Venugopal Rao Veeramaneni, Ph.D.

Head R&D and Manager Project Management

Global operations in the USA and India with project management,

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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.
Global operations in the USA and India with project management,
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 Highlights of Presentation
• Core Competencies
• Key Services
• History
• Business Overview
• Global Advantage
• Services and Capabilities
• Management Experience and Chemistry Expertise
• Facilities
• Case Studies

Global operations in the USA and India with project management,

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 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
Global operations in the USA and India with project management,
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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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 Integration in the Pipeline
Biological Screening Drug Pre -
Screening Hits Leads Clinical
Clinical Launch
Target candidate
candidate clinical

Associated Screening Parallel Medicinal Custom Process Pilot

Manufacturing
Chemistry Compounds Synthesis Chemistry Synthesis Scale -up Plant

CiVentiChem USA & India

Peakdale Molecular CiVentiChem India
Collaborators

RESEARCH CHEMISTRY DEVELOPMENT CHEMISTRY PRODUCTION CHEMISTRY

•Medicinal Chemistry •Rapid Initial Scale-up to first Kg •Pilot Development
•Focused Libraries •Process Research & Manufacture
•Reference Standards & Development •Process Research &
Metabolites •Feasibility Studies Development
•Lead Compounds & NCEs •Pilot Development Manufacture •Contract Manufacturing
•Lead Optimization •Manufacture Intermediatess & •Manufacture Intermediates
- &

•Intermediates and Building APIs APIs

Blocks available and in-stock •cGMP & Non-GMP Protocols
Global operations in the USA and India with project management,
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Existing Clients

Global operations in the USA and India with project management,

IP control and local solutions at our USA headquarters
Existing Clients

Global operations in the USA and India with project management,

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

Global operations in the USA and India with project management,

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

Global operations in the USA and India with project management,

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IP control and local solutions at our USA headquarters
 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

Global operations in the USA and India with project management,

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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
Global operations in the USA and India with project management,
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Chemistry Expertise and
Management Experience

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 Management Experience
Dr. 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 Chemistry
Dr. 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 Plants
Dr. 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 Development
Experience 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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 Chemistry Specialties
• 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.

Global operations in the USA and India with project management,

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 Chemistry Capabilities
• 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

Global operations in the USA and India with project management,

IP control and local solutions at our USA headquarters
 Chemistry Experience
Range of products Available

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Azaindoles & (1H)-Indazoles
4,5,6,7-Azaindoles and Mono/DiSubstituted 7-Azaindole:
X X Y Y
X
N X X
N N N N N N N N N
H H H H N N
H H
4,5,6 X=I X = Cl, Br, I, X = Cl, Br & OH X=Cl, Y=Cl, Br, I, CN. CHO X=Br, Y=Cl, Br, I,
Azaindoles CN & CHO X=Br, Y=Cl, I, CN, CHO CN. CHO

Substituted IH-Indazoles:
X X Y
X
N N N N X N
N N N X N N
H H H H H
X = Br X=Br, CHO, CO2Me, CO2H, CH2NH2 X=Br, CHO, CO2Me, Y=Cl, I
X= H, Cl, I, Br, CN & CO2H

Global operations in the USA and India with project management,

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 Aryl β-Keto & Diketo esters
Aryl Beta Keto & Diketo Esters O O O O
O O
O O O O
OEt OEt OEt
Y OEt
O
R N N
H
R=Cl, Br, F, I, Me, OMe, CF3, Y=OEt, CO2Et

Pyrimidines
Cl O O O
O
R1
N O N R1
R O N N
N N N
H R R N R N
R= Cl, Br, F, OMe, Me; R= Alkyls
R= Cl, Br, F, OMe, Me; R1=H, Me & Et
R1=H, Me & Et

Global operations in the USA and India with project management,

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 Pyrazole Derivatives
R1 R1
O R1 O
X O O
X X R X O O
R O R
O O
N N N N R N N
N N O R1 N N O R1 N N
O R1 H H H
H H H
X= Cl, Br, F, OMe, Me; X= Cl, Br, F, OMe, Me;
R=H & Me, Et, Pr, iPr R=H & Me, Et, Pr, iPr, CyPr
R=H & Me, Et, Pr, iPr R1=H, Me & Et
R1=H, Me & Et R1=H, Me & Et

Isoxazole Derivatves
R H2N
N O O R1 O O
N N
O O
R R1 R R1
O
R= Cl, Br, F, OMe, Me; R= Alkyls & Substituted Aryls
R1=H, Me R= Cl, Br, F, OMe, Me;
R1=H, Me & Et R1=H, Me

Global operations in the USA and India with project management,

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2-Naphthol Derivatives
(R & S Isomers)
Br

OH OMOM OTs OAc OH

OH OMOM OTs OAc OH

Br

R
Reagents & Catalysts
R
H
R R O O
O O N
O O N N
OH O Si N N N N O
N N Co
O O
H R H O O N Py N N
R
HN H
DSC O O
R R H
R-DPP & S-DPP R & S Isomers
R & S Isomers R=H & CF3 Cobaloxime
R=H & CF3
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 Drug Intermediates in Bulk
Cl X X X
CO2H
X Br

NN N N N N N N
H N H H N
H H
X = H, Br, I X = Cl, Br, I X = Cl, Br, I X = Cl, I

X
Br RO2C
N N N N N
N Br N N N N
H H RO2C H
H H
X = Cl, Br R = H, Me R = H, Me

O NH2 OH
HN O
S
O NH2
Cl N Cl N
N NH2 O O H HCl

Ph Br

Global operations in the USA and India with project management,

IP control and local solutions at our USA headquarters
 Chemistry Experience

OVERALL
• Over 100,000 Chemical Stages

• Over 300 Years of Technical Experience

• Over 100 Years of Management Experience

Global operations in the USA and India with project management,

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Facilities

Global operations in the USA and India with project management,

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

Global operations in the USA and India with project management,

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IP control and local solutions at our USA headquarters
Facilities - India

Global operations in the USA and India with project management,

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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 Equipment
Production Block R&D , Stores and QC
SS316 Reactor 1200L 2 No's R&D Labs:
SS316 Reactor 1000L 1 No Fume Hoods 27 No’s
Glass Lined Reactor 1000L 1 No Cooling Tower 30TR 2 No’s
SS316 Reactor 250L 2 No's Vacuum Pumps 120M3/Hr 4 No’s
SS316 Reactor 350L 2 No's
SS316 Reactor 2000L 1 No Analytical Equipment:
SS316 Reactor 500L 1 No HPLC (Quartanery & Gradient) 2 Nos
Glass Lined Reactor 160L 2 No's Preparative HPLC, LCMS & GC - 1 No Each
Glass Lined Reactor 250L 1 No
Glass Lined Reactor 500L 1 No Utility Block
Glass Lined Reactor 1600L 1 No
Centrifuze SS316 36“ 1 No Diesel Generator 180 KVA 1 No
Centrifuze SS316 24" 1 No Oil Fired Boiler 1 Ton/Hr 1 No
Centrifuze SS316 18" 1 No N2 Generator 99.5 %, 5 m /h 3
1 No
Rotocone GL dryer 250 L 1 No DM Plant (with RO) 40 m /Reg3
1 No
Rotocone SS316 dryer 50 L 1 No Air Compressor 70 CFM 1 No
Tray dryer 12 trays 1 No
Vacuum Tray dryer 6 Tray 1 No Corrosive Block
Tray dryer 24Tray 1 No FRP Reactor 2000L 1 No
Sifter 24“ 1 No Glass Lined Reactor 1600 L 1 No
Multi mill 25 Kg/Hr 1 No Glass Lined Reactor 630L 1 No
Sifter 12“ 2 No's Glass Lined Reactor 100L 1 No
Multi mill 10 Kg/Hr 2 No's Hydrogenator -SS316 -350L (25 Kg) 1 No
Cooling tower 70 TR 1 No Brine Compressor (-20 DEG) 15 TR 1 No
Cooling tower 30 TR 1No Cooling in
Global operations tower 165and
the USA TR India with project
1 Nomanagement,
Vacuum Pumps 300M3/Hr 4 No‘s Centrifuze
IP controlSS316 & halar
and local coat at
solutions 36“ 1 Noheadquarters
our USA
 Analytical Facilities
CiVentiChem, India
S. No. Name of the Instrument No. of Make
instruments
1 High Performance Liquid 2 Agilent
Chromatograph With PDA detector
2 High Performance Liquid 1 Agilent
Chromatograph With VWD detector
3 High Performance Liquid 1 Agilent
Chromatograph(RRLC) with PDA
Detector
4 Preparative HPLC 1 Agilent
5 Gas Chromatograph with FID Detector 2 Agilent
6 Liquid Chromatograph-Mass 1 Agilent
Spectrometer(LCMS) 1 Schimadzu

Global operations in the USA and India with project management,

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 Analytical Facilities
CiVentiChem, India
S.No. Name of the Instrument No. of Make
instruments
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
Global operations in the USA and India with project management,
IP control and local solutions at our USA headquarters
Case Studies

Global operations in the USA and India with project management,

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 Case Study #1
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 support
Made several hundred analogs for lead optimization
50-100 mg of each and purification by column chromatography
with our chemists on FTE basis
Continuous communication & collaboration throughout
Global operations in the USA and India with project management,
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 Case Study #2
Lead Optimization Through to Pre-Clinical Development
Start-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 laboratories
Ten-step synthesis & complex chemistry, including resolution
& asymmetric syntheses
Scaled-up and produced large volume of key Intermediates
Transferred the process to India
Produced product in India at significantly
Global lower
operations in the USA cost
and India with project management,
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 Case Study #3
Reference Standards and Intermediates
Mid-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 ring
Made 10 chiral carbohydrates involving 8-10 steps
Several heterocyclic building blocks
Handled sensitive reagents and manipulated protecting
groups. Global operations in the USA and India with project management,
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 Case Study #4
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 oC
Diels-Alder reaction, Michael addition
High pressure hydrogenation
Large-scale handing of sensitive reagents
Compound is now in Phase II
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 Case Study #5
Guidance, Consultancy and Intellectual Input
Virtual 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 discussion
Led to novel ideas & new synthetic schemes
Novel building blocks synthesized
New method development for pharma intermediates
Refined synthesis from 9 steps to 6 steps
New products & technologiesGlobal operations in the USA and India with project management,
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 Case Study #6
Large Scale Development and Manufacturing
Mid-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 steps
Produced in India & avoided production delays
Involved C-alkylation, anion chemistry, halogenation &
acetylation
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For inquiries, please contact:

Dr. Venugopal Rao Veeramaneni

CiVentiChem 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 : +91-40-23091692

Mobile: +91-9030026010;
e-mail : venu@indusbio.com www.civentichem.com
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THANK YOU
Venu

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