IQ4I Research & Consultancy Pvt. Ltd. Type II Diabetes Mellitus Pipeline Analysis



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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 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 Confidential SMALL MOLECULES Pipeline Competitive Analysis LARGE MOLECULE Pipeline Competitive Analysis MONOCLONAL ABs Pipeline Competitive Analysis STEMCELL THERAPY Pipeline Competitive 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

REPORT DESCRIPTION Type 2 Diabetes (T2D) Pipeline Analysis gives comprehensive insight on the various drugs being developed for the treatment of T2D. The report covers all the drugs being developed in various phases (Discovery, Preclinical, Clinical & Marketing). The pipeline focuses on novel pharmacologic drugs & regenerative medicines covering small molecules, monoclonal antibodies, stem cell therapies, Gene therapies, Recombinant proteins and RNA-based therapeutics, but excludes symptom relief drugs, generic combinations. The report also covers some of the hot targets in research for T2D treatments and disease progression biomarkers. This report enables Pharmaceutical /Biotech companies, Academic institutes, Individual researchers, Investors, Medical technology companies, Service providers and other associated stake holders to identify and analyze the available licensing/collaborative commercial opportunities in the Type 2 Diabetes (T2D) Drug market. The report also provide strategic insights on medicines that are likely to have an impact on T2D treatment space and potentially alter standards of care in T2D in the foreseeable future. Current therapies are focused on the treatment of hyperglycemia than on pancreatic Beta cell dysfunction and they 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 increase in cardiovascular risk. Hence, it provides a tremendous opportunity for upcoming therapies specific to T2D such as MAbs, stem cell-based, gene therapies and RNA-based therapies. These modalities may provide beta-cell protection, regeneration, mass increase with additional benefits of weight loss, triglyceride lowering and kidney protection.

TYPE II DIABETES - INTRODUCTION Type 2 Diabetes Mellitus formerly known as noninsulin-dependent diabetes mellitus (NIDDM) and adult-onset disease is a metabolic disorder which is characterized by reduced insulin sensitivity, insulin resistance and pancreatic β-cell dysfunction Diabetes Facts Globally, around 371 million people are living with diabetes and type 2 diabetes accounts for90% of all diabetes cases. Currently, highest number of people with diabetes occurs in 40-59 years age group. As of March 2013, approximately 23 million children & adults were observed with T2D. Expenditure on diabetes in North American region was higher than other region. And by 2050, 1 in 3 American adults will have diabetes. In 2013, International Diabetes Federation (IDF) estimated 10 million people with diabetes in China, India, USA, Brazil & Russian Federation. People at major risk North America-34.2M South & Central America 23.4M Non Hispanic Whites= 7.6% Asian Americans = 9% Hispanics = 12.8% Non Hispanic Blocks = 13.2% American Indians/Alaska Natives = 15.9% Prevalence Europe 49.5 M Africa-13.5M Diabetes Affects Rural, 36% Middle East & North Africa 30.6 M South East Asia-63M Urba n, 64% Western Pacific- 118.8M

TYPE II DIABETES - CAUSES AND SYMPTOMS Causes Symptoms Overweight Obesity Genetic susceptibility Risk factors 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 Increased thirst & hunger Dry mouth Polyurination Unexplained weight loss Fatigue Blurred vision Headache Loss of consciousness Slow healing sores/cuts Decreased vision Impotency Frequent yeast infections Acanthosis nigricans Numbness & tingling of hands & feet

TYPE II DIABETES - DIAGNOSIS BLOOD TEST BLOOD CREATINI NE & URINE MICROALB UMIN DIAGNOSIS HEMOGLO BIN A1C LIPID TEST

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 Fig 1 Pakistan X MN Russia Federation X MN {MN: Million} USA X MN Mexico X MN Egypt X MN Japan X MN China X MN Brazil X MN India X MN Indonesia 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 MELLITUS Current therapies for T2DM are relatively effective in controlling hyperglycemia. Some examples include: Current Therapies Thiazolidinediones Sulfonylurea derivatives α-glucosidaseinhibitors Glucagon-like peptide-1 receptor agonists Dipeptidyl peptidase-4 inhibitors Long-acting DPP-4 inhibitors Insulin secretagogues SGLT-1/2 inhibitors Insulin sensitizers Pyruvate dehydrogenase inhibitors Fibroblast growth factors 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 readmissionrate (%) Medicaid Patient 3.5% 3.3% Privately insured patient 2.1% 1.7% Uninsured patient 4.6% 4.1%

TYPE 2 DIABETES MARKET DATA

T2D MARKET: FORECASTING MODEL Fig 2 Historical Data and trends of T2D Market Pipeline Evolution Evolution Market Share T2D Costs of Burden Company Developments Hospitalization Pattern Epidemiology Pattern Applications Download Pattern Readmission Regulatory Landscape Pattern Geographical Usage Factors Influencing Market Growth Market Drivers High unmet need Increasing incidence of diabetes and diabetes related disorders Increasing aged population Alteration in lifestyle Market Penetration Innovative drug discovery platforms Market Opportunities Acquisitions/collaborations of companies and research institutes Demand for novel drugs to increase revenue of pharma industry Market Restraints High cost of drugs and 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. Market Trends and Forecasting 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 2018.

T2D : MARKET DYNAMICS Fig 3 DRIVERS High unmet need Increasing incidence of diabetes and diabetes related disorders Increasing aged population & obese Alteration in lifestyle OPPORTUNITIES Global T2D Market RESTRAINTS High cost of drugs and innovative therapies (stem cell and gene therapies) Risk of pancreatitis, pancreatic & thyroid cancer associated with incretin based therapies THREATS Acquisitions/collaborations of diagnosis companies and research institutes Demand for T2D drugs in emerging markets Innovative drug delivery platforms Patent expiration of small molecules Entry of basal insulin biosimilars pose significant threat Confidential

T2D - MARKET SIZING Fig 4 Fig 5 Global T2D Drugs Market Global T2D Drugs Market by Region Market size ($Billion) Market size ($Billion) 2014 2021 2014 2015 2016 2017 2018 2019 2020 2021 Year NA EU AP ROW Region 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. Confidential

TYPE 2 DIABETES PIPELINE ANALYSIS

T2D PIPELINE BY PHASES Fig 6 No. of molecules Discovery Pre-clinical Phase I Phase II Phase III PR, REG & APP Marketed Pipeline analysis reveals that there are XX molecules in various stages of pipeline (focused on Discovery, Pre-clinical, Phase I, II, III and Marketed candidates) The Pre-clinical stage commanded the pipeline analysis with XX molecules, followed by phase II with around XX molecules. PR, REG& APP---- Pre-Registered, Registered & Approved

T2D PIPELINE BY LEADING PLAYERS Fig 7 No. of molecules 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

GLOBAL T2D DRUG MARKET BY THERAPEUTIC SEGMENTATION Fig 8 Small molecules Large molecules Monoclonal antibodies Recombinant Proteins Stem cell therapy RNA based therapy Gene therapy Others 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. Confidential

TYPE 2 DIABETES SMALL MOLECULES

SMALLMOLECULES MOLECULE PHASE MOA COMPANY SUMMARY Anagliptin Marketed DPP-4 inhibitor KowaResearch Institute Anagliptin is an orally active DPP-4 inhibitor, for the treatment of type-2 diabetes. In April 2013, the company launched oral anagliptin in Japan for the treatment of type-2 diabetes mellitus. Confidential

TYPE 2 DIABETES LARGE MOLECULES

LARGE MOLECULES MOLECULE PHASE MOA COMPANY SUMMARY Lixisenatide Marketed GLP-1 agonist Sanofi Lixisenatide is a glucagon like peptide 1 receptor agonist, for the treatment of T2D. In October 2014, the company launched the drug Lyxumia(brand name) for T2D in Brazil. Confidential

TYPE 2 DIABETES MONOCLONAL ANTIBODIES

MONOCLONAL ANTIBODIES MOLECULE PHASE MOA COMPANY SUMMARY Gevokizumab Phase II Interleukin 1 beta inhibitor XOMA Corporation Gevokizumab, a monoclonal antibody administered subcutaneously for the treatment of type 1 and 2 diabetes. As per clinical trial data, the drug completed phase II trial in patientswithtype 1and 2diabetes. Confidential

TYPE 2 DIABETES STEM CELL BASED THERAPY

STEM CELL THERAPY MOLECULE PHASE MOA COMPANY SUMMARY Confidential

TYPE 2 DIABETES RNA BASED THERPY

RNA-BASED THERAPY MOLECULE PHASE MOA COMPANY SUMMARY Confidential

TYPE 2 DIABETES GENE THERAPY

GENE THERAPY MOLECULE PHASE MOA COMPANY SUMMARY Confidential

TYPE 2 DIABETES RECOMBINANT FUSION PROTEIN

RECOMBINANT PROTEINS THERAPY MOLECULE PHASE MOA COMPANY SUMMARY Confidential

T2D KEY PLAYERS - HEADQUARTERS Fig 11 Confidential

COMPANY-ADDEXTHERAPEUTICS HEADQUARTERS SWITZERLAND OVERVIEW Addex therapeutics is a biotechnological company founded in the year 2002 and is headquartered in Switzerland. The company mainly focus on discovering and developing orally available small molecule drugs called allosteric modulators, to treat broad range of diseases. The company uses its proprietary discovery platform to address receptors and other proteins that have been undruggable for conventional drug discovery methods including GPCR, receptor tyrosine kinases and cytokine receptors. Many targets have been widely recognized as attractive for modulation of important diseases with unmet medical needs. PIPELINE Discovery Pre-Clinical Phase I Phase II Phase III Marketed XX ADX-91886 XX XX XX XX Confidential

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