Integrated Drug Discovery Founded on 18 Years of Deep Experience and Delivery of Milestones

Version 3.2: 13 Sept 2019

1

Target to Lead Generation

Lead Optimization Candidate Selection (IND)

Structural Biology (Protein Science, Crystallography)

Medicinal and Computational Chemistry

Screening & Profiling Early ADMET & PK In vitro / In vivo Pharmacology

Medicinal Chemistry DMPK SBDD (Co-crystallization,

Computational Modelling) Target Engagement & Disease Models Safety Profile and Genotox Preformulation

Integration of Discovery Process Designed for Speed to Milestones…

1

Non-GLP & GLP Tox Process Development Scale-up & cGMP API D2M Predictions (WinNonlin)

Disease Biology Expertise, Optimization of Drug Like Properties

Oncology Metabolic Disorder CNS Pain & Inflammation (P&I)

22

Deep experience and IT tools to analyse and extract information for next cycle design Cycle

time

Deep understanding of molecular interactions, structure & product properties to enable simultaneous multi-parameter optimisation design

Biochemical ,cellular and in vivo testing. ADME testing

Rapid and efficient synthetic execution

Optimization Cycle Designed for Speed in Decision Making, Bringing it All Together

Supported by Technology Platforms

33

Emerging Technologies to Foster Speedy Execution

…accelerating decision making for our clients’ programs

Flow Chemistry unit, faster, safer and more flexible synthesis with increased speed and improved quality

SPR, label free real time detection of bimolecular interactions

RapidFire, high-throughput screening system

AI/ML Platform, in depth data analysis, drug repurposing, target identification and validation

Orbitrap for met ID

44

Three Case Studies Showing our Strengths in…

• Speed From no chemical matter to successful IND in 3 years In-silico hit to preclinical candidate in 18 months

• Integration of our technology platforms to deliver with speed Computational chemistry, structural biology, rapid throughput of assays

• Medicinal chemistry design skills Capability to design successful compounds even when no chemical matter is known

• Full integration Integration of disciplines to deliver high quality clinical candidates in a speedy manner RapidFire, high-

throughput screening system

• An AI/ML platform for all disciplines AI/ML Platform, in depth data analysis, drug repurposing, target identification and validation

5

Oncology Case Study – First-in-Class Mechanism, Preclinical Candidate in 18 Months…

5

Discover orally available small molecules to address unmet medical needs in oncology

Delivered a pre-clinical development candidate for oncology and two other lead series in 18 months

Homology model/ Virtual screening

Rational design+ Structural biological analysis

Pre-clinical development candidateTarget

Objectives

Deliverables

2017 18 Months 2018

synthesis and evaluation

Accelerated execution

6

Oncology Case Study– Unmet Need, Delivered to IND Stage…

6

Delivered non-steroidal hit (3) and lead series (2) plus a clinical candidate as well as a backup candidate Deliverables

SVP, Endo Pharma “I congratulate the Jubilant and Endo teams on achieving this important milestone. It was their outstanding collaborative work and ingenuity that enabled the successful filing and acceptance of an IND in less than

three years

Target IND3 Years

7

SBDD Case Study – Unmet Needs in Metabolic Disorders (GPCR)

• Delivered ahead of contracted timeline• Hits identified from SBDD studies when HTS failed to identify hits, molecule in clinic• 3 Milestones achieved

Delivered Hit series, Lead compounds and one Clinical candidateDeliverables

7

Publication: The Discovery, Preclinical, and Early Clinical Development of Potent and Selective GPR40 Agonists for the Treatment of Type 2 Diabetes Mellitus (LY2881835, LY2922083, and LY2922470); J Med Chem. 2016 Dec 22;59(24):10891-10916;

8

Oncology: Deep Experience Resulting in 17 Milestones…

8

In-vitro assays•Cell free biochemical: TR-FRET, AlphaLISA, ADP-glow

•Target modulation: Autophos, ELISA, alpha-screen, MSD,

Western Blot, flow cytometry, PCR

•Cell Cycle: FACS analysis; Cell migration

•Matrix Invasion: Matrigel and HUVEC

•Proliferation & Apoptosis: Alamar blue, Annexin V,

caspase activation

•Immune modulation: Immune-profiling, T cell proliferation

and co-culture

•Others: FLIPR, ICC, 3-D culture, assay for epigenetic target

In-vivo models

•Orthotopic (Breast, Prostate, SCOT, Glioblastoma)•Syngeneic (B16-F10, CT26 and 4T1)•Matrigel plug angiogenesis

• 25 Programs • Disease pathways /mechanisms

• RTKs, PI3K/AKT, MAPK, enzyme and others• Epigenetics, Kinases, Immuno-Oncology and

GPCRs• Specific tumor types, prostate, NSCLC,

hematological tumors and others

Xenograft (Subcutaneous) models for PK-PD or efficacy

Lung (NCI-H82, HCC827, Calu-6) Breast (MDA-MB-231)

Ovarian (A2780)Colon (HT-29, Colo-205, HCT116; LoVo)

Prostate (PC3, DU-145) Pancreatic (PANC-1; Bx-PC3)

Gastric (MKN-45) Melanoma (A375)

Hematological cancers (MV-4-11, Pfeiffer, CCRF-CEM, MM1.S)

Other tumors (A431, U-87

MG)

9

Metabolic Disorders: Expertise in First-in-class Targets with Novel Mechanisms of Action

9

In-vitro assays•Assays: Insulin secretion, glucose uptake, glucagon secretion,

incretin release [GLP-1, CCK, PYY, GIP] beta cell protection;

Adipogenesis, adipolysis; Apo B secretion, fatty acid oxidation;

membrane potential; Transporter; assessment of Gene/ Protein

modulation

•Cells: Islet, Hepatocytes, Muscle

•Cell Lines: Min6; STC-1; 3T3L1; C2C12; L6

•Platforms: High Content Imaging; MSD; ELISA; RapidFireLCMS/MS; Simple Western; Western Blot; Immuno-cytochemistry

In-vivo models •Streptozotocin-Type 1 diabetic; STZ-induced diabetic neuropathy; STZ

induced Diabetic Nephropathy

•DIO: body weight, glucose, insulin, lipids, and pair-fed studies

•Genetic:ZDF, ob/ob, db/db

•Incretin and endocrine secretion: [GLP-1] in mice

•Acute and Chronic: OGTT, IPGTT (Glucose & Insulin) in mice and rat

•Acute: malonyl CoA lowering in rats

•Lean diabetic: (STZ + Nicotinamide)

•NASH: DIO plus methacholine deficient diet

• 16 Programs • Milestones achieved - 11 • GPCR’s, Kinases, Enzymes and Ion channels

Recent Publication: A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders; Sci Rep. 2018 Feb 26;8(1):3660;

10

Pain and Inflammation (P&I): Focus on immuno-inflammation

In-vivo models

10

• 13 Programs • Milestones achieved - 8• Ion channels, GPCR’s, Kinases and Enzymes• Collaborated with top pharmaceuticals and

biotech’s to target various pain pathologies

Recent Publication: Synthetic analogues of the parasitic worm product ES-62 reduce disease development in in vivo models of lung fibrosis; Acta Trop. 2018 Sep;185:212-218;

• Neuropathic Pain models: CCI induced neuropathic pain

in mice and rats , L5/L6 ligation(SNL), SNI in mouse,

Paclitaxel induced pain (cancer), Bone cancer pain, STZ

induced Diabetic Neuropathy;

• Inflammatory Pain models:

Formalin, CFA,

Carrageenan

• Inflammatory Bowel Disease: DSS, TNBS and

oxazalone-induced colitis in mice (acute and chronic)

• Arthritis: Collagen induced

arthritis

• Respiratory and Atopic Allergy Models: Steroid sensitive

and resistant asthma in mice; LPS-induced neutrophilia

in rats

• Fibrosis Models: Lung,

liver, skin, kidney, NAFLD

and NASH

• Others: Psoriasis, EAE (MS model), Uveitis in rabbits,

rats & mice(ocular models)

• PK-PD correlation

In-vitro assays• T-cell proliferation; T- cell migration;

immune (multiplexing, MSD

platform); IKK and NF-κb reporter;

JAK-STAT pathway; Kinase [PI3K,

AKT, P38; MAPK, JNK];

Chemotaxis

• Rat macrophage culture and

multiple cytokine measurement

using MSD technology

• In vitro microglia and astrocyte

culture from rodent brain and

functional

• CGRP release from spinal

neurons, Neurite outgrowth,

neuroprotection and toxicity

• Protein translation, Multiple

unfolding protein response (UPR)

assays

11

CNS: Deep Expertise - Neuro-Degeneration, Psychiatry, Neuro-Inflammation

In-vitro assays•In vitro microglia and astrocyte culture from rodent brain and functional (measurement of IL1b, IL6 and TNFa)

•Phospho-tau and Amyloid beta measurement using MSD or ELISA

•CGRP release from spinal neurons

•Neurite outgrowth, neuro-protection and toxicity

•Protein translation

•Multiple unfolding protein response (UPR)

•Several screening platforms covering wide target class

•Numerous cellular using iPSC neurons from AD patients

In-vivo models •Neuro-degeneration: Amyloid beta isoform, total and phospho-tau, UPR signaling, stroke, wire knife employed surgical

•AD mouse model: access to transgenic mice APP, tau and others from Taconic

•Cognition: Novel Object Recognition Task [NORT]

•Psychiatry: Forced swim test

•Neuro-inflammation: Mog induced MS

•Target Engagement: Several ex-vivo binding target modulation

•PK-PD correlation

11

• Collaborated with big pharma, biotechs and start-ups

• Worked across spectrum of target classes including Ion Channels, Kinases, Enzymes, Transcription Factors

1212

Our Talent Base

Overall Ph.D. ratio across Chemistry, Biology, DMPK: approximately 15% and increasing

Researchers with overseas experience at, for example

Pfizer, Bayer, Novartis, ETC Singapore, NCI Frederick, etc.

Max Plank Institute, Lawrence Berkley National Lab., Harvard U., etc.

Recruiting from diverse backgrounds and nationwide in India

Low turnover (10-15%), especially at the Ph.D. level ( <5%)

13

Thank You for your Time

Our Values

For More Information: bd@jubilantbiosys.com

We invite your comments and how can we speed up your discovery…

“Jubilant Biosys is excited to jointly explore your areas of target interest and

how we can complement your efforts to bring your programs to IND and Clinic

quickly”.