A Privately held CDMO head quartered in Hyderabad

1

A Privately held CDMO head quartered in

Hyderabad (Telangana, India)

Global Resource for Small Molecule Drug Discovery and Development

PHARMACEUTICALS | SPECIALTY CHEMICALS

11/19/2020Private & Confidential3

Innovation Center• Spread across in 1.3 Acres of Land with Built up Area of

50,000 SFT

• State-of-the-Art Infrastructure (Waldner Germany)

• Compliant with GLP Standards (Designed by Alexandria)

• Houses more than 250FTEs servicing drug discovery,

chemical and formulation process and analytical

development.

Introduction

LAXAI support customers

achieve their Goals by strong

emphasis on Safety, Quality,

Reliability, Innovation and

Efficiency by combining

World Class Research Talent

and Infrastructure with Cost

Advantage!


LAXAI has more than a decade of unparalleled experience in

Novel Molecule Discovery including Integrated Drug Discovery

and Medical Chemistry Services

Cost effective and reliable service - Process Development &

Clinical to Commercial Manufacturing of Drug Substance & Drug

Product

Strong collaborations across Pharmaceutical, Animal Health

and Specialty Chemical Companies

Leadership Team

Seasoned Entrepreneur with 17+ years of experience in Technology and Bio-Pharmaceutical Industries

Founder and ex-CEO of LAXAI Pharma Ltd -a Clinical Data Services company based in

New Jersey, USA

Ex Pfizer, Wyeth Pharmaceuticals, Johnson & Johnson and Deloitte

Established Innovative Service models in Health Care & Bio-Pharmaceutical Industries

Private & Confidential5

Vamsi Maddipatla

Chairman & MD

Worked at Uppsala University, Sweden; Institute of Molecular Medicine, India; Lupin Laboratories; Ranbaxy Laboratories, India

Co-inventor of Sudoterb (LL-3858), anti-TB Molecule for the Treatment of Pulmonary Tuberculosis (Phase-IIa)

His Leadership and Direction has cultivated remarkable growth in the Drug Development field within India which has resulted in two IND's and International Licensing deals in the areas of Benign Prostate Hyperplasia and Asthma

Co-authored 28 Publications & Inventor on 14 US Patents

Ram S. Upadhayaya, Ph. D.

CEO

15+ years of Experience in the Chemical & Pharmaceutical Industries, he has Built, Led and Managed Business Teams across Geographies covering various Portfolios and his focus is to Identify Critical Business drivers across Global Markets and in accordance with changing Market Dynamics.

He was previously associated with Piramal Pharma Solutions, Jubilant, & Dr. Reddy's Laboratories

Ganesh holds Masters in Business Administration and Bachelors in Chemical Engineering.

Ganesh Venkatraman

Global Head of BD

25+ years of Experience at various Leadership Positions in Biotech, CRO and Universities; Ex Karlsruhe Institute of Technology (KIT), Technical University of Dresden (TUD), JADO Technologies , Dresden, Germany, Jubilant Biosys, India

Delivered several leads, optimized leads and PCCs/DCs across Oncology, Pain, CNS, MD and Antibacterial Therapeutics Areas for Global Pharmaceutical Companies

Co-Inventor of Two Clinical Candidates ASN-001 ( NCT 02349139) for Metastatic Castration Resistant Prostrate Cancer & ASN-007 (NCT 03415126) for Metastatic KRAS, NRAS & HRAS Mutated Solid Tumors

Co-authored over 60 Publications/Patents (US/EU/Indian)

Raghava Reddy Kethiri, Ph. D.

CSO & Head of R&D

11/19/20205

Service Offerings

• Medicinal Chemistry

• Discovery Biology

• DMPK

• Integrated Drug Discovery


Discovery

• Drug Substance

• Drug Product

• Specialty Chemicals

• Clinical Trial Supplies

• Regulatory Support

• Key Starting Materials

• Intermediates

• Drug Substance

• Drug Product

• Specialty Chemicals

Development Manufacturing

Business Models


Full Time Equivalent (FTE) Collaborations

Flexible (FTE) Collaborations

Risk Sharing Collaborations

Fee For Service (FFS)

11/19/2020

Your Integrated

CDMO Services Partner

HandlingComplex

Chemistry

EHS and Quality consciousness

ISO 9001, cGMP Compliant Manufacturing

Facilities

Developing sustainable

supply chain

More than a Decade of Reliability in Process

Development and Clinical to Commercial supplies of

DS and DP

Experience

Integration of Teams and Facilities to enable Seamless Tech-transfer

and Scale-up from RSMs to APIs

Efficiency

Long-tenured Staff Working Closely

together and with you to Determine the Best

Path Forward

Collaboration

Ongoing Investment in Facilities and Personnel

to meet Continually Shifting Market needs

Investment

End to End CMC Solutions


Pre Clinical Phase I Phase II Phase III Commercial

Process R&D

Developability and Formulation Research

Analytical Development, Quality Control and Stability Studies

Global Regulatory CMC Filing Support

Drug Product

Analytical

Regulatory

11/19/2020

API & Intermediates Manufacturing

Formulation and Dose Form Development

Drug Product Manufacturing, Packaging and Labelling

Drug Substance

Drug Substance

• Starting Material

• Key Intermediates

• Beta Lactam Intermediates

• Active Ingredients

• High Potent APIs (HAPI)


Service Offerings

• State-of-Art Development Facility located in Hyderabad, India

• Decades of Experience in Developing and Scaling-up Intermediates, building Blocks and APIs

• Capability to Scale-up to Multi-tonnes

• USFDA, MHRA, EDQM Inspected Manufacturing Facility

• Network of Strategic Business Partners (SBPs)

Route Scouting and Process Development

Preclinical and Clinical Trial Scale-up and Manufacturing

Analytical Method Development, Validation and Transfer

Crystallization Study and Polymorph Screening

Process validation and Commercial Manufacturing

Regulatory Support and Filing

Focus Areas Development Expertise Manufacturing Expertise

Kilo Lab


• Flexible Reactor for quick change over -50L to 500L (SS,GLR, Hastelloy)

• High Efficient Distillation Facility

• Capability to handle Varying Temperature & Pressure Reactions

Includes:

Addition Control, High Vacuum Distillation with Columns of Different Sizes, Heating & Cooling Control, Data Logging, Clean Room Control with Building Management System

Dedicated Lab used for

the Process Development

and Scale-up and

Production of Complex

Intermediates and APIs up

to Pilot Scale

Unit 1: Pashamylaram, Hyderabad (India)


• Total Area: 29,582 Sq. M

• Built-up Area: 2,400 Sq. M (Vast Area Available for Expansion)

• Total Reactor Volume: ~148KL (100L to 8KL)

• 6 Production Blocks for Intermediates and 3 Clean Rooms

• WHO GMP Certified and Certified ISO 9001:2015

• Hydrogenation and Cryogenic Capability

o This Manufacturing Facility has vast experience in handling Bromination (Using Liquid Bromine), Chlorination (POCl3 Reaction), Fluorination (Using KF), Cyanation (Using KCN), and Grignard Reactions

o Our State-of-the-Art Facility supports our customers through Backward Integration of Supply Chain by Manufacturing Key Starting Materials and Intermediates

o The strong Tech Transfer team undertakes Processes from R&D to Manufacturing with “First Time Right Approach”

Process R&D | Analytical Capabilities | GMP Clinical Supplies (Phase I & II) | Custom Manufacturing of SM, KSM, Intermediates and Specialty Chemicals | Commercial Plant (100kg – Multi Tonnes)

Unit 2: Jeedimetla, Hyderabad (India)



• Built-up Area: 8,406 Sq. M

• Total Reactor Volume: ~163KL

• 8 Production Blocks for Intermediates and 5 Clean Rooms

• Hydrogenation and Cryogenic Capability

o Vast Experience with Process Validation, Regulatory Filing, and Supplying Drug Substance to Regulated Markets including USA, EU, Japan, and South Korea.

o This Manufacturing Facility provides flexibility in Batch Sizes (3kg to 100kg) owing to Available Reactor Sizes (50L till 3KL)

HPAPI Expertise


11/19/2020

Scale Facilities Batch Size Reactor Size Purification & Drying Protection

R&D

Pilot

Production

3 HPAPI Benches

OEB5

2 cGMP Kilo Labs

OEB5

1 cGMP Industrial

Suite OEB5

Gram Scale

From 0.25 – 5 Kg

Up to

50 Kgs

From 0.25 to 10L

Up to 25L

Up to 2000L

• Flash Chromatography

• Evaporator 2L

• 2 Filter Dryer (12L)

• 100L of Total Reactor Capacity

• 2 Filter Dryer (8 – 10L)

• Static Dryer 0.4m2

• 5000L of Total Reactor Capacity

• Filter Drying (550L)

• Finishing suite equipped with Multiple PSR options (Batch Size 1 – 100+ Kgs)

• Ventilated Hood with Gloves equipped with HEPA Filters and Glove Boxes

• Cleanroom classified ISO8 with independent HVAC

• Isolator / Glovebox

• Cleanroom classified ISO8 with independent HVAC

• Isolator / Glovebox

HPAPI Handling

cGMP HPAPI Production Suite

Manufacturing Facility

Drug Product

• Preclinical Formulations

• First In Human Formulations

• Clinical Phase 2 & Formulations

• Commercial Manufacturing


• State-of-Art Development Facility located in Hyderabad, India

• Decades of Experience in Integrated DS & DP Collaborations

• Oral Solids

• General Injectables

• High Potent OSD

• High Potent Injectables

Oral Solids & Injections

Handling Non-Contained & Contained Products

Preclinical, Clinical Trial Material and Commercial Manufacturing

Analytical Method Development, Validation and Transfer

Focus Areas Development Expertise Manufacturing Expertise

Service Offerings

High-Potent OSD & Injectables


Shameeerpet, Hyderabad (India)


• Built-up Area: 9,372 Sq. M (Oncology Block)

• WHO & EU GMP Certified

• Aseptic Filtration, Sterile Components Handling, Filling, Stoppering, Loading and Unloading for Freeze Drying and Sealing, Sterility Testing Area, Dispensing of API

• Compounding (Solution Preparation) is done in Isolator, Component Preparation, Vial Washing, Depyrogenation and Dispensing of API & Excipients

Tablets

Capsules

Liquid Injectables

Up to 150000 per hour

Up to 3000 per hour

3000-7200 vials per hour

360 Million Tablets

7.2 Million Capsules

12.6 Million Vials wrt 10ml Vial

Dosage Forms Planned Capacity Annual Capacities

High-Potent Oral Solids


• Integrated Containment Granulation Line -30 Kg capacity with Vibrosifter, HSMG, Wet Comill, FBD, Dry Comill

• Integrated Containment Granulation Line- 5 kg capacity with Vibrosifter, HSMG, Wet comill, FBD, Dry Comill

• Inter Exchangeable Octagonal Blender -75Lts and 150 Lts capacity (To handle 75kgs of batch at a time for Compression).

• A Capsule Filling machine integrated with Isolator for Charging and discharging of Capsules

• Fully Automated Coating machine integrated with Isolator for charging and discharging of Tablets (To handle 15kg Minimum and

56kg Maximum batch size)

High-Potent Injectables


• Compounding vessels (30 L and 100L) and Filtration vessels (30 L and 100L) integrated with Compounding Isolator and Filtration Isolator.

• Integrated line equipment's Rotary Vial washing machine, Sterilizing and Depyrogenating Tunnel, Vial filling and Bunging Machine with

capacity 120 Vials / Min of 10ml size are common for both liquid and Lyo Line.

• Automatic Lyo loading and unloading system are considered for ease in operation and to reduce manual interventions during handling.

• Lyophilizer -1 with capacity 10000 Vials of 10ml capacity and Lyophilizer -2 with capacity 2500 Vials of 10ml capacity

Project Management

Private & Confidential19 11/19/2020

Project Manager

Process Engineering

• Process Scale-up

• Technology Absorption

• Transfer and Execution

Analytical R&D

• Analytical Method Development & Validation

• Analytical Method Technology Transfer

Shared Support Functions

• Quality Assurance

• Regulatory Affairs

• Supply Chain

• Production

Process R&D

• Route Scouting

• Process Familiarization &

Development

Environmental Health & Safety (EHS)

Private & Confidential20 11/19/2020

ENVIRONMENT

HEALTH SAFETY

Regular Audits on:

Chemistry Labs & Night

Safety Usage and Storage of

Pyrophoric / Poisonous

Chemicals Segregation of

Hazardous Chemical Waste

Management Onsite

Emergency and Business

Contingency Plan

Compliance with EHS related

Law of Land

Dedicated Safety Officer In-Charge of EHS and Safety Committee

Devising and Implementing EHS SOPs

Review of Safety

Performance and Safety

Audit Investigation of any

Incident and taking

Necessary Corrective and

Preventive Actions

Summary


More than a decade of experience in offering end-to-end CMC Solutions

One Stop Shop CDMO Service provider for Integrated DS & DPDevelopment and Manufacturing

State-of-the-Art R&D Infrastructure coupled with GMP Manufacturing

EHS and Compliance to Quality and Regulatory - an Integral part of ourOrganization Culture

Case Studies

Early Integrated CMC Development

• Drug Candidate’s Molecular Properties

• Physicochemical Characterization including Crystallization Screening, Salt Screening

(if required), and Polymorph screening (if required)

• Improving the Medicinal Chemistry Process

• Analytical Method Development and set Specifications (report results)

• Synthesizing the required quantities for Pre-Clinical Toxicology Study – GMP setup is not

essential unless client wants the material to be used for Phase-I Human Studies as well

• R&D Stability Study – 6 Months Stability Data

• Documentation to Support IND Filing


At IND-Enabling-Study Stage, our Focus is Primarily on:

LAXAI Discovered Molecule taken for further Development

followed by Supplies towards Toxicology Studies


• Removed Column Chromatography for all 3

stages

• Process Optimized by Screening different

Catalysts, Bases, Solvents, Ligands and

made work up Modifications

• Process was scaled-up successfully and

timely to deliver the NCE to support

Toxicology studies

• Further process improvements underway to

scale up the NCE to multi kilo scale

including application of Green chemistry

• The physicochemical aspects of the NCE are

under development including polymorph

and salt screening for pre-formulation

• Develop a Scalable 6 Stage Process in

12 Weeks and Demonstrate the

Optimized Process on 1kg Scale.

• Total Project Timeline was less than 20

weeks.

• 3 Column Purifications (2 Silica & 1

Alumina), Multiple Process Impurities

and related substances (des-Fluoro,

dimers, trimers) at 2 Stages

• To Scale-up the existing Medicinal

Chemistry Process with minimum

Process Development and Synthesize

Small Molecule JAK2-BET Inhibitor and

support for Toxicology Studies.

Goal Challenges Achieved

11/19/2020

Phase I / II Clinical Stage

• Developing a Synthetic Process that avoids overly Hazardous Reagents and avoids Intermediates with Genotoxic Potential, Smart selection of Regulatory Starting Materials and applied Scalable Chemistry

• Key/Critical Quality Attributes (such as purity/impurity) will require Defined Specification Limits that are supported by Toxicological Study Data

• Forced Degradation Study and Structural Elucidation Study

• Analytical Method Development and Method Qualification

• Specifications – Report Results

• Impurity Tracing and Impurity Levels at each Stage will be defined, justified and supported by the Impurity Test Method associated with the Material.

• Impurity Levels outside of ICH Guidelines will include a Toxicological Justification, as well as appropriate Manufacturing Controls to Limit this Impurity or justification as to why Manufacturing Controls cannot Limit the Impurity

• One or more GMP Batches to Supply Phase-I (in some cases, Multiple Phase- I Studies) Clinical Study from a GMP Facility (Optional – FDA Audited Facility)

• GMP Stability Study (ICH stability)

• CMC Documentation: Discuss the Composition, Manufacture and Control of the DS


At Phase I / II Stage, our Focus is Primarily on:

KSM Development and Manufacturing Project for an

European Big Pharmaceutical Company


• High-Vac Distillation (HVD) was avoided

with Derivatization as Oxalate Salt

• Process Optimization with DoE Approach,

considering Variables like Time,

Temperature, Catalyst Loading, Types /

Grades of Catalysts, and Identified the

Right Conditions to achieve below 0.3% of

Des-Halo Impurity

• The overall Yield was Improved by ~15%

• Subsequent to Development which took

about 10 weeks, 28 Kg was Delivered in

about 15 weeks with < 0.3% Des-Halo

Impurity including the 1kg Demo Batch

• Process and Analytical Development –

Phase Appropriate

• 1kg of Sample to Customer as Proof of

Process Scalability followed by

Manufacturing of 25kg of KSM for

Phase-I/ II Clinical Studies in 28 weeks

• Critical Expectation: Controlling Des-

Halo Impurity below 1% which was

tightened to less than 0.5% during the

course of the Project

• To optimize the customer’s Lab

Process and Eliminate thin Film

Evaporation (TFE), High Vacuum

Distillation (HVD) and Supply of (25kg)

in 28 weeks

• (KSM for Phase-I / II)


11/19/2020

KSM Development and Manufacturing Project for a

USA based Pharmaceutical Company


• Stage Specific DoE in Asymmetric Crossed Aldol

Reaction to Improve the Anti Selectivity (80:20 Vs

94:6)

• Eliminated Column Chromatography at 3 Stages –

Optimization by Reagent Screening, Work up

Modifications, Telescoping with Appropriate

Process Controls; Overall Batch Cycle Time

Reduced by ~30%.

• Overall Yield of the Process Improved from 10% to

25% and Lead Time of the 20 Kg Material Reduced

from Proposed 20 weeks to 12 weeks for future

Campaigns.

• Process was Executed Successfully and Delivered

22Kg of the Intermediate in 28 weeks as

Committed.

• Cost of the Intermediate Reduced by 25% as it was

important owing to KSM’s Cost Contribution in the

Final API Cost

• Develop a Scalable 7 Stage Process

and Demonstrate the Optimized

Process on 20Kg Scale in 30 Weeks

Time

• 6 Column Purifications, 1 Diastereo

Isomer, 1 Enantiomer, Multiple

Process Impurities and Related

Substances (over Reduced Impurity,

Dimers, Trimers) at 4 Stages

• Functional Groups are Prone to

Degrade in Presence of Acidic Traces

• To Optimize the Existing Medicinal

Chemistry Process and Improve

overall Yield of Small Chiral Aryl

Unsaturated Molecule and

Continuous Support for Phase-II Trials


11/19/2020

Phase-I Clinical Supplies for a Pharmaceutical Company in West

Coast (USA)


• No prior process description as was

handled in an academic setup. So

familiarize the process and further

optimization with specific focus on

optimizing the reaction conditions,

and isolation of intermediate steps

• Development of the crystallization

step yielding the desired polymorph

• Tracking and tracing of the impurities

followed by impurity purging studies

• Analytical method development and

method qualification

• Process was scaled-up successfully

and timely to deliver the NCE to

support multiple Phase I studies

• Familiarize the Process and Synthesize

3 X 30 gm Demo Batches

• Phase appropriate Process

Development – Sufficient for a GMP

Scale-up

• Develop Analytical Methods and

Qualify the Methods

• 4.5kg GMP Batch

• Familiarize Existing Process (previously

synthesized about 100gm in an

academic setup) and further Optimize

the Process before Manufacturing a

GMP Batch


11/19/2020

Phase-III Clinical Stage & Regulatory Filling Support

• Improvement in the Synthetic Process with the Aim of Reducing the COGS

• Finalization of the Synthetic Scheme

• Tracking and Tracing of the Impurities followed by Impurity Purging Studies

• PGI Evaluation and Showing Cut-off

• Finalize API Specifications

• Analytical Method Validation & Pilot Batch Manufacturing

• Process Robustness Study while Applying the Principles of QbD (Quality by Design)

• Preparation of Validation Protocols followed by Process Validation

• Formal Stability Study (as per ICH Guidelines)


At Phase III Stage and Looking at a Possible Commercialization, our Focus is Primarily on:

Phase-III Clinical Supplies for a Small Pharmaceutical Company


• Process Familiarization Including Feasibility run

for Alternate Chemistry to avoid Cryogenic

Reaction

• Process Development and Incorporating

Controls as appropriate

• Replace Spray Drying Process with ATFD – to

Produce Amorphous Material

• Impurity Fating Studies including PGI Evaluation

and Showing Cut-off

• Analytical Method Development and Method

Validation

• Pilot Scale Manufacturing followed by Risk

Assessment Studies

• Process Validation followed by Formal Stability

Studies

• CMC Support for Regulatory Filing with USFDA

and EMA

• Familiarizing the Current Process as-is

in Order to showcase Reproducibility

and no Adverse Safety Issues while

handling the Raw Materials and

Intermediates

• Process Optimization & Process

Validation

• CMC Support

• Develop the Process for the Active

Ingredient, Validate the API

Process, Manufacture Registration

Batches, and Provide Regulatory

Support for Registration of the

Product with USFDA, and EMA


11/19/2020

KSM Development and Manufacturing Project for an European Mid-Size Pharmaceutical Company


• Removed Additional Purification Stage –

Optimization by Reagent Screening,

Modifying work up Modifications and

Controlling Regio Isomers by Optimizing

Reaction Conditions

• Reduced the Effluent Load - by

Optimizing Solvent quantity and eq. of

Reagents and established the Control for

des-chloro Impurity through DoE Study

• Reduced the Solvent Consumption by

70% and BCT reduced by 35% for

Campaign 2

• Overall Yield of the Process Improved

from 60% to 72% in Campaign 2

• Cost of the Intermediate reduced by

~25% with Yield Improvement.

• Develop Scalable 2 Stage Process in

about 8 weeks time and Demonstrate

the Optimized Process on at least 100

Kg Scale. Total Project Duration – 24

weeks

• Multiple Regio Isomers, Multiple

Process Impurities (des-chloro

Impurity, Azo and Azoxy Compounds),

Additional Purification to Improve the

Color, which accounts to 30% Yield

Loss

• Limitations on Batch Size, Effluent

Generation, and High Batch Cycle

Time

• To Optimize the Existing Process and

Improve overall Yield of Poly Amino

Aryl Compound and Manufacturing of

3 X 100 kg Campaigns


3rd Floor, Ventureast Plaza, Plot No. 40-41, Road Number 2,

Financial District, Nanakramguda,

Hyderabad – 500 032, Telangana, INDIA

Corporate Office

Building 900, MN Park, Synergy Square I,

Genome Valley, Turkapally,

Hyderabad-500 078, Telangana, INDIA

R&D Operations

4010 Moorpark Ave,

Suite 226, San Jose,

CA 95117, USA

Ganesh VenkatramanGlobal Head, BD & CDMO

[email protected]

(+91)-910-090-7013

mailto:[email protected]

Documents

A Privately held CDMO head quartered in Hyderabad