Discovery Services. Discovery. Biology. Toxicology DMPK. Medicinal Chemistry CADD

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1 Discovery Services Data Flow Biology Medicinal Chemistry Discovery CADD Toxicology DMPK

2 Discovery Services Who we are Sai Life Sciences is a Contract Research, Development and Manufacturing Organization focused on providing innovator pharma companies with drug discovery, CMC development and cgmp commercial scale manufacturing services. Our global pharma and biotech clients gain a clear competitive advantage through shorter time to both progressive development milestones and finally market launch. Synthetic & Medicinal Chemistry Services Sai employs a highly experienced team of over 225 synthetic and medicinal chemists, located in Hyderabad and Pune, to support the varied synthetic and drug discovery needs of our clients. Sai has a 15 year track record of providing high quality and value added chemistry services to > 80 clients from start-ups to big pharma. Biology Services Sai s In vitro pharmacology services include biochemical, cell based and ex-vivo assays. Sai offers In vivo biology models in oncology, inflammation, pain and metabolic disorders. Streamlined coordination with Chemistry, DMPK and Tox teams under the same roof. DMPK Services In vitro DMPK capabilities include metabolism and permeability studies, as well as measurement of various physico/biophysical properties. Sai s In vivo DMPK capabilities include rodent PK and numerous specialized techniques. We have accreditation from multiple international animal welfare agencies (AAALAC, OLAW & CPCSEA). Toxicology Services Non-GLP Toxicology capabilities in rodents include hematology, clinical chemistry, histopathology and toxicokinetics. Genotoxicology capabilities include AMES tests, micronucleus tests, chromosomal aberration tests and cell gene mutation tests. CADD Services We utilize a comprehensive suite of software and hardware to help understand and solve medicinal chemistry problems. We specialize in hit discovery, hit to lead optimization, lead optimization and chemoinformatics. Turbo Tech Transfer Turbo Tech Transfer (T3) is a new value added service Sai introduced to provide rapid access to kg batches of non-gmp drug substance for pre-clinical studies. This expanded service offering compresses the timeline inherent to transferring medchem processes for scale-up. Our goal is to meet your small production requirement, while anticipating the future needs of your program. As your NCE progresses through its initial phases of the molecular lifecycle, the T3 service enables rapid transition to future PR&D services and first in human cgmp batches. 2 discoveryservices@sailife.com

3 Make it Better Together At Sai, developing a business collaboration with our clients that benefits both parties is only the beginning. We have learned through experience, it is when we build a mutually beneficial partnership with a customer, that we can truly add the most value to important pharmaceutical programs. At Sai we will call this make it better together and it points at the additional value we aim to find in a long-term relationship. Amongst the most important elements of a successful partnership are communication and effective program management. To that end, we have built a team with an ingrained culture of supporting our clients and communicating progress. We ve implemented and clearly articulate our program management processes, while continuing to develop tools that better enable us working together for a successful outcome of every project. Website: 3

4 Synthetic & Medicinal Chemistry Services Why Sai? 15 year track record providing high quality and value added chemistry services to > 80 clients from start-ups to big pharma Delivery, flexibility and transparency make Sai a preferred partner for many clients (15 programs advanced to IND filing and beyond) Synthetic experience across a broad range of chemotypes including complex natural products Clear communication via trained project managers equipped with customized reporting tools Robust intellectual property protection via strict compliance policies & systems Availability of erooms and electronic laboratory notebooks Problem solving ability results in delivery of > 95% of all molecules requested Ready access to scientific literature via SciFinder and an extensive collection of journal subscriptions Streamlined coordination with Computational Chemistry, DMPK-Tox and Biology (all teams under one roof) Infrastructure 225 PhD & MS chemists (1 to 4 ratio) in 25 chemistry laboratories across 2 sites 50,000 ft2 of lab space Focused library synthesis lab with automated purification & evaporation Wide range of purification equipment and expertise (mg to kg) Dedicated analytical chemistry support team with key equipment: GCMS LCMS UPLCs SFCs HPLCs (PAD, ELSD & CAD) IR spectrometers UV spectrometers Polarimeters Multi probe NMRs Karl Fisher analyzer Melting point apparatus Thermo-gravimetric analyzer Powder X-ray diffractometer Differential scanning calorimeter Pune Laboratories Hyderabad Laboratories 4 discoveryservices@sailife.com

5 Synthetic Chemistry Capabilities Milligram to kilogram scale synthesis of client-defined compounds Focused compound libraries to support lead generation or optimization Preparation of building blocks, key intermediates and reference compounds Challenging chemotypes (up to 36 steps of targets with multiple stereocenters) Carbohydrates Phosphoramidites Lipids and PEG-chemistry Nucleosides and nucleotides Peptides and oligonucleotides Vitamin D analogues Steroids and prostaglandins Isotopically labeled compounds Drug conjugates (linkers & HPAPIs) Fluorescent & biotinylated compounds Medicinal Chemistry Capabilities Understanding multivariate SAR and problem-solving in lead optimization Rational drug design creating innovative lead compounds by optimizing: Metabolism PK exposure Cell permeability Aqueous solubility herg inhibition CYP & Pgp induction Time dependent & reversible CYP inhibition Potency & selectivity within the biological target class Website: 5

6 Biology Services Why Sai? 4 year track record of providing high quality and value added biology support services across multiple therapeutic areas Comprehensive in vitro and in vivo capabilities Clear and concise reports accompanied by raw data (customized to client requirements) Professional service with emphasis on excellent communication Streamlined coordination with Chemistry and DMPK teams to accelerate progress (all teams under one roof) Flexible and adaptive working style with fast turnaround times Screening throughput of >100 compounds a week per assay Infrastructure Pune Laboratories 15 PhD & MS biologists in Sai s Pune, India laboratories In Vitro Labs: Multimode readers Tecan Infinite M1000 Pro Plate Reader Flexstation 3 Tecan Freedom Evo 100 Liquid Handler Thermo Versette PicoReal qpcr instrument BSL2 cell culture facility Microbiology suite BARC approved radioactive facility In Vivo Labs: AAALAC Approved IVC cage systems Digital Randal Selitto instrument (pain models) Rotarod (motor coordination models) Incapacitance meter Grip strength meter Thermal hyperalgesia hot plate (pain models) Plethysmometer (inflammation assay) Von Frey instrument (pain models) 6 discoveryservices@sailife.com

7 In Vitro Pharmacology Capabilities Biochemical Assays Cell based Assays Protein-protein interaction Cell viability Binding Gene reporter Enzymatic Cytokine release Thermal shift Disease relevant Ex-vivo Assays Imaging Histology Biomarkers Tissue based In Vivo Pharmacology Capabilities Oncology Models Xenograft Syngeneic Metastasis PDX (coming soon) Inflammation Models Arthritis: CIA, CAIA, AIA Skin disorders: psoriasis, PMA-induced, AA-induced Pain Models Nociceptive: hot plate, tail flick, AA writhing, formalin test Neuropathic: CCI, chemo-induced Metabolic Disorder Models Genetic (db/db; ob/ob mice) STZI diabetic neuropathy Zucker fatty rats Website: 7

8 DMPK Services Why Sai? 8 year track record of providing high quality and value added DMPK support to a broad range of clients Accreditation from multiple international animal welfare agencies (AAALAC, OLAW & CPCSEA) Comprehensive in vitro and in vivo capabilities Clear and concise reports accompanied by comprehensive raw data (customized to client requirements) Professional service with emphasis on excellent communication and international logistical support Flexible and adaptive working style with fast turnaround times Streamlined coordination with Chemistry, Formulation, Tox and Biology (all teams under one roof) Infrastructure Pune Laboratories 24 DMPK scientists in Sai s Pune, India laboratories DMPK/bioanalytical equipment and facilities: In Vitro Labs: BARC approved radioactive facility API-4000 LC-MS/MS (2) API-4000 QTRAP LC-MS/MS with PDA UPLC/UV (3) In Vivo Labs: AAALAC, OLAW & CPCSEA approved for rats, mice, rabbits and guinea pigs Institutional Animal Ethics Committee (IAEC) similar to IACUC in USA Continuous and automated monitoring of temperature, humidity and air quality 8 discoveryservices@sailife.com

9 In Vitro DMPK Capabilities Metabolism Permeability CYP profiling PAMPA Metabolite ID Caco-2 Microsomal stability MDCKII / MDR1 Reactive metabolites Transporter studies Stability in hepatocytes Physico / Biophysical Salt form screening Plasma protein binding Pre-formulation development Aqueous and formulation stability Kinetic and thermodynamic solubility In Vivo DMPK Capabilities Rodent PK Mice and rats Plasma Brain Most other tissues Dog PK Beagles (at partner facility) Specialized / Cannulation Techniques Bile duct Portal vein Jugular vein Carotid artery Intraduodenal Enterohepatic recirculation Website: 9

10 Toxicology Services Why Sai? 8 year track record of providing high quality and high value Toxicology support to a broad range of clients Accreditation from multiple international animal welfare agencies (AAALAC, OLAW & CPCSEA) Complete compliance with internal Quality Assurance Unit to ensure integrity of our services and animal studies conducted with strict adherence to SOPs Clear and concise reports accompanied by comprehensive raw data (customized to client requirements) Professional service with emphasis on excellent communication and international logistical support Flexible and adaptive working style with fast turnaround times Streamlined coordination with Chemistry, Formulation, DMPK and Biology (all teams under one roof) Pune Laboratories Infrastructure 8 Toxicologists in Sai s Pune, India laboratories 8,000 ft2 animal facility with 10 isolated suites Laboratory: AAALAC, OLAW & CPCSEA approved for rats, mice, rabbits and guinea pigs Institutional Animal Ethics Committee (IAEC) similar to IACUC in USA Continuous and automated monitoring of temperature, humidity and air quality Bioanalytical Equipment: API-4000 LC-MS/MS (2) API-4000 LC-MS/MS QTRAP with PDA HPLC/UV (3) 10 discoveryservices@sailife.com

11 Non-GLP Toxicology Capabilities Single Dose Mice or rats Oral or parenteral dosing Observations recorded for 7 days post single dose Repeated Dose Hematology Clinical chemistry Histopathology Toxicokinetics Genotoxicology Capabilities AMES Tests Chromosomal Aberration Tests Full Assay Human lymphocytes in vitro Mini Assay Mice bone marrow in vivo Micronucleus Tests Human lymphocytes in vitro Mice lymphocytes in vivo Cell Gene Mutation Test HPRT assay Website: 11

12 CADD Services Why Sai? 5 year track record providing high quality value added computational chemistry services to a broad range of clients Comprehensive suite of software and hardware to help understand and solve medicinal chemistry problems Professional service with an emphasis on excellent communication Flexible and adaptive working style with fast turnaround times Experience in hit discovery, hit to lead optimization, lead optimization and chemoinformatics Associated consultant for Lhasa Limited (chemoinformatics) Infrastructure Graphics Processing Unit (GPU) workstations to support high end simulations and analysis Up to date databases for in silico screening purposes Commercial license to state of the art computational chemistry software: Lhasa Cresset ChemAxon Schrodinger Pipeline Pilot Discovery Studio Pune Laboratories 12 discoveryservices@sailife.com

13 Hit Identification Capabilities Focused library design Fragment based approaches High throughput docking of commercial libraries Virtual screening (focused or commercial databases) Structure and ligand based pharmacophore modeling Lead Optimization Capabilities Scaffold hopping Structure guided optimization SAR & R-group exploration and optimization Flexible docking & molecular dynamic simulations Compound selection based on customized property filters Cheminformatics Capabilities SAR and QSAR analysis ADME prediction modules Virtual library enumeration Medchem database design & maintenance Genotoxic Assessment (ICH-M7 Guidelines) Hepatotoxicity and other toxicity end point predictions Website: 13

14 Turbo Tech Transfer Drug Discovery & T3 in the Molecular Lifecycle Discovery Services Lead Evaluation Synthetic Chemistry Medicinal Chemistry Biology DMPK Top 3 Goals??? Lead Identification & Optimization Triage can comp Toxicology CADD Synthetic & Medicinal Chemists Biology, DMPK & CADD Experts 14 discoveryservices@sailife.com

15 What is T3? Turbo Tech Transfer (T3) is a new value added service Sai introduced to provide rapid access to kg batches of non-gmp drug substance for pre-clinical studies. This expanded service offering compresses the timeline inherent to transferring medchem processes for scale-up. Infrastructure: Focused team combining discovery and scale-up expertise EH&S / HAZOP support Dedicated non-gmp kilo-lab ( 100 L reactors) AR&D (as needed) Capabilities: Scale-up of APIs or scaffolds with minimal or no optimization Utilizing the knowledge and creativity of discovery chemistry merged with the expertise and experience of scale-up chemists Introduction of commercial raw material supplies where applicable Our goal is to meet your small production requirement, while anticipating the future needs of your program. As your NCE progresses through its initial phases of the molecular lifecycle, the T3 service enables rapid transition to future PR&D services and first in human cgmp batches. Turbo Tech Transfer (T3) Candidate Selection Early knowledge building for future development team 1KG 100L potential didate ounds Rapid scale-up of non-gmp tox batches Scaffold scale-ups to support MedChem Identify best candidates Prioritize backup candidates IND-enabling studies Convergent Route Scouting Blended Expertise & Technologies Synthetic, Process, Analytical & Formulation Chemists Tech Transfer & Supply Chain Experts DMPK & Tox Experts Website: 15

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