Vishwa-Syntharo PharmaChem Private Limited

December 2015

Background - Vishwa

• The name “Vishwa” originates from two Sanskrit words: Vishwas (Trust) & Vishwam (Global)

• Founded and whole-time managed by Dr. Sankara Subramanian with more than three decades of experience in leading pharmaceutical and chemical organizations in India

• Incorporated in March 2010 for providing chemistry and related services to the pharmaceutical and fine chemical industry

• Moved operations to Sri Ramachandra University, Chennai in October 2012 through a collaborative arrangement

• Collaboration forged with ProVentus Life Sciences, Chennai in December 2013 to have access to kilo and large-scale manufacturing

• Entered into a Joint Venture with Syntharo Fine Chemicals, Germany in September 2015.

Background - Syntharo

• Incorporated in April 1998 for the sale of fine & specialty chemicals

• Over the years, the company has developed into a manufacturer of intermediates , which are needed primarily for the synthesis of agrochemical & pharmaceutical ingredients (APIs ) and are used in cosmetic formulations

• 2005 – 2010, located at Leverkusen CHEMPARK

• In 2010, relocated to Industrial Park Troisdorf located between Cologne and Bonn , the former location of the Dynamit Nobel

• Involved in production of specialties on a laboratory scale

• Customers include catalogue companies, R & D departments of research-intensive chemical companies

• Other offices are located at:

Syntharo Fine Chemicals India Private Limited, Mumbai, India

USA – Syntharo Fine Chemicals USA Inc. New York, USA

Mission & Vision

Mission

Be a TRUSTWORTHY provider of products and services provider to the

Pharmaceutical and Speciality / Fine Chemical industry in all its fields of

operations

Vision

To be GLOBALLY renowned for excelling in Quality of Work, Integrity,

Innovation, Businesses processes, Technologies developed and Services

offered

Quality Policy

QUALITY POLICY

At Vishwa-Syntharo PharmaChem we shall continuously strive to provide our customers the best and timely delivery of products and services, through:

� Continuous improvements to our business processes;

� Developing and using the most appropriate technology that is efficient, cost effective and has least impact on environment;

� Maintaining a transparent and timely communication chain with the customer;

� Deploying appropriate human resources for the projects and continuously upgrading their skill and efficiency levels through periodic training and mentoring.

Dr R Sankara Subramanian

Education:

B.Sc – Vivekananda College, Chennai; M.Sc – Loyola College, Chennai

Ph.D – IIT Madras (Chennai); Post Doctoral – Univ. of Bath, UK

Previous work experience:

Recon Limited (now Hikal) -Establishment of Research Laboratories

-Process development for APIs

Shasun Chemicals & Drugs - Head of R&D

- Head of Corporate Quality Assurance & Regulatory

Affairs

- Strategic Business development

- Structure and commission CRAMS activities

Sanmar Speciality Chemicals

/ ProCitius Research

- Establish and lead the API division through FDA

inspection

-Establish and manage the Contract Research division –

ProCitius Research

ProVentus Life Sciences -Co-investor

-Restructure of business activities

- Establish and manage API and CRAMS business activities

Lars Müller

Background:

Founder and Director of Syntharo Fine Chemicals GmbH since 2008

Others:

CEO, Chem-Trade & Consulting GmbH, 1998 – 2007

Raimund Müller GmbH & Co. KG, 1993 - 2006

Research Advisor

Prof K K Balasubramanian

Education: PhD: University of Madras

Post Doctoral: Wayne State University, Detroit

(Amino- and keto- sugars with Prof Carl Stevens)

Background: Dept. of Chemistry, Indian Institute of Technology Madras

(1971 – 2001)

Industrial : Executive Director, R&D, Shasun Chemicals and Drugs (2001 – 2011)

Currently: Visiting faculty at Sri Ramachandra Univ. and Abdur Rahman Univ.

Expertise: Synthetic Organic Chemistry

Molecular rearrangements

Organic photochemistry & Electro-organic chemistry

Carbohydrate chemistry

Publications: 150

Students guided for PhD: 32

Key Awards: Lifetime achievement award CRSI Gold Medal 2012

Fellow of the Indian Academy of Sciences

Business Associate

Dr. K Vijayakumaran

Education:

M.Sc – University of Madras (Chennai);

PhD & Post Doctoral Research – University of Nancy (France)

Areas of Expertise:

Carbohydrate Chemistry - Synthesis of mono and polysaccharides

- Deuterated sugars

Oxidation reactions Chromium based reagents in organic oxidation of

complex organic molecules

Multi-step organic synthesis Several compounds synthesized for laboratory

chemical companies

Areas of Focus & Services

CustomManufacturing

(APIs, Fine &

Specialty chemicals)

ProcessDevelopment

(Fine / Specialty

Chemicals /

APIs)

Scale-upOf

Technologies

CustomSynthesis

(Fine / Specialty

Chemicals /

APIs)

AnalyticalServices

Chemistryfor

DrugDiscovery

Custom Synthesis:

� Develop process

� Scale-up to make required quantity of chemical (grams to multiple of kilos)

Process Development:

� Development of processes for hard-to get molecules

� Scale-up and supply can be made in-house or technology can be licensed to

second- or third-party

Chemistry for Drug Discovery:

� Synthesis of customized libraries

� Synthesis of targets

� Lead optimization (with provided inputs)

Analytical services:

� Analytical method development

� Synthesis and characterization of hard-to-get impurity standards

Scale up of Technologies:

� In-licensing of laboratory scale processes, fine-tuning them and scaling up to

make larger quantities as required

Key Chemistry Capabilities

Asymmetric

Synthesis

� Chiral alkylation

� Asymmetric Dihydroxylation,

� Sharpless, Heck Epoxidation

Oxidation � Classical (Jones, KMnO4, CrO3, MnO2 etc)

� Swern

� Moffat

� Corey-Kim

� Transition Metal Catalyzed

Reduction � Metal Hydrides

� Homogeneous & Heterogeneous catalysed

� Transfer Hydrogenation

� Dissolving Metal Reduction

Others � Fluorination (NFSI, DAST, selectfluor, deoxo-fluor)

� Carbonylation

� Cyanation

Organometallic � Heck arylation

� Suzuki coupling

� Sonagashira coupling

Chemistries that we do not handle: Reactions involving Phosgene; HCN gas

Common chemistries regularly performed is not included in above.

Carbohydrate Chemistry

Basic monosachharidesDifferentially protected and derivatized monosaccharides

PolysaccharidesTypically di- and tri- saccharides

Protected amino-sugars

Such as (D)-Glucosamine

Configurational inversion

Such as SN2-displacement or oxidation-reduction sequence) to arrive at rare

sugars

Carbohydrate-derived chiral synthons

Performing sequential chemical transformations on the chiral-pool derived from

sugars to make chiral synthons

O

H

AcO

OAc

H

H

Br

OAcHH

OBn O

H

H

HO

H

OH

OHHH

OH

O

H

HO

H

HO

H

O

OHHH

OH

OH

H

H

H OH

HO H

O

H

HOHO

Fluorine Chemistry

Fluorinated chemicals

Custom synthesis of:

• Fluorinated starting materials

• Fluorinated intermediates

• Fluorinated drugs

Typical fluorinating agents used:

• NFSI;

• DAST (at small scale only);

• Selectfluor; deoxo-fluor

S S

N

F

O

O

O

O

N

SF3

CH3 CH3

H3CO

N

OCH3

SF3N

N

Cl

F

2 BF4

COOHF

O

FFF

CF3

F

Chiral chemistry

� Resolution of compounds by chemical method

� Asymmetric / enantioselective synthesis

� Steroselective synthesis using enzymes

Chiral purity estimated by:

� Chiral HPLC

� Optical rotation

� NMR using chiral shift reagents

Research & Development

Fume Hoods: 5 (in Phase 1)

Rotary evaporator Buchi 4 nos.

Scale: 5 ml to 10 litres

Temperature range: - 70 to + 250 deg C

Vacuum: Double-stage water-ring vacuum: 60 mm 1

Diaphragm pump: 10 mm 2

Oil vacuum pump: 0.1 mm 4

High pressure 250 ml SS 316 shaker Temp: Ambient to +250 C

Pr.: Ambient to 30 Kg

2

5 lit Temp: Ambient to +250 C

Pr.: Ambient to 30 Kg

1

10 lit SS 316 *

Capabilities: � Column chromatographic purification

� Fractional distillation

� Cryogenic reactions

� Organo-metallic reactions

* - Under procurement

Analytical

GC: Under procurement

GC-HSS: Under procurement

GC-MS: Perkin Elmer Claruss 600 GC with 600 C MS(Outsourced from Ramachandra Univ. / VClinBio; turn-around time 12 - 36 hrs)

HPLC: Shimadzu LC-2010

Shimadzu LC-2010A HT

Shimadzu LC-8A

NMR: Bruker 400 MHz (Outsourced from Ramachandra Univ. / VClinBio; turn-around time 12 - 36 hrs)

HPTLC: CAMAG-ATS-4(Outsourced from Ramachandra Univ. / VClinBio; turn-around time 12 - 36 hrs)

LC-MS: Agilent

FT-IR: Under procurement

UV-Vis: Under procurement

Auto-titrator: Under procurement

Kilo-lab 1

Low-level fume hoods for 20 liter flasks 2

100 Lit all glass unit 2

20 Lit fractional distillation 1

20 Lit Rotary evaporator 1

Vacuum tray dryer (4 trays / 5 to 10 kgs) 1

Nutsche filter (PP) 1

Air quality:Air conditioned Clean area (Not classified)

Operation conditions:Temperature: -70 to + 250 deg CVacuum: 1 mm HgPressure: Ambient

Kilo-lab 2

250 Lit reactor (SS 316) 1

250 Lit reactor (MS-GL) 1

Centrifuge (SS 316) (36”) 1

Nutsche filter (PP) 1

Vacuum tray dryer (6 trays / 10 to 25 kgs) 1

Multi-mill 1

Sieve shaker 1

Operation conditions:Temperature: -15 to + 150 deg CVacuum: 1 mm HgPressure: Ambient

Air quality:Filtered airClass 100,000

Key Achievements of Vishwa-Syntharo

Target No of

steps

Other

Manufacturers

Status Customer

Fine chemical

for New API

2 Limited API just approved

Under commercial prodn.

MNC Pharma

Intermediate

for API

2 Limited Production to start MNC Pharma

CONTACT

Registered Office:

32, First Main Road

CIT Colony,

Mylapore,

Chennai – 600004

Tamil Nadu, India

info@vishwa-syntharo.com www.vishwa-syntharo.com

R&D:

2C Dr. Subramania Siva Salai

CMDA Industrial Estate

Maraimalai Nagar

Chennai 603 209

India

Vishwa-Syntharo PharmaChem Private Limited

Tel: +91 44 43536710

Germany:

Syntharo Fine Chemicals GmbH

Industriepark Troisdorf Geb. 38

Mülheimer Strasse 27

53840

Troisdorf, Germany

Tel: +49 2241 25569-0Tel: +91 44 47431610