civentichem india presentation for clients - jan 2011

Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters

Venugopal Rao Veeramaneni, Ph.D.

Head R&D and Manager Project Management

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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters2

Our VISION is to provide an integrated chemistry services platform to help our Clients to IMPROVE the success of research, shorten the time of development, and REDUCE RISK by offering our customers a reliable, efficient and high quality environment in which to DELIVER projects.


• Core Competencies• Key Services• History• Business Overview• Global Advantage• Services and Capabilities• Management Experience and Chemistry Expertise• Facilities• Case Studies

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Highlights of Presentation


Core Competencies

• Complex Organic Chemistry

• Milligrams to Multi Kilogram Scale Synthesis

• Process Development & Optimization

• Diverse Manufacturing Skills

• Project Delivery & Democratization of Science

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Key Services

• Contract Research & Medicinal Chemistry

• Custom Synthesis at Milligrams to Multi Kilograms

• Process Development & Route Optimization

• Pilot Plant Scale-up

• Contract Manufacturing

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History

• 1994 - Founded in RTP, North Carolina• 1999 – Expanded to Larger Laboratory• 2000 – Reached 12 Scientists• 2002 – R&D Laboratories Opened in India• 2005 - Moved to Current Facility in Cary• 2008 - Analytical Services Began in Cary• 2009 – Launch of Pilot Plant in India• 2010 - 1st Project in Pilot Plant in Hyderabad• 2011 - Start cGMP Kilo-Lab Synthesis in RTP

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Business Overview• HQ: RTP, North Carolina• Services: Chemistry

– Discovery & Synthetic Chemistry, Process Development, Manufacturing & Analytical Services

• People: 80 Total– 75 Experienced Scientists plus Administration

• Facilities: USA and India– RTP, North Carolina and Hyderabad, India– 50,000 Sq Ft Total Technical Facilities

• Customers: Around 150– including 10 of world Top 20 Pharma; 45 Biotechnology

Companies.

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Biological

TargetScreening Hits LaunchClinicalLeads

Drug

candidate

Pre -

clinical

ScreeningCompounds

CustomSynthesis

ParallelSynthesis

MedicinalChemistry

ManufacturingPilotPlant

ProcessScale-up

Associated

Chemistry

Peakdale Molecular Collaborators

-

Biological

TargetScreening Hits LaunchClinicalLeads

Drug

candidate

Pre -

clinical

ScreeningCompounds

CustomSynthesis

ParallelSynthesis

MedicinalChemistry

ManufacturingPilotPlant

ProcessScale-up

Associated

Chemistry

CiVentiChem USA & India CiVentiChem India

-

Integration in the Pipeline

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DEVELOPMENT CHEMISTRY•Rapid Initial Scale-up to first Kg•Process Research & Development•Feasibility Studies•Pilot Development Manufacture•Manufacture Intermediatess & APIs•cGMP & Non-GMP Protocols

RESEARCH CHEMISTRY •Medicinal Chemistry•Focused Libraries•Reference Standards & Metabolites•Lead Compounds & NCEs•Lead Optimization•Intermediates and Building Blocks available and in-stock

PRODUCTION CHEMISTRY •Pilot Development Manufacture•Process Research & Development•Contract Manufacturing •Manufacture Intermediates &

APIs


Existing Clients

Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters11

Global operations in the USA and India with project management, IP control and local solutions at our USA headquarters.


Global Advantages

Flexibility of Choice… USA or India or BOTH !!• Project Type• Deadline• Output Scale or Volume• Research Requirements• Expertise Requirements• Communication and Project Control• Lowest Cost

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Global Advantages

Process Scaled-Up for the Lowest Costs• CiVentiChem USA Responsible for:

– Confidentiality Agreements– Project Oversight– Communication & Control with Client– Supply Chain Management

• CiVentiChem INDIA Responsible for:– Chemistry Implementation– Meeting Delivery & Quality Targets– Lowest Cost of Large Scale Production

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Services and Capabilities

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Chemistry Services

• Medicinal Chemistry• Synthesis of Focused Libraries & Analogues• Synthesis of Reference Standards &

Metabolites• Synthesis of Lead Compounds & NCEs• Lead Optimization & Parallel Synthesis• Novel Template Molecules Ready for Purchase

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Development Services

• Rapid Initial Scale-up to 1st Kilogram• Process Research• Process Development & Optimization• Feasibility Studies• Pilot Developmental Manufacture• Contract Manufacturing • Manufacture of Intermediates & APIs• cGMP & Non-GMP Protocols

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Chemistry Expertise and Management Experience

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Management ExperienceDr. Bhaskar R. Venepalli - President and CEO• 13 yrs Eastman R&D, New Product & Business Mgmt• Expertise in CRAMS, Advanced Life Sciences & Fine Chemicals Dr. Srinivas (Vasu) Chittineni - CTO• Co-founder of CiVentiChem in 1994• Expertise in Complex Organic Syntheses, Chiral & Carbohydrate ChemistryDr. S. Venkataiah - Managing Director• Pharmaceutical & Flavor Industrial Expertise• Director of R&D (20+ years) at Aurobindo Pharmaceutical in India• Developed processes for 22 bulk drugs & Transferred to Mfg PlantsDr. Venugopal Veeramaneni – Head R&D and Project Management • Drug Discovery and Medicinal Chemistry Expertise• Reddy Labs Sr. Research Scientist in Therapeutic Areas Of Oncology, Metabolic Disorders

and CNS

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Research Team at CiVentiChem India 1. Dr. Hari Chitineni,

Section Head, Process DevelopmentExperience in Carbohydrate, Heterocyclic Chemistry and Process Development

2. Dr. C.V. Laxman Rao,

Section Head, Medicinal Chemistry Experience in in Asymmetric and Multi-step Synthesis in Med Chem

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• Sugar Molecules • Chiral Catalysts and Reagents • Reagents for peptide formation• Novel Hetero cyclic compounds for supporting all the stages in

drug discovery.• Pyrazoles, Isoxazole, Oxazoles, Pyrazines, Pyridazines,

Pyrimidines, Pyrrolopyrimidine, Azaindoles, Indazoles, Piperidinopyrimidines and Heterocycles having Spiro group

• Chiral Binaphthols & Boronic Acids• Reference Standards for Med Chem/Biology Support • Novel Building Blocks for Drug Discovery/Med. Chem.

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Chemistry Specialties


• All General Reactions - mg to Kg scale• Temperature range: -78 oC to + 200oC (small scale)• Temperature range: -5 oC to + 140oC (large Scale)• Grignard Reactions – Up to 50 kg of Mg charge• Cyanation Reaction – mg to multi Kg scale• Bromination – mg to multi Kg scale• Hydrogenation Reactions – 350L SS, 30 kg/cm²• Transition Metal Reactions & Enzymatic Resolutions • Reactions in Aqueous medium • Phosgenations using triphosgene

Chemistry Capabilities


Chemistry Experience Range of products Available

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Azaindoles & (1H)-Indazoles

N NH

X = I

X

N NH

X

N NH

4,5,6,7-Azaindoles and Mono/DiSubstituted 7-Azaindole:

X = Cl, Br, I, CN & CHO

X = Cl, Br & OH

NH

N

4,5,6Azaindoles

N NH

YX

X

N NH

XY

X=Cl, Y=Cl, Br, I, CN. CHOX=Br, Y=Cl, I, CN, CHO

X=Br, Y=Cl, Br, I, CN. CHO

Substituted IH-Indazoles:

X=Br, CHO, CO2Me, CO2H, CH2NH2X = Br

NH

NNH

NNH

N

X X

X

NH

N

X

X= H, Cl, I, Br, CN & CO2H

NH

NX

Y

X=Br, CHO, CO2Me, Y=Cl, I


Pyrimidines

Aryl β-Keto & Diketo esters

O O

Y

O O

OEt

R=Cl, Br, F, I, Me, OMe, CF3, Y=OEt, CO2Et

R NH

O O

OEt

N

O O

OEt

O

O O

OEt

Aryl Beta Keto & Diketo Esters

R= Cl, Br, F, OMe, Me;

N

N

Cl

NH

RN

N

R

O

O

R1

N

N

R

O

O

R1

N

N

R

OO

R= Cl, Br, F, OMe, Me;R1=H, Me & Et

R= AlkylsR1=H, Me & Et


Pyrazole Derivatives

Isoxazole Derivatves

N NH

O

O

R1

X

N NH

O

O

R1

X R

N NH

R

O

O

R1N N

H

X OO

R1

N NH

X OO

R1

R N NH

RO

OR1

X= Cl, Br, F, OMe, Me; R=H & Me, Et, Pr, iPrR1=H, Me & Et

X= Cl, Br, F, OMe, Me; R=H & Me, Et, Pr, iPrR1=H, Me & Et

R=H & Me, Et, Pr, iPr, CyPrR1=H, Me & Et

ON

R

O

O

R1

R= Cl, Br, F, OMe, Me; R1=H, Me & Et

NO

R= Alkyls & Substituted Aryls R1=H, Me

NO

R

R= Cl, Br, F, OMe, Me; R1=H, Me

H2N

R1

R

O

O

R1


2-Naphthol Derivatives (R & S Isomers)

Reagents & Catalysts

OH

OH

OMOM

OMOMOTs

OTsOAc

OAcOH

OH

Br

Br

NH

OH

R

R

R

RR-DPP & S-DPPR & S IsomersR=H & CF3

NH

O

R

R

R

RR & S IsomersR=H & CF3

Si N

O

O

O O

O

N

O

O

DSC

N

Co

N

N

N

O O

H

O OH

Py

Cobaloxime

N N

N

HNNH

O

O


Drug Intermediates in Bulk

N NH

XCl

NH

N

X

N NH

CO2H

NH

NH2

HCl

NH

N

RO2C

R = H, Me

NH

N

R = H, Me

RO2C

NCl Cl

O

N NH

X

NH

N

Br

N NH

X

N NH

BrX

X = Cl, I

OH

Br

O O

SO

O

NH2N

HNNH2

Ph

X = Cl, Br, IX = H, Br, I X = Cl, Br, I

X = Cl, Br

NH

N

Br


Chemistry Experience

OVERALL

• Over 100,000 Chemical Stages

• Over 300 Years of Technical Experience

• Over 100 Years of Management Experience

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Facilities

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Facilities - USA

Research Triangle Park, NC

• Modern Laboratory• Capacity to Work from Milliliters to 50 Liters• High Pressure/Temperature Equipment• World Class Analytical Equipment (NMR, HPLC,

LC-MS, etc,.)• Access to Exceptional Talent (UNC, Duke & NC

State)• cGLP Analytical Lab

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Facilities - USA

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Facilities - India

Hyderabad, India

• 12,000 Sq Ft Laboratory • Vicinity of IICT & Osmania University• Analytical Capabilities (HPLC, GC, LC-MS)• Provide Lowest-Cost Large-Scale Production • Supply Chemists, Capabilities & Products• Access to Modern Library & Exceptional

Scientific Talent from National Labs

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Facilities - India

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Facilities - India

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Facilities - India

Pilot Plant – General • 22 Reactors - Total Capacity of 15,000 L• Perform Reactions from -100 oC to +120 oC• High Vacuum Distillation• Extensive Auxiliary Filtration, Drying, Milling• Dedicated Clean Room Facilities for All Areas• Process R&D and Large-Scale Manufacturing• Separate Isolated cGMP Suites - 3• Separate QC Laboratory and Documentation Center

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Facilities - India

Pilot Plant - Equipment Configuration• Stainless Steel Reactors:

– 2500 L(1); 1600 L(2); 1000 L(1); – 500 L(2); 350 L(4) & 250 L (4)

• GLMS Reactors: – 2000 L(1); 1000 L(2); 630 L(1) &250 L(1)

• Autoclave (Hydrogenation): – 350 L(1); 50 L(2); 5 L(1) and 2.5 L(1)

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Manufacturing EquipmentSS316 Reactor 1200L 2 No'sSS316 Reactor 1000L 1 NoGlass Lined Reactor 1000L 1 NoSS316 Reactor 250L 2 No'sSS316 Reactor 350L 2 No'sSS316 Reactor 2000L 1 NoSS316 Reactor 500L 1 NoGlass Lined Reactor 160L 2 No'sGlass Lined Reactor 250L 1 NoGlass Lined Reactor 500L 1 NoGlass Lined Reactor 1600L 1 NoCentrifuze SS316 36“ 1 NoCentrifuze SS316 24" 1 NoCentrifuze SS316 18" 1 NoRotocone GL dryer 250 L 1 NoRotocone SS316 dryer 50 L 1 NoTray dryer 12 trays 1 NoVacuum Tray dryer 6 Tray 1 NoTray dryer 24Tray 1 NoSifter 24“ 1 NoMulti mill 25 Kg/Hr 1 NoSifter 12“ 2 No'sMulti mill 10 Kg/Hr 2 No'sCooling tower 70 TR 1 NoCooling tower 30 TR 1NoVacuum Pumps 300M3/Hr 4 No‘s

R&D , Stores and QCR&D Labs:Fume Hoods 27 No’s Cooling Tower 30TR 2 No’s Vacuum Pumps 120M3/Hr 4 No’s Analytical Equipment: HPLC (Quartanery & Gradient) 2 Nos Preparative HPLC, LCMS & GC - 1 No Each

Production Block

Utility Block Diesel Generator 180 KVA 1 NoOil Fired Boiler 1 Ton/Hr 1 NoN2 Generator 99.5 %, 5 m3/h 1 NoDM Plant (with RO) 40 m3/Reg 1 NoAir Compressor 70 CFM 1 No

Corrosive Block FRP Reactor 2000L 1 No Glass Lined Reactor 1600 L 1 NoGlass Lined Reactor 630L 1 NoGlass Lined Reactor 100L 1 NoHydrogenator -SS316 -350L (25 Kg) 1 NoBrine Compressor (-20 DEG) 15 TR 1 NoCooling tower 165 TR 1 NoCentrifuze SS316 & halar coat 36“ 1 No


Analytical Facilities CiVentiChem, India

S. No. Name of the Instrument No. of instruments

Make

1 High Performance Liquid Chromatograph With PDA detector

2 Agilent

2 High Performance Liquid Chromatograph With VWD detector

1 Agilent

3 High Performance Liquid Chromatograph(RRLC) with PDA

Detector

1 Agilent

4 Preparative HPLC 1 Agilent5 Gas Chromatograph with FID Detector 2 Agilent6 Liquid Chromatograph-Mass

Spectrometer(LCMS)11

AgilentSchimadzu


S.No. Name of the Instrument No. of instruments

Make

7 Analytical Balance 2 Denver, Sartorius

8 Ultrasonicator 2 PCi

9 Digital PH-Meter 2 POLOMON & GLOBAL

10 Microprocessor PH-Meter 1 GLOBAL

11 Conductivity & TDS Meter 1 GLOBAL

12 Melting Range Apparatus 2 POLOMON

13 Karl Fischer Apparatus 2 POLOMON

14 Milli-Q Water purification system 2 Millipore

Analytical Facilities CiVentiChem, India


Case Studies

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Case Study #1

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Lead Optinization and Medicinal Chemistry:FORTUNE 100, Vice President of Research

PROBLEM: Many molecules needed for screening to optimize lead molecules. Required experienced synthetic chemists but had very tight timelines.

SOLUTION:Discovery supportMade several hundred analogs for lead optimization50-100 mg of each and purification by column chromatographywith our chemists on FTE basisContinuous communication & collaboration throughout


Case Study #2

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Lead Optimization Through to Pre-Clinical DevelopmentStart-up Biotech Company, CEO and CSO

PROBLEM: Needed to move quickly from lead molecule to ther clinic, timeframe was short since previous contractor failed to deliver.

SOLUTION:Made Several APIs on 100 g scale in our US laboratoriesTen-step synthesis & complex chemistry, including resolution & asymmetric synthesesScaled-up and produced large volume of key Intermediates Transferred the process to IndiaProduced product in India at significantly lower cost


Case Study #3

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Reference Standards and IntermediatesMid-size Pharma, Director of Process Chemistry

PROBLEM: In-house resources were backlogged; testing faces major delay.

SOLUTION:Synthesized reference standards (chiral heterocycle) Made 10 g of 14-step synthesis product with chiral induction & cyclization to a 7-membered heterocyclic ringMade 10 chiral carbohydrates involving 8-10 stepsSeveral heterocyclic building blocksHandled sensitive reagents and manipulated protecting groups.


Case Study #4

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Pre-Clinical Development:BIG PHARMA, VP of Chemistry, Director of Med-Chem.

PROBLEM: No scale-up capabilities for the lead molecule. Chemistry involved sensitive reagents on a large scale.

SOLUTION:Made 500 g of API via a 9 step synthesis Dianion chemistry involving n-BuLi & t-BuLi, -78 oCDiels-Alder reaction, Michael additionHigh pressure hydrogenationLarge-scale handing of sensitive reagentsCompound is now in Phase II


Case Study #5

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Guidance, Consultancy and Intellectual InputVirtual Pharma Start-Up, CEO

PROBLEM: Had no in-house resources or chemistry technical expertise, needed consultancy and technical support. Throughout.

SOLUTION:Initial consultancy and on-site discussionLed to novel ideas & new synthetic schemesNovel building blocks synthesizedNew method development for pharma intermediatesRefined synthesis from 9 steps to 6 stepsNew products & technologies


Case Study #6

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Large Scale Development and ManufacturingMid-Size Pharma, Director of Manufacturing

PROBLEM: Internal and external production delay was imminent and so needed a large quantity of a key intermediate quickly.

SOLUTION:Large Scale (300 kg) synthesis of a heterocyclic compound Refined synthesis to 5 stepsProduced in India & avoided production delaysInvolved C-alkylation, anion chemistry, halogenation & acetylation


For inquiries, please contact:

Dr. Venugopal Rao VeeramaneniCiVentiChem India Limited[Formerly known as Indus BioSciences (P) Ltd.,]Plot No. 72/A, Part 2, Phase-I, I.D.A., Jeedimetla,Hyderabad, A.P. , India..

Tel : +91-40-23197766/67/68 Ext: 228; Fax : +91-40-23091692Mobile: +91-9030026010; e-mail : [email protected] www.civentichem.com

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THANK YOUVenu

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civentichem india presentation for clients - jan 2011

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