Lipaglyn TM Discovery, Development & Preclinical Studies

1. LipaglynTM Discovery, Development & Preclinical Studies

2. LIPAGLYNTM A novel, first-in-class NCE with beneficial effects on both lipid and glycemic parameters

3. A milestone in Indian history……

4. Lipaglyn™ is world’s first approved dual PPAR-α/γ agonist

5. LipaglynTM is completely different in structure and attributes from TZDs/Glitazones All glitazones have Thiazolidinione ring and caused edema and weight gain Saroglitazar does not have TZD ring and did not cause edema & weight gain Studies have indicated that thiazolidinedione ring may generate reactive metabolites after metabolism, which may cause toxicity

6. 28675_84 LipaglynTM binds more strongly to PPAR- α than Fenofibrate LipaglynTM Fenofibrate LipaglynTM: Stronger binding with PPAR-α as a result of 4 H-bonding sites as against only 2 H-bonding sites in the case of Fenofibrate

7. LipaglynTM: ‘A million times’ more potent in activating PPAR- than Fenofibrate In vitro PPAR Agonistic activity in HepG2 Cells

8. 4_84 LipaglynTM demonstrates thousand fold higher selectivity for PPAR-α over PPAR-γ Saroglitazar is a potent and predominantly PPARα agonist with optimal  PPARγ agonistic activity In vitro PPAR Agonistic activity in HepG2 Cells

9. Spectrum of PPAR activity of various agents : Each PPAR agonist is unique *Illustrative chart Adapted from - http://www.theheart.org/documents/sitestructure/en/content/programs/1228135/1228135.html

10. PPAR agonists are not a class of drugs, each drug has unique properties* Dr. Steven Nissen at ADA Meeting, 2012 “The binding of different ligands to Nuclear Receptors induces different conformational changes. Each drug has a characteristic co-factor binding pattern.”

11. Saroglitazar is different from Other Glitazars Muraglitazar Farglitazar Tesaglitazar SAROGLITAZAR Ragaglitazar Aleglitazar Sodelglitazar Imiglitazar

12. Saroglitazar is different from TZDs Rosiglitazone Troglitazone Pioiglitazone Ciglitazone SAROGLITAZAR Balaglitazone Isoglitazone Rivoglitazone

13. Saroglitazar is different from fibrates Fenofibrate Gemfibrozil Saroglitazar Benzafibrate Clofibrate

14. 34819_85 LipaglynTM was extensively profiled for efficacy in various preclinical models of dyslipidemia • Models of diabetes & insulin resistance • db/db mice • Zucker fa/fa rats • Nondiabetic animal models • Swiss albino mice • High fat-high cholesterol diet-fed Golden Syrian hamsters • High cholesterol diet-fed Sprague Dawley rats • Nonhuman Primate (Marmosets)

15. LipaglynTM reduces serum triglycerides in a dose-dependent manner in various animal models db/db mice Zucker fa/fa rats Diabetic animal models Swiss albino mice mice High fat-High Cholesterol Diet Fed Hamsters Nonhuman Primates (Marmosets) Non-diabetic animal Models • Non-diabetic Abimal Models • Up to 76 % TG reduction in Swiss Albino Mice • Up to 90 % TG reduction in High fat-High cholesterol-fed Hamsters • Up to 61% reduction in serum triglycerides in Primates Diabetic & Insulin Resistant Models • Up to 55% TG reduction in db/db mice • Up to 86 % TG reduction in Zuckerfa/farats

16. LipaglynTM improved lipid clearance and reduced serum cholesterol levels Improved Lipid Clearance in Swiss Albino Mice High Cholesterol Diet Fed Sprague Dawley rats Potential to reduce Post-prandial hyperlipidemia • Up to 68% improvement in lipid clearance in Swiss Albino mice • Up to 77 % reduction in serum cholesterol in high-cholesterol diet-fed Sprague Dawley rats • Potential for Post prandial hyperlipidemia

17. 43011_85 LipaglynTM also has anti-diabetic effects in various animal models • Effects in db/db mice • Effects in Zuckerfa/fa rats • Glucose Clamp study in Zuckerfa/fa rats for Insulin sensitizing effects

18. LipaglynTM showed anti-hyperglycemic and insulin sensitizing effects in diabetic & insulin resistant animals (db/db mice and Zucker fa/fa rats) Effect on serum glucose Effect on AUCglucose in OGTT Effect on Serum Insulin db/db mice • db/db mice : Animal Model for Type 2 Diabetes Mellitus & Insulin Resistance • Up to 65 % reduction in serum glucose; Up to 59 % reduction in AUCGlu in OGTT; 91 % reduction in serum insulin at 1mg/kg Hyperinsulinemic Euglycemic Clamp Study Effect on Glucose Infusion rate Effect on AUCglucose in OGTT Effect on Serum Insulin & FFA Zucker fa/fa Rats • Zucker fatty fa/fa Rats: Animal model for Insulin-resistance • 85% reduction in serum insulin; Up to 52 % reduction in AUCGlu in OGTT • Improvement in Glucose infusion rate in hyperinsulinemiceuglycemic clamp study

19. 3_85 7_89 Preclinical Evidence of Safety • All Preclinical toxicity studies conducted in GLP (OECD) certified lab (Global quality standard) • Our research center (ZRC) also has AAALAC, NABL & CAP accreditation • Data acceptable globally OECD - The Organization for Economic Co-operation and Development AAALAC – Association for Assessment and Accreditation of Laboratory Animal Care International NABL – National Accreditation Board for Testing and Calibration Laboratories CAP – College of American Pathologists

20. Safety pharmacology studies show that LipaglynTM does not affect CNS, CVS, Respiratory and GI functions

21. Extensive toxicity studies including 2 yr carcinogenicity study have shown no safety concerns

22. 61443_85 Overall Conclusions of Preclinical Safety & Toxicity Studies • LipaglynTM is safe and well tolerated • No hepatotoxicity, myotoxicity, nephrotoxicity or cardiotoxicityat doses equivalent to or higher than efficacy doses • Non-genotoxic & Non-teratogenic • Passed 2-year carcinogenicity study (confirmed by a mechanistic study using non-human primates employing molecular biomarkers).

23. 8_85 LipaglynTM: Pre-clinical ADME Profile

24. Preclinical Data of LipaglynTM was Presented at 72nd ADA Meeting, June 2012, Philadelphia, USA

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