – 80 ˚C 1 x glass-lined reactor for Na. H reactions (250 l) 3 x glass reactors 100 l cooled down to – 40°C 14 VUOS – PARTNER FOR COOPERATION 14

Kilolab and Semi-Pilot Unit Multipurpose chemistry 15 20 x glass reactors, 100 l each 6 x glass lined reactors (200– 1 500 l) 2 x evaporators 50 l / h 4 x stainless steel reactors (300– 1 500 l) sufficient filtration and distillation capacity 15 VUOS – PARTNER FOR COOPERATION

GMP Production Line certified since 2015 Production of API Starting materials and advanced intermediates Controlled finalization of final products 16 Glass-lined vessels 400 and 630 l Stainless steel vessels 400 and 630 l Filtration, Centrifuging and Drying 16 VUOS - PARTNER FOR COOPERATION

Production Unit Production Equipment 17 52 x glass lined reactors, total vol. 85 000 l (500 – 6 000 l) 16 x stainless steel reactors, total vol. 29 000 l (1 000– 6 000 l) 8 x High performance rectification columns sufficient filtration capacity (nutsches, centrifuges) computer controlled 17 VUOS – PARTNER FOR COOPERATION

New Production Unit dedicated for production of Pharma Intermediates Purpose Dedicated for the production of pharma intermediates under the GMP standard 18 10 000 l volume of reactors (glass lined and stainless steel) Filtration, distillation, drying Supposed to be ready in the year 2017 Investment cost 4 mil. EUR 18 VUOS – PARTNER FOR COOPERATION

Toxicology, Ecotoxicology and Analytics 19 19 VUOS – PARTNER FOR COOPERATION

Toxicology, Ecotoxicology and Analytics REACH and CLP Services • Literature search • Preparation of dossiers in IUCLID 5 20 • Preparation of Chemical Safety Report • Non-testing approaches • (Q)SAR • Grouping/Read-across • • 20 Preparation of SDS Classification of substances and mixtures VUOS – PARTNER FOR COOPERATION

Toxicology, Ecotoxicology and Analytics Analytical methods • • Mass Spectrometry (LC/GC-MS) • ICP-AES • IR Spectrometry • Chromatography (HPLC, GC) • 21 NMR Spectrometry UV-VIS VUOS – PARTNER FOR COOPERATION 21

Toxicology, Ecotoxicology and Analytics Toxicological tests In vivo and in vitro tests according to the OECD or EU methods: • • Skin and Eye irritation • Sensibilisation • Repeated dose toxicity • Reproductive toxicity • Carcinogenicity • 22 Acute toxicity Mutagenicity VUOS – PARTNER FOR COOPERATION 22

Toxicology, Ecotoxicology and Analytics Ecotoxicological tests • Aquatic toxicity • Biotic degradation • Abiotic degradation • Adsorption/desorption Physico-chemical tests • Information on physicochemical properties of substance 23 VUOS – PARTNER FOR COOPERATION 23

Contacts General Manager: Dr. Karel Novák Phone: +420 46 682 2550, fax: +420 46 682 2976 e-mail: karel. novak@vuos. com Sales Manager: Miloš Jesenský, Ph. D. Phone: +420 46 682 3300, fax: +420 46 682 2976 e-mail: milos. jesensky@vuos. com R&D: Alois Koloničný, Ph. D. 24 Phone: +420 46 682 3156, fax: +420 46 682 3900 e-mail: alois. kolonicny@vuos. com Toxicology and Analytics: Michal Bartoš Phone: +420 46 682 2501, fax: +420 46 682 2975 e-mail: michal. bartos@vuos. com Process Engineering: Luboš Víšek Phone: +420 46 682 5790, fax: +420 46 682 3900 e-mail: lubos. visek@vuos. com 24 VUOS – PARTNER FOR COOPERATION

25 25 Výzkumný ústav organických syntéz a. s. Rybitví č. p. 296, 533 54 Rybitví, Czech Republic www. vuos. com