DSM Innosyn TM. Innovative Process Research Services For Localization of API Manufacturing and Advanced Intermediates. DSM Chemical Technology BV

Transcription

1 DSM Innosyn TM Innovative Process Research Services For Localization of API Manufacturing and Advanced Intermediates DSM Chemical Technology BV André de Vries April

2 Mission of DSM Our purpose is to create brighter lives for people today and generations to come. We connect our unique competences in Life Sciences and Materials Sciences to create solutions that nourish, protect and improve performance. Page 1

3 Global presence World total ~23,500 employees North America: ~5,000 employees China: ~3,500 employees Europe: ~13,000 employees India: ~500 employees Latin America: * ~1,000 employees Page 2

4 Global societal trends drive DSM s markets Health & Wellness Global shifts Climate & Energy Aging population Healthcare costs Population growth Urbanization Resources constraints Energy security Food security Wealth Sustainability Health Nutrition Materials Page 3

5 Key strengths in Pharma Anti-infectives Custom Manufacturing Biologics Market leader in β-lactam APIs Strong presence in high efficacy statins Technology leader Global reach, strong in Asia Global production footprint Well recognized highquality supplier to leading pharma houses Excellent regulatory track record Outstanding R&D and manufacturing competencies Most cost-effective manufacturing technology (XD, Rhobust ) Lowest investment plant concept DSM biotech heritage Page 5

6 Example: Anti-infectives Long history in sustainable production of antibiotics Fermentation & metabolic engineering Chemistry & Biocatalysis Biocatalytic coupling Page 6

7 Statins - Common intermediate Proprietary, enzymatically produced intermediate: Independent of intermediates used by industry High yields and efficient side chain coupling lead to unrivalled purity and low carbon footprint. Compliant with the strictest (draft) monographs

8 Rosuvastatin New process Page 9

9 DSP s Rosuvastatin Unique Technology Breakthrough Backward integration ECO+ Regulatory DSP process Efficient route of synthesis with FTO upon compound patent expiry. Process protected by nine (9) patent (applications) 5-6 steps Proprietary enzymatic process Highly efficient FTO process with ultraefficient side-chain coupling and amine Plan for full backward integrated technology, including side-chain Aim for lower carbon footprint compared to competition Use of 2 nd generation Bio-fuels Compliance to DRAFT EU monograph and relevant/applicable guidelines Competition Non-differentiating routes using expensive Wittig or Wittig-Horner process >8 steps Extra enzymes and/or chemical steps required to compensate DSP enzymatic process Sourcing key intermediates and sidechains from dominant Chinese player(s) Full control via in-house manufacturing in second half of 2014 and alternative DSP controlled partner sites For products of DSM Sinochem Pharmaceuticals please contact: evelina.smagina@dsm-sinochem.com

10 DSM Custom Manufacturing (CM) of small molecule API Custom Manufacturing Well recognized highquality supplier to leading pharma houses Excellent regulatory track record Outstanding R&D and manufacturing competencies Page 11

11 11 th of March 2014: Royal DSM and JLL Partners create DPx DSM s new CM landscape for small molecule API Desk Studies Route Scouting Preclinical & Early clinical Clinical development/ validation (phase 2+3) Registration & Launch DPx DSM Innosyn TM CRO ResCom DSM Fine Chemicals DFC Linz & Venlo

12 DSM InnoSyn TM - Route Scouting Services Focus: All Pharma Houses (worldwide); Agro Chemicals; Fine chemicals Consulting Ideation for synthesis routes for your API Route scouting Identification of the (best) alternative routes (Bio)catalyst screening Identification of the most promising catalysts Pre-feasibility Proof-of-principle based on parameter optimization (incl. micro-reactor technology) Full feasibility Tech package, sample preparation and licensing options Mini-plant services Page Kg supply, 13 support in transfer and implementation

13 DSM InnoSyn TM - Route Scouting Services Russia All process research capabilities available for localization of API manufacturing, or of advanced intermediates Key features are: - Low cost routes - Biocatalysis & Homogeneous Catalysis - Process Intensification (flow reactors) - Sustainability - Freedom to Operate - New IP possibilities, new IP for the customer - Tech transfer support, if appropriate - FTE hire, or on project base (modular approach) Page 14

14 Example: Process Intensification Case study: (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol (hexafur) Process developed at DSM based on multi-step synthesis starting from L-ascorbic acid Hexafur is one of the key building blocks of Darunavir, a 2 nd generation protease inhibitor (anti-hiv) Page 15

15 DSM process EP ; Org.lett. 2005, 7, 5917 Safety issues in Michael addition and Nef reaction 1. Exotherm during dosage of DBU 2. Chance of precipitation of Na-salt of nitro methane Flow reactor Page 16

16 Flow reactor set up DBU feed T-mixer Productivity: 12 g lactone/hour V reactor =3,70 ml Φ inw = 0.35mm Substrate/nitromethane feed Page 17

17 Process Intensification Now Michael addition (MA) in flow reactor (higher conc.) Neutralization with aq NaOH Continuous extraction Crystallization under epimerizing conditions (DKR) Impact Improved safety Less solvent recycle Increased yield (~10%) Increased productivity Batch process MA Nef Neutr. HCO3 distill MeOH extraction Solvent switch cryst. Semi-continuous process MA Nef Neutr aq. NaOH distill MeOH extraction distill solvent cryst. (DKR) Batch Contineous Page 18

18 Interested in route scouting and process research services for localization of API manufacturing? Please contact us: DSM Innosyn TM Page 19

19 Safe harbor statement This presentation may contain forward-looking statements with respect to DSM s future (financial) performance and position. Such statements are based on current expectations, estimates and projections of DSM and information currently available to the company. DSM cautions readers that such statements involve certain risks and uncertainties that are difficult to predict and therefore it should be understood that many factors can cause the company s actual performance and position to differ materially from these statements. DSM has no obligation to update the statements contained in this presentation, unless required by law. The English language version of this document is leading. A more comprehensive discussion of the risk factors affecting DSM s business can be found in the company s latest Annual Report, which can be found on the company's corporate website, Page 20