Agenda. LAF237 Oral DPP4 1 Inhibitor with Potential for Sustainable Diabetes Control LAF237

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1 Agenda Disease background and unmet need LAF237 background and New MoA data LAF237 review of new phase IIb/III data Study 239 Phase III monotherapy (52 week) vs. metformin Study 2329 Phase III monotherapy dose comparison Study 122 Phase IIb monotherapy dose-ranging Study 2311 Phase III add-on to insulin Timings and future clinical program 11 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani LAF237 Oral DPP4 1 Inhibitor with Potential for Sustainable Diabetes Control First in a highly attractive new class of compounds (incretin enhancer) Effective as monotherapy and in combination Effectively reduces HbA1c Good tolerability with no nausea and no significant effect on weight Mixed meal GLP-1 2 & GIP 3 active LAF237 DPP4 Has the potential for disease modification based on islet-cell effects GLP-1 & GIP actions 1 Dipeptidyl peptidase IV 2 Glucagon-like-peptide-1 3 Gastric inhibitory polypeptide 12 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 6

2 LAF237 Increases β-cell Responsiveness to Glucose in T2DM Insulin secretion (pmol/min/m 2 ) 7 5 LAF237 Day 1 LAF237 Day 28 ** ** 3 Versus placebo: *p <.5 **p < Glucose (mmol/l) * * Insulin secretion (pmol/min/m 2 ) Placebo Day 1 Placebo Day Glucose (mmol/l) Adapted from Mari A, et al. J. Clin Endocrinol Metab 9: , London Pharmaceutical Pipeline Event 25 / Ameet Nathwani LAF237 Improves and Sustains Islet Cell Function and Insulin Sensitivity over 1 year in T2DM Patients failing on stable metformin therapy β-cell function (insulin secretion) LAF237/metformin Placebo/metformin Insulin sensitivity pmol/l 3min/(mmol/L) * * * ml min -1 m * * Time (wk) Time (wk) *P <.5 vs. placebo; P <.1 vs. placebo Adapted from Ahren B, et al. Diabetes Care. 25;28: London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 7

3 Improvements in Islet Cell Function and Insulin Sensitivity With LAF237 Support Sustained Efficacy Seen Over 1 year HbA1c (%) 1. LAF237 5 mg/metformin 1 (n=42) Placebo/metformin 1 (n=29) p <.1 p < Week 1 Metformin dose mg/day Ahrén B. et Al., Diabetes Care London Pharmaceutical Pipeline Event 25 / Ameet Nathwani Agenda Disease background and unmet need LAF237 background and New MoA data LAF237 review of new phase IIb/III data Study 239 Phase III monotherapy (52 week) vs. metformin Study 2329 Phase III monotherapy dose comparison Study 122 Phase IIb monotherapy dose-ranging Study 2311 Phase III add-on to insulin Timings and future clinical program 16 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 8

4 Phase III Trial Design for Study 239 Long-term LAF237 Monotherapy Drug naïve patients with T2DM and HbA1c % Objective - HbA1c reduction at 12 months and maintenance to 2 years LAF237 1 mg TDD Placebo R n= 526 metformin 2 mg TDD n=254 2 weeks 52 weeks 52 week durability extension Study 239 data on file 17 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 52 week data 52 Week Data with Monotherapy Confirm Early and Sustained Reductions in HbA1c Mean HbA1c % * LAF237 1 mg (n=511) metformin 2 mg (n=249) Baseline 12 weeks 52 weeks 14 weeks Intent to treat: LAF237-1.% metformin -1.4% *p <.5 versus LAF237 Study 239 data on file per protocol population 18 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 9

5 Both LAF237 and Metformin Demonstrate Body Weight Neutrality Unlike SUs 1 and TZDs 2 Body weight (kg) 1 LAF237 1 mg (n=511) metformin 2 mg (n=249) 95 9 p = not significant Time (weeks of treatment) 1 2 Sulfonylureas Thiazolidinediones Study 239 data on file 19 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani LAF237 is Better Tolerated than Metformin AEs of special interest LAF237 1 mg (%) metformin 2 mg (%) (n=526) (n=254) Hypertension Edema Diarrhea Paresthesia.8 2. Nausea Myalgia Hypoglycemia.6.4 ECG 1 abnormalities Electrocardiogram Study 239 data on file 2 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 1

6 LAF237 Has a Superior GI Tolerability Profile to Metformin % Patients reporting events 5 P <.1 LAF237 1 mg (n=526) metformin 2 mg (n=254) Any GI events Abdominal pain Constipation Diarrhoea Dyspepsia Flatulence Nausea Vomiting Study 239 data on file 21 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani Phase III Trial Design for Study 2329 LAF237 Dose Comparison Drug naïve patients with T2DM and HbA1c 9-11% Primary objective: HbA1c reduction from baseline LAF237 5 mg and 1 mg total daily dose Pioglitazone used as a positive control for study validation LAF237 5 mg n= 17 Placebo R LAF237 1 mg n= 18 pioglitazone 3 mg n=55 2 weeks 12 weeks Study 2329 data on file 22 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 11

7 LAF237 Achieves Excellent, Dose-proportional Reductions in HbA1c Duration: 12 weeks LAF237 5 mg n=17 LAF237 1 mg pioglitazone 3 mg n=18 n=55 Mean HbA1c (%) Reduction % -1.6% -2 p < % p = NS Baseline HbA 1c Study 2329 data on file 23 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani LAF237 Demonstrates Excellent Responder Rates Duration: 12 weeks Responder rate (>.7% reduction in HbA1c) % LAF237 5 mg n=17 p <.4 8% 85% LAF237 1 mg n=18 p = NS pioglitazone 3 mg n=55 Study 2329 data on file 24 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 12

8 Phase IIb Trial Design for Study 122- LAF237 Dose-ranging Study Drug naïve patients with T2DM and HbA1c % Primary objective: HbA1c reduction from baseline LAF237 2 mg, 5 and 1 mg vs. placebo LAF237 1 mg n= 76 Placebo R LAF237 5 mg n= 72 LAF237 2 mg n= 71 placebo n=72 2 weeks 12 weeks Study 122 data on file 25 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani LAF237 Demonstrates Excellent, Doseproportional Reduction in HbA1c Duration: 12 weeks Mean HbA1c (%) Difference to Placebo LAF237 2 mg (n= 71) -.82* 26 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani LAF237 5 mg (n=72) -.95* *p <.1 versus placebo and baseline LAF237 1 mg (n=76) -1.2* Baseline HbA 1c Study 122 data on file 13

9 LAF237 Phase III Trial Design for Study 2311 Add-on to Insulin Patients with T2DM on insulin, HbA1c % Primary objective: To improve metabolic control as add-on to insulin LAF237 1 mg + Insulin (n=144) Insulin dose fixed R Placebo + Insulin (n=152) LAF237 5 mg + Insulin Run-in 4 weeks Double-blind treatment 24 weeks 28 week extension Study 2311 data on file 27 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani LAF237 Significantly Reduces HbA1c in T2DM Patients Requiring Insulin Duration: 24 weeks HbA 1c reduction (%) from baseline LAF237 1 mg + insulin Placebo + insulin p <.22 Baseline HbA 1c Study 2311 data on file 28 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 14

10 Reductions of HbA1c Achieved With Less Insulin Requirements and No Severe Hypoglycemic Events Duration: 24 weeks Change in insulin dose (IU) Grade 2 1 hypoglycemic events 6 1 LAF237 1 mg + insulin Placebo + insulin LAF237 1 mg + insulin Placebo + insulin 1 Blood glucose < 3.1 and symptoms suggestive of hypoglycemia and patient unable to initiate self treatment Study 2311 data on file 29 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani LAF237 New Phase IIb/III Data Summary New Phase IIb/III data confirms that LAF237 Reduces HbA1c levels in a dose-proportional, clinically meaningful manner in monotherapy and combination with insulin Sustains meaningful HbA1c reductions out to one year Has neutral body weight effects associated with HbA1c improvements Is very well tolerated Is associated with fewer severe hypoglycemic episodes when added to insulin Has the ideal profile as first drug of choice for combination treatment due to efficacy and safety profile, lack of drug-drug interactions and complementary mechanism of action 3 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 15

11 LAF237 Addresses Multiple Important Defects in T2DM Treatment Glucose influx from GI tract Impaired insulin action Inadequate glucagon suppression (α-cell dysfunction) Acute β-cell dysfunction Chronic β-cell decline α-glucosidase inhibitors TZDs Sulfonylureas Metformin Glinides LAF237 LAF237 LAF237 LAF237 LAF237 Decrease plasma glucose and slow disease progression Adapted from DeFronzo RA. Br J Diabetes Vasc Dis. 23;3(suppl 1):S24 S4 31 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani Agenda Disease background and unmet need LAF237 background and New MoA data LAF237 review of new phase IIb/III data Study 239 Phase III monotherapy (52 week) vs. metformin Study 2329 Phase III monotherapy dose comparison Study 122 Phase IIb monotherapy dose-ranging Study 2311 Phase III add-on to insulin Timings and future clinical program 32 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 16

12 Overview of Timing of Study Starts and Expected Data for LAF237 Islet Cell Protection Program Monotherapy vs. placebo & key comparators T2DM prevention Prevention and outcome data available: 29 and beyond Prevention of CVM 1 risk Free combination data with key products Filing in US 1 Cardiovascular/metabolic Durability prediabetes Durability Prevention Dis. modification Combo durability Long term CVM risk CVM risk Met durability 33 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani Summary and Conclusions Pancreatic islet dysfunction is the key determinant of the onset and progression of type 2 diabetes Clinical data confirms that LAF237 restore insulin sensitivity and normalises islet cell function long-term in patients with T2DM New phase IIb/III data shows that LAF237 has the ability to sustain reductions in HbA1c to clinically meaningful levels long-term in monotherapy and combination with insulin Further pivotal clinical data will be available in early 26 An extensive clinical trials program with LAF237 will define the role of islet cell protection in Delaying onset of T2DM (prevention) Slowing progression and maintaining control in T2DM (durability) Reducing CVM complications (disease modification) 34 London Pharmaceutical Pipeline Event 25 / Ameet Nathwani 17