Type II Diabetes Mellitus

IQ4I Research & Consultancy Pvt. Ltd.

Type II Diabetes Mellitus

Pipeline Analysis

CONTENTS� REPORT DESCRIPTION

� INTRODUCTION� Causes & Symptoms

� Diagnosis

� Unmet needs

� Epidemiology

� Current therapies

� HOT TARGETS, MECHANISMS & THERAPIES� Novel Disease mechanisms &

therapies

� Leading & hot targets of T2DM

� SMALL MOLECULES� Pipeline� Competitive Analysis

� LARGE MOLECULE � Pipeline� Competitive Analysis

� MONOCLONAL ABs� Pipeline� Competitive Analysis

� STEMCELL THERAPY� Pipeline� Competitive Analysis

� RNA-BASED THERAPY� Leading & hot targets of T2DM

� Novel targets of Diabetes

� T2D disease progression biomarkers

� MARKET DATA� Forecasting model

� Market dynamics

� Market sizing

� Cost burden

� PIPELINE ANALYSIS� Development stage

� Leading players

� Therapeutic segmentation

� Innovative approaches

� Target analysis

� RNA-BASED THERAPY� Pipeline� Competitive Analysis

� GENE THERAPY� Pipeline� Competitive Analysis

� RECOMBINANT FUSION PROTEINS� Pipeline� Competitive Analysis

� DRUG ANALYSIS BASED ON MECHANISM

� MAJOR PLAYERS� Company Profiles

� Overview, Pipeline & Deals

� REFERENCES

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� “Type 2 Diabetes (T2D) Pipeline Analysis” gives comprehensive insight on the variousdrugs being developed for the treatment of T2D. The report covers all the drugs beingdeveloped in various phases (Discovery, Preclinical, Clinical & Marketing). The pipelinefocuses on novel pharmacologic drugs & regenerative medicines covering small molecules,monoclonal antibodies, stem cell therapies, Gene therapies, Recombinant proteins andRNA-based therapeutics, but excludes symptom relief drugs, generic combinations. Thereport also covers some of the hot targets in research for T2D treatments and diseaseprogression biomarkers.

� This report enables Pharmaceutical /Biotech companies, Academic institutes, Individualresearchers, Investors, Medical technology companies, Service providers and other

REPORT DESCRIPTION

researchers, Investors, Medical technology companies, Service providers and otherassociated stake holders to identify and analyze the available licensing/collaborativecommercial opportunities in the Type 2 Diabetes (T2D) Drug market. The report alsoprovide strategic insights on medicines that are likely to have an impact on T2D treatmentspace and potentially alter standards of care in T2D in the foreseeable future.

� Current therapies are focused on the treatment of hyperglycemia than on pancreatic Betacell dysfunction and they lose efficacy over time as both endogenous insulin secretion andinsulin sensitivity decrease. There is a need for type 2 diabetes therapies that act in concertwith available agents to provide adequate glycemic control without causing hypoglycemiaand weight gain, which are associated with increase in cardiovascular risk. Hence, itprovides a tremendous opportunity for upcoming therapies specific to T2D such as MAbs,stem cell-based, gene therapies and RNA-based therapies. These modalities may providebeta-cell protection, regeneration, mass increase with additional benefits of weight loss,triglyceride lowering and kidney protection.

TYPE II DIABETES - INTRODUCTIONType 2 Diabetes Mellitus formerly known as noninsulin-dependent diabetes mellitus(NIDDM) and adult-onset disease is a metabolic disorder which is characterized by reducedinsulin sensitivity, insulin resistance and pancreatic β-cell dysfunction

Prevalence

Urban ,

64%

Rural, 36%

Diabetes Affects

Diabetes Facts

•Globally, around 371 millionpeople are living with diabetes andtype 2 diabetes accounts for 90% ofall diabetes cases.•Currently, highest number of

•Non Hispanic Whites= 7.6%•Asian Americans = 9%•Hispanics = 12.8%•Non Hispanic Blocks = 13.2%•American Indians/Alaska Natives = 15.9%

People at major risk

Africa-13.5M

Europe–49.5 M

South East Asia-63M

North America-34.2M

South & Central America–23.4M Western Pacific-

118.8M

Middle East & North Africa– 30.6 M

Prevalence•Currently, highest number ofpeople with diabetes occurs in 40-59 years age group.•As of March 2013, approximately23 million children & adultswere observed with T2D.•Expenditure on diabetes in NorthAmerican region was higher thanother region. And by 2050, 1 in 3American adults will havediabetes.•In 2013, International DiabetesFederation (IDF) estimated 10million people with diabetes inChina, India, USA, Brazil &Russian Federation .

TYPE II DIABETES - CAUSES AND SYMPTOMS

Causes Symptoms

� Overweight

� Obesity

� Genetic susceptibility

� Increased thirst & hunger

� Dry mouth

� Polyurination

� Unexplained weight loss

� Fatigue

� Blurred vision

Risk factors

Family history of diabetes � Blurred vision

� Headache

� Loss of consciousness

� Slow healing sores/cuts

� Decreased vision

� Impotency

� Frequent yeast infections

� Acanthosis nigricans

� Numbness & tingling of hands & feet

� Family history of diabetes

� Unhealthy diet

� Increasing age

� Overweight/Obese

� Physical activity

� Ethnicity

� Poor nutrition during pregnancy

� Impaired glucose tolerance

� Pre-diabetes condition

� Polycystic ovary syndrome

� Genetic susceptibility

TYPE II DIABETES - DIAGNOSIS

BLOOD TEST

BLOOD TEST

BLOOD BLOOD

DIAGNOSISDIAGNOSIS HEMOGLOBIN A1C

HEMOGLOBIN A1C

LIPID TESTLIPID TEST

BLOOD CREATINI

NE & URINE

MICROALBUMIN

BLOOD CREATINI

NE & URINE

MICROALBUMIN

TYPE II DIABETES - UNMET NEEDS

Current type 2 diabetes therapies are focused on the treatment of hyperglycemia, a symptom, and not the direct cause of the disease, which is pancreatic Beta cell dysfunction.

Existing agents lose efficacy over time as both endogenous insulin secretion and insulin sensitivity decrease.

There is a need for type 2 diabetes therapies that act in concert with available agents to provide adequate glycemic control without causing hypoglycemia and weight gain, which are associated with increases in cardiovascular risk.

Need for new glucose-lowering drugs that act independently of insulin, have benefits beyond glucose-lowering actions, and provide improved tolerability compared with traditional medications for T2DM.

TYPE II DIABETES - COUNTRY-WISE PREVALENCE

USA X MN

Russia Federation X MN

Japan X MN

PakistanX MN

EgyptX MN

{MN: Million}

Fig 1

India X MN

ChinaX MN

BrazilX MN

MexicoX MN

IndonesiaX MN

X MN

Globally, the rate of prevalence is higher in men than in women and increases as age progresses.

CURRENT THERAPIES OF TYPE II DIABETES MELLITUSCurrent therapies for T2DM are relatively effective in controlling hyperglycemia. Some examples include:

Current Therapies

• Thiazolidinediones • Insulin secretagogues

•Sulfonylurea derivatives • SGLT-1/2 inhibitors

• α-glucosidase inhibitors • Insulin sensitizers

• Glucagon-like peptide-1 receptor agonists • Pyruvate dehydrogenase inhibitors

• Dipeptidyl peptidase-4 inhibitors • Fibroblast growth factors

• Long-acting DPP-4 inhibitors • Glucokinase activators • Long-acting DPP-4 inhibitors • Glucokinase activators

DIABETES: HOSPITAL READMISSION RATES IN U.S. (2011)

30-day readmission rate for patients aged 18-64 years (2011):

Type Total Readmission rate (%) Total cost of readmission rate (%)

Medicaid Patient 3.5% 3.3%

Privately insured patient 2.1% 1.7%

Uninsured patient 4.6% 4.1%

TYPE 2 DIABETESTYPE 2 DIABETESMARKET DATAMARKET DATAMARKET DATAMARKET DATA

T2D MARKET: FORECASTING MODEL

Historical Data

and trends of

T2D Market

Evolution

Company

Developments

Applications

Download Pattern

Regulatory

Landscape

Pipeline

Evolution

T2D Costs of

Burden

Hospitalization

Pattern

Readmission

Pattern

Market ShareEpidemiology

Pattern

Geographical

Usage

Market Restraints

� High cost of drugs and

innovative therapies

Market Drivers� High unmet need

� Increasing incidence of

Market Opportunities� Acquisitions/collaborations

of companies and research

institutes

Fig 2

Factors Influencing

Market Growth

innovative therapies

including stem cell

and gene therapies

Investments�In 2011, Eli lilly and Boehringer Ingelheim formed a diabetes

alliance whereas in 2013, both the partners adjusted the scope of

diabetes alliance with respect to LY2605541 for commercialization.

Increasing incidence of

diabetes and diabetes related

disorders

� Increasing aged population

� Alteration in lifestyle

.

Historical Market Data

Impact Analysis of Market

Trends

Market Size & Forecast by

Region

Major Players Profiling and

Strategies

Global T2D Market Size

2013 and Forecast to 2018Market Trends and

Forecasting

Market Penetration

�Innovative drug discovery

platforms

institutes

�Demand for novel drugs to

increase revenue of pharma

industry

T2D : MARKET DYNAMICS

�High cost of drugs and innovative

therapies (stem cell and gene

therapies)

�Risk of pancreatitis, pancreatic &

thyroid cancer associated with

incretin based therapies

RESTRAINTS

�High unmet need

� Increasing incidence of diabetes and

diabetes related disorders

� Increasing aged population & obese

� Alteration in lifestyle

DRIVERS

Fig 3

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thyroid cancer associated with

incretin based therapies

� Patent expiration of small

molecules

�Entry of basal insulin biosimilars

pose significant threat

THREATS

diagnosis� Acquisitions/collaborations of

companies and research institutes

�Demand for T2D drugs in emerging markets

�Innovative drug delivery platforms

OPPORTUNITIES

Global T2D

Market

T2D - MARKET SIZING

Global T2D Drugs Market Global T2D Drugs Market by Region

Fig 4 Fig 5M

ark

et s

ize

($B

illi

on

)

Mar

ket

siz

e ($

Bil

lio

n)

2014

2021

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• The global T2D market is estimated to be $XX billion in 2014 and is expected to reach $XX billion

by 2021 with a CAGR of X% (2015-2021).

• The market growth is attributed to increasing incidence of diabetes and diabetes related

disorders, high unmet need which led to development of innovative drugs in the market, emergence of

novel therapeutics.

2014 2015 2016 2017 2018 2019 2020 2021

Mar

ket

siz

e ($

Bil

lio

n)

Year

NA EU AP ROW

Mar

ket

siz

e ($

Bil

lio

n)

Region

TYPE 2 DIABETESTYPE 2 DIABETESPIPELINE ANALYSISPIPELINE ANALYSISPIPELINE ANALYSISPIPELINE ANALYSIS

T2D PIPELINE BY PHASESFig 6

No

. of

mo

lecu

les

•Pipeline analysis reveals that there are XX molecules in various stages of pipeline (focusedon Discovery, Pre-clinical, Phase I, II, III and Marketed candidates)

•The Pre-clinical stage commanded the pipeline analysis with XX molecules, followed by phase IIwith around XX molecules.

•PR, REG & APP ---- Pre-Registered, Registered & Approved

Discovery Pre-clinical Phase I Phase II Phase III PR, REG & APP

Marketed

No

. of

mo

lecu

les

T2D PIPELINE BY LEADING PLAYERS

Fig 7N

o. o

f m

ole

cule

s

• GSK is leading with X molecules in T2D followed by Merck & Ember with X molecules each

• Companies such as Poxel and Eli Lilly are holding X molecules each

• Amgen and Connexios are holding X molecules each

No

. of

mo

lecu

les

GLOBAL T2D DRUG MARKET BY THERAPEUTIC SEGMENTATION

Small molecules

Large molecules

Monoclonal antibodies

Recombinant Proteins

Stem cell therapy

RNA based therapy

Fig 8

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The T2D pipeline is commanded by pharmacological drugs, accounting for XX molecules. Large molecules

accounting for XX molecules followed by Monoclonal antibodies, Recombinant proteins, Stem cell therapy, RNA

base therapy, Gene therapy and others.

RNA based therapy

Gene therapy

Others

TYPE 2 DIABETESTYPE 2 DIABETESSMALL MOLECULESSMALL MOLECULESSMALL MOLECULESSMALL MOLECULES

SMALL MOLECULES MOLECULE PHASE MOA COMPANY SUMMARY

Anagliptin MarketedDPP-4

inhibitorKowa Research

Institute

Anagliptin is an orally active DPP-4 inhibitor, for thetreatment of type-2 diabetes. In April 2013, the companylaunched oral anagliptin in Japan for the treatment of type-2diabetes mellitus.

XX XX XX XX XX

XX XX XX XX XX

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XX XX XX XX XX

XX XX XX XX XX

TYPE 2 DIABETESTYPE 2 DIABETESLARGE MOLECULESLARGE MOLECULESLARGE MOLECULESLARGE MOLECULES

LARGE MOLECULES MOLECULE PHASE MOA COMPANY SUMMARY

Lixisenatide Marketed GLP-1 agonist SanofiLixisenatide is a glucagon like peptide 1 receptor agonist, forthe treatment of T2D. In October 2014, the company launchedthe drug Lyxumia (brand name) for T2D in Brazil.

XX XX XX XX XX

XX XX XX XX XX

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XX XX XX XX XX

XX XX XX XX XX

TYPE 2 DIABETESTYPE 2 DIABETESMONOCLONAL ANTIBODIESMONOCLONAL ANTIBODIESMONOCLONAL ANTIBODIESMONOCLONAL ANTIBODIES

MONOCLONAL ANTIBODIES

MOLECULE PHASE MOA COMPANY SUMMARY

Gevokizumab Phase IIInterleukin 1

beta inhibitorXOMA

Corporation

Gevokizumab, a monoclonal antibody administeredsubcutaneously for the treatment of type 1 and 2 diabetes. Asper clinical trial data, the drug completed phase II trial inpatients with type 1 and 2 diabetes.

XX XX XX XX XX

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XX XX XX XX XX

XX XX XX XX XX

TYPE 2 DIABETESTYPE 2 DIABETESSTEM CELL BASED THERAPYSTEM CELL BASED THERAPYSTEM CELL BASED THERAPYSTEM CELL BASED THERAPY

STEM CELL THERAPYMOLECULE PHASE MOA COMPANY SUMMARY

XX XX XX XX XX

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XX XX XX XX XX

XX XX XX XX XX

TYPE 2 DIABETESTYPE 2 DIABETESRNA BASED THERPYRNA BASED THERPYRNA BASED THERPYRNA BASED THERPY

RNA-BASED THERAPY

MOLECULE PHASE MOA COMPANY SUMMARY

XX XX XX XX XX

XX XX XX XX XX

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XX XX XX XX XX

TYPE 2 DIABETESTYPE 2 DIABETESGENE THERAPYGENE THERAPYGENE THERAPYGENE THERAPY

GENE THERAPY

MOLECULE PHASE MOA COMPANY SUMMARY

XX XX XX XX XX

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TYPE 2 DIABETESTYPE 2 DIABETESRECOMBINANT FUSION PROTEINRECOMBINANT FUSION PROTEINRECOMBINANT FUSION PROTEINRECOMBINANT FUSION PROTEIN

RECOMBINANT PROTEINS THERAPY

MOLECULE PHASE MOA COMPANY SUMMARY

XX XX XX XX XX

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XX XX XX XX XX

XX XX XX XX XX

T2D KEY PLAYERS - HEADQUARTERS

Fig 11

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COMPANY-ADDEX THERAPEUTICS

OVERVIEWHEADQUARTERS

Addex therapeutics is a biotechnological company founded in the year 2002and is headquartered in Switzerland. The company mainly focus ondiscovering and developing orally available small molecule drugs calledallosteric modulators, to treat broad range of diseases. The company usesits proprietary discovery platform to address receptors and other proteinsthat have been undruggable for conventional drug discovery methodsincluding GPCR, receptor tyrosine kinases and cytokine receptors. Manytargets have been widely recognized as attractive for modulation ofimportant diseases with unmet medical needs.

SWITZERLAND

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PIPELINEPIPELINE

Discovery Pre-Clinical Phase I Phase II Phase III Marketed

ADX-91886

important diseases with unmet medical needs.

XX

XX

XX

XX

XX

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