EX-99.1 2 a09-3124_1ex99d1.htm EX-99.1

Exhibit 99.1

 

1 Metabasis Investor Meeting January 13, 2009 January 13, 2009 JPM Meeting 2 Agenda • Introductory Remarks • Dr. Garber’s Presentation – 4-week Phase 2A trial on MB07803 – Q&A • R&D Pipeline Review – Company Q&A

 


2 January 13, 2009 JPM Meeting 3 Forward-Looking Statements This presentation includes forward-looking statements that are based on our management's current beliefs and assumptions and on information available to our management on the date of the presentation. This presentation was given during the week of January 13, 2009 and is only valid as of that date. Forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. Please see the sections entitled "Risk Factors" and "Forward-Looking Statements" in Metabasis’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2008 for a more detailed description of these risks and uncertainties as well as additional information regarding forward-looking statements. January 13, 2009 JPM Meeting 4 Agenda • Introductory Remarks • Dr. Garber’s Presentation – 4-week Phase 2A trial on MB07803 – Q&A • R&D Pipeline Review – Company Q&A

 


3 January 13, 2009 JPM Meeting 5 Company Overview • R&D Focus – Metabolic Diseases – Liver • Pipeline – 4 clinical stage compounds – Several advanced pre-clinical programs • Partnerships – HCV (Roche, Idenix, Merck) – Diabetes (Merck) January 13, 2009 JPM Meeting 6 Pipeline Overview PII PI Lead Opt Preclin Disc Roche Royalty Idenix Pharmaceuticals Royalty Merck & Co Royalty Merck & Co US Co-promotion Worldwide Worldwide Worldwide Worldwide Worldwide PARTNER/ COMMERCIAL RIGHTS Hepatitis C Unnamed #2 Hepatitis C Unnamed #2 Primary Liver Cancer MB07133 Diabetes MB07803 Hepatitis B Pradefovir Diabetes AMPK Project Diabetes Glucagon Antagonist Hyperlipidemia MB07811 Hepatitis C Unnamed #1 PIII Programs / Products

 


4 January 13, 2009 JPM Meeting 7 Pipeline Overview PII PI Lead Opt Preclin Disc Roche Royalty Idenix Pharmaceuticals Royalty Merck & Co Royalty Merck & Co US Co-promotion Worldwide Worldwide Worldwide Worldwide Worldwide PARTNER/ COMMERCIAL RIGHTS Hepatitis C Unnamed #2 Hepatitis C Unnamed #2 Primary Liver Cancer MB07133 Diabetes MB07803 Hepatitis B Pradefovir Diabetes AMPK Project Diabetes Glucagon Antagonist Hyperlipidemia MB07811 Hepatitis C Unnamed #1 PIII Programs / Products January 13, 2009 JPM Meeting 8 Near Term Goals PII PI Lead Opt Preclin Disc Hepatitis C Unnamed #2 Hepatitis C Unnamed #2 Liver Cancer MB07133 Diabetes MB07803 Hepatitis B Pradefovir Diabetes AMPK Project Diabetes Glucagon Antag Hyperlipidemia MB07811 Hepatitis C Unnamed #1 Programs / Products • Initiate 12-week P2 trial on MB07811 for hyperlipidemia • Extend runway well beyond end of 7811-201 trial – Reduce operating expenses – Achieve near term milestones (Merck, Roche) – Secure new partnerships • Define path forward for MB07803 and partner – Regulatory review – Marketing assessment

 


5 January 13, 2009 JPM Meeting 9 MB07811: Opportunity • Patient Population and Medical Need – Large number of patients with high LDL and/or high TG • 350 million in 7 major pharmaceutical markets – Significant fraction of these patients are at high risk • Most fail to meet target lipid goals • Statins – Reduce cardiovascular disease mortality by 28%A – Significant number of patients can not take statins • TR Agonists – Expected to combine with statins • may further reduce cardiovascular disease mortality – Expected to produce a unique lipid lowering profile • Reduce LDL • Reduce TGs • Reduce Lp(a) • Reduce hepatic steatosis AHerbert PR et al. JAMA 278, 313 (1997) January 13, 2009 JPM Meeting 10 Thyroid Receptor Agonists • Efficacy (Liver) (TRß) – Reduce total cholesterol – Reduce atherogenic lipoproteins LDL-C, Lp(a) – Reduce triglycerides • Safety (non-Hepatic) – Cardiovascular (TR) • heart rate, cardiac hypertrophy, contraction, conductance – TSH suppression – Muscle wasting (TR) – Bone loss Two TR subtypes (TR Two TR subtypes (TR and TR and TRß)

 


6 January 13, 2009 JPM Meeting 11 Erion, M.D. et al. Proc. Natl. Acad. Sci. USA 104, 15490 (2007) Liver-Targeted TRß Agonist • Demonstrated Liver Targeting – Drug distribution – Gene expression • Liver • Heart • Pituitary • Kidney • Thyroid • Muscle • Kidney – Functional activity • Lipid Lowering • Cardiac Function • Biomarkers (muscle, pituitary, fat) Heart Liver Intestinal Contents High Low 14C Tissue Distribution (24 h) lymph(c) thyroid testes fat bladder prostate spleen pancreas stomach lymph(m) small int. large int. liver adrenal kidneys thymus heart lungs marrow muscle eyes brain pituitary skin blood plasma bone % of Dose 0.0 0.5 1.0 1.5 2.0 2.5 Liver 14C QWBA (4 h) January 13, 2009 JPM Meeting 12 MB07811: Improved Therapeutic Index Days 0 10 20 30 40 50 Plasma Cholesterol (mg/dL) 50 100 150 200 250 300 350 Vehicle MB07811 (10 mg/kg) * * * * * * * Lipid Lowering (DIO Mice) Safety (SD Rats) TSH 0 5 10 15 20 25 0.0 0.2 0.4 0.6 0.8 1.0 1.2 * * TSH (ng/mL) TSHß mRNA (rel units) Heart Rate nmole/kg/day (p.o) 101 102 103 104 105 % Change from Vehicle -20 -10 0 10 20 30 40 KB-141 MB07811 T3 SD Rats Vehicle KB-141, (0.5 mg/kg) MB07811, (4 mg/kg) Cholesterol Hepatic Steatosis

 


7 January 13, 2009 JPM Meeting 13 Design: Single-center (domiciled), randomized, double-blind, PBO-controlled, ascending multi-dose study Objectives: Safety (emphasis: hepatic, cardiac), tolerability, PK Doses: PBO, 0.25, 1, 2.5, 5, 10, 20 and 40 mg Sample size: n = 8/cohort (3:1 randomization MB07811:PBO) Subjects: Healthy volunteers, LDL-C >100 mg/dL MB07811-102: Multi-dose Study January 13, 2009 JPM Meeting 14 MB07811-102: Lipid Lower Activity No apparent change HDL-Cholesterol Dose related decrease of 28 to 56% Lp(a) Dose related decrease of 9 to 40% Apo B Dose related decrease of greater than 30% Triglycerides Dose related decrease ranging from 15 to 41% LDL-Cholesterol Comments Change

 


8 January 13, 2009 JPM Meeting 15 MB07811-102: Safety Summary • Fifty-four (96%) subjects completed the study – One discontinued due to AE • No SAEs • % AEs in MB07811-treated subjects similar to PBO-treated subjects • No apparent cardiac effects – No difference in heart rate – No difference in blood pressure – No clinically significant Holter findings • Dose-related mean shifts in thyroid hormones – No thyroid hormone associated AEs nor signs, symptoms or changes in vitals, ECGs or Holter findings • Dose-related mean shifts in liver function tests – One MB07811 subject (40 mg) ALT and AST > 3 x ULN; resolved without interruption of MB07811 treatment January 13, 2009 JPM Meeting 16 Metabasis’ Diabetes Programs PII PI Lead Opt Preclin Disc Roche Royalty Idenix Pharmaceuticals Royalty Merck & Co Royalty Merck & Co US Co-promotion Worldwide Worldwide Worldwide Worldwide Worldwide PARTNER/ COMMERCIAL RIGHTS Hepatitis C Unnamed #2 Hepatitis C Unnamed #2 Primary Liver Cancer MB07133 Diabetes MB07803 Hepatitis B Pradefovir Diabetes AMPK Project Diabetes Glucagon Antagonist Hyperlipidemia MB07811 Hepatitis C Unnamed #1 PIII Programs / Products

 


9 January 13, 2009 JPM Meeting 17 Diabetes Strategy: Reduce Hepatic Glucose Production [Glucose] ( . ) Metabolism Pancreas Liver Muscle Liver Fat Production 1. FBPase Inhibitors 2. Glucagon Antagonists 3. AMPK Activators (Merck) January 13, 2009 JPM Meeting 18 Target Rationale Maggs et al. Ann. Internal Med. 128, 176-185 (1998) Liver Glucose Production – Increased in type 2 diabetes – Correlates with rise in fasting plasma glucose levels – Inhibited by metformin • Primary mechanism of action Metabasis Targets – Fructose-1,6-bisphosphatase • Rate-limiting enzyme in gluconeogenesis (GNG) pathway • GNG increased in T2DMs – Glucagon receptor • Glucagon elevated in T2DMs – AMP-Activated Protein Kinase • Possible metformin target

 


10 January 13, 2009 JPM Meeting 19 Fructose-1,6-bisphosphatase Inhibitors: Pre-Clinical Studies 25 Vehicle CS-917 EGP, mg/kg/min. 0 5 10 15 20 -46% -70% +58% Gluconeogenesis Glycogenolysis Total Day 0 2 4 6 8 10 12 14 . Blood glucose (mg/dL) -150 -100 -50 0 50 100 Control, n=8 ~30 mg/kg/day, n=8 ~100 mg/kg/day, n=8 * * * * * * (Baseline BG ~ 280 mg/dL) Inhibits Gluconeogenesis Lowers Blood Glucose Erion, M.D. et al. Proc. Natl. Acad. Sci. USA 102, 7970-7975 (2005) van Poelje, P.D. et al. Diabetes 55, 1747-1754 (2006) January 13, 2009 JPM Meeting 20 Fructose-1,6-bisphosphatase Inhibitors • First Generation (CS-917) - Significant glucose lowering in Phase 2A studies (Daiichi Sankyo) - Safe and well tolerated A few cases of asymptomatic lactacemia Increased GI intolerability at higher doses - Two cases of lactic acidosis when combined with metformin - Failed to meet primary efficacy endpoint in P2B - Significant reduction in FPG in patients with baseline FPG >180 mg/dL - Daiichi Sankyo terminated program in early 2008 • Second Generation (MB07803) – Designed to address PK short-comings of CS-917 Formation of long-lived N-acetylated metabolite Limited oral bioavailability Drug variability Duration

 


11 January 13, 2009 JPM Meeting 21 MB07803: Clinical Results • Phase 1 Trials – No N-acetylated metabolite formed – Good oral bioavailability and suitably low drug variability – Well tolerated • Phase 2A Trial (Dr. Garber) – Demonstrated initial proof-of-concept • 7803-105 Trial – Identified a tablet formulation that enables increased exposure • 7803-113 Trial – Safety and PK of MB07803 at higher drug exposure • Tablets • BID dosing – 14 day in-patient trial in T2DMs • Cohort #1: 50 mg and 200 mg BID • Cohort #2: 400 mg BID – Study completed at end of 2008 • Topline results expected Q1, 2009 January 13, 2009 JPM Meeting 22 FBPase Inhibitors – Opportunity • Patients contraindicated for metformin therapy – Renal impairment • Other potential target patient populations – Patients that fail to tolerate metformin – Non-metformin using patients with advanced type 2 diabetes failing to achieve adequate glycemic control Source : ADA, CDC National Diabetes Fact Sheet, L.E.K. Interviews and Analysis 1,754 1,486 353 289 375 4,257 2nd 1,616 1,744 366 300 389 4,415 3rd 1,466 454 209 172 222 2,523 1st Line of Therapy 759 1,041 196 161 208 2,365 5th 709 971 183 150 194 2,207 4th 6,303 5,696 1,309 1,072 1,388 15,768 Total 40.0% 36.1% 8.3% 6.8% 8.8% 100% % of Total Assumptions Units Number of Treated Type 2 Patients by Line Therapy 000s Number of Patients by Sub-segment Contraindicated not on Metformin 000s GI Intolerant on Metformin 000s GI Intolerant not on Metformin 000s Other Not on Metformin 000s Tolerant Patients on Metformin 000s

 


12 January 13, 2009 JPM Meeting 23 Current Status & Plans • Next Steps – Discuss regulatory path forward with FDA – Complete a market assessment • Establish a corporate partnership – POC in T2DM – Regulatory Path – Marketing assessment January 13, 2009 JPM Meeting 24 Glucagon Antagonist Program Rationale – Increased glucagon in T2DM • Increased liver glucose production – DPPIV inhibitors • Reduce glucagon levels – Antagonists • Reduce glucose production Challenging Drug Target – Finding drug-like compounds • Potency • Oral bioavailability • Metabolism

 


13 January 13, 2009 JPM Meeting 25 Discovered Novel Compound Series MB09975N IC50 = 5.8 nM [MB09975N] nM 0.001 0.01 0.1 1 10 100 1000 125I-glucagon, cpm 0 2000 4000 6000 8000 10000 12000 14000 16000 18000 20000 Human Receptor Binding • High affinity • High specificity • Potent glucose lowering • Good oral bioavailability • High metabolic stability van Poelje et al., 2008 ADA (Poster #043-2007) January 13, 2009 JPM Meeting 26 Glucagon Antagonist Program: Status & Plans Day 0 1 2 3 4 5 6 7 Blood glucose, mg/dL (3 pm) 100 200 300 400 500 600 Vehicle Single dose M B09975N , day 7 MB09975N , 30 mg/kg, BID Lean (vehicle) * * * * p < 0.001 all interactions; RMANOVA *p < 0.05 v. all others; ANOVA-Tukey Kramer • Advanced leads identified – Sustained glucose lowering in animal models • Fasting, postprandial – Good PK profile across species • High oral bioavailability • Low metabolism – Good safety profile • Partnering (on-going) – Compound recommendation for development expected in H1 09

 


14 January 13, 2009 JPM Meeting 27 AMP Activated Protein Kinase (AMPK) • AMPK Activators – Reduce glucose production by liver – Increase glucose metabolism in muscle • Merck Collaboration – 4th year – 2008/9 Goal: development candidate January 13, 2009 JPM Meeting 28 Non-Core Product Pipeline PII PI Lead Opt Preclin Disc Roche Royalty Idenix Pharmaceuticals Royalty Merck & Co Royalty Merck & Co US Co-promotion Worldwide Worldwide Worldwide Worldwide Worldwide PARTNER/ COMMERCIAL RIGHTS Hepatitis C Unnamed #2 Hepatitis C Unnamed #2 Primary Liver Cancer MB07133 Diabetes MB07803 Hepatitis B Pradefovir Diabetes AMPK Project Diabetes Glucagon Antagonist Hyperlipidemia MB07811 Hepatitis C Unnamed #1 PIII Programs / Products

 


15 January 13, 2009 JPM Meeting 29 HepDirect Prodrug Technology Prodrug (inactive) Prodrug Drug Conversion Delivery Drug Elimination • Liver-Targeted Drug Delivery – Demonstrated pre-clinically – Indirect evidence in humans • Drug Candidates – Pradefovir (hepatitis B) – MB07133 (primary liver cancer) – MB07811 (hyperlipidemia) – Unnamed (HCV, pre-clinical) • Merck • Idenix • Roche January 13, 2009 JPM Meeting 30 Pradefovir (Hepatitis B) (targets a known anti-viral to the liver) 48 week Phase 2 Results Treatment Group 0 100 200 300 400 500 5 mg PDV 10 mg PDV 20 mg PDV 30 mg PDV 10 mg Hepsera 42 73 134 224 298 n=14 n=12 n=11 n=13 n=11 PMEA AUC 0-24hr (ng.h/mL ) PDV PDV PDV PDV Hepsera 298 -4.22 -3.39 -4.33 -5.02 -3.66 Similar Efficacy Reduced Exposure • Status – Phase 2 trial completed • Strong antiviral activity • Evidence for liver targeting – Product returned to Metabasis • Positive findings in 2-year carcinogenesis studies • HBV Market – Scientific review completed with favorable results – Partnering activity planned for 2009

 


16 January 13, 2009 JPM Meeting 31 MB07133 (Hepatocellular Carcinoma) (targets a proven anti-cancer agent to liver) Baseline Cycle 10 Ma et al. Ma et al. AACR. AACR. Poster #19 (2007) Poster #19 (2007) • Status – Phase 1/2 clinical trial in patients completed with promising results – Licensing discussions in progress January 13, 2009 JPM Meeting 32 Business Development - 2009 PII PI Lead Opt Preclin Disc Hepatitis C Unnamed #2 Hepatitis C Unnamed #2 Liver Cancer MB07133 Diabetes MB07803 Hepatitis B Pradefovir Diabetes AMPK Project Diabetes Glucagon Antag Hyperlipidemia MB07811 Hepatitis C Unnamed #1 Programs / Products • Glucagon Antagonist – Bolster discussions through advancement of lead • MB07133 • Pradefovir • MB07803 – Regulatory review – Marketing assessment

 


17 January 13, 2009 JPM Meeting 33 Near Term Goals PII PI Lead Opt Preclin Disc Hepatitis C Unnamed #2 Hepatitis C Unnamed #2 Liver Cancer MB07133 Diabetes MB07803 Hepatitis B Pradefovir Diabetes AMPK Project Diabetes Glucagon Antag Hyperlipidemia MB07811 Hepatitis C Unnamed #1 Programs / Products • Initiate 12-week P2 trial on MB07811 for hyperlipidemia • Extend runway well beyond end of 7811-201 trial • Define path forward for MB07803 and partner Metabasis Investor Meeting January 13, 2009

 


 

1 1 MB07803-202 MB07803-202 Phase 2a Efficacy, Safety and Tolerability Study of MB07803, a Second-Generation Fructose-1,6- Bisphosphatase Inhibitor, in Patients with Type 2 Diabetes Mellitus (T2DM) Alan Garber, MD, PhD; Barry Gumbiner, MD; Sharon Watling, PharmD; Jeff Jensen, MS; Theresa Stern, PhD; Mark Erion, PhD; and Howard Foyt, MD, PhD for the MB07803-202 Investigators The World Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy) November 1, 2008, Barcelona, Spain 2 MB07803-202 MB07803 Rationale Glycolysis Gluconeogenesis (GNG) Fructose-1,6- bisphosphatase (FBPase) Phosphoenolpyruvate Carboxykinase Pyruvate Carboxylase Phosphoenolpyruvate Pyruvate Kinase Glucose Glucose-6-Phosphate Glucose-6-Phosphatase Hexokinase / Glucokinase Fructose-6-Phosphate Fructose-1,6-bisphosphate Phosphofructokinase Oxaloacetate Pyruvate Alanine Lactate Aspartate Glycerol T2DM Defects .Substrate flux & (-) Glucokinase & (-) PFK & (+) FBPase up-regulated .GNG .Endogenous glucose production Fasting Postprandial hyperglycemia hyperglycemia

 


2 3 MB07803-202 • Potent, selective inhibitors of FBPase discovered using structure-based drug design • Novel prodrug strategy delivers inhibitor to liver • Pre-clinical studies demonstrate: – Robust efficacy across T2DM models – Good safety in chronic toxicology studies MB07803 (prodrug) MB07803 MB07729 (active metabolite FBPaseI) Esterase Phosphoramidase MB07803 Rationale (cont.) Proc. Natl. Acad. Sci. USA 102, 7970-7975 (2005) Diabetes 55, 1747-1754 (2006) 4 MB07803-202 Study Design * 10 mg arm dropped after 60 subjects enrolled * (n = 105 enrolled) • Objectives: assess the safety, tolerability, and efficacy of MB07803 administered for 28 days in patients with T2DM • Design: multi-center, double-blind, randomized, PBO-controlled • Subjects: – non-insulin treated T2DM – age 18 - 70 yo – BMI 18.5 - 40 kg/m2 – FPG 140 - 270 mg/dL

 


3 5 MB07803-202 Baseline Demographics Demographic Category Placebo MB07803 10 mg MB07803 50 mg MB07803 100 mg MB07803 200 mg Total MB07803-202 Total Subjects (n) 23 13 23 23 23 105 Gender (n) Males Females 18 5 6 7 16 7 13 10 9 14 62 43 Age (y) * 56.4 (7.7) 53.1 (9.6) 54.8 (9.6) 52.3 (9.3) 53.3 (8.5) 54.1 (8.8) Race (n) Cauc/Black/Other 20 / 1 / 2 8 / 3 / 2 19 / 3 / 1 18 / 5 / 0 20 / 2 / 1 85 / 14 / 6 Ethnicity (n) Hispanic or Latino 11 8 12 8 12 51 BMI (kg/m2 ) * 31.7 (4.5) 31.0 (4.7) 29.4 (4.3) 29.9 (5.4) 30.7 (5.5) 30.5 (4.9) HbA1c (%) * 8.1 (1.0) 7.9 (0.9) 8.1 (1.2) 8.2 (1.1) 8.6 (1.2) 8.2 (1.1) FPG (mg/dL) * 185.0 (41.7) 177.7 (46.9) 174.8 (39.0) 187.6 (38.0) 206.4 (50.7) 187.1 (43.8) Duration T2DM (y) * 6.3 (5.5) 4.7 (4.6) 6.6 (4.1) 6.8 (6.6) 6.1 (5.9) 6.2 (5.4) * mean (SD) 6 MB07803-202 Subject Disposition • Randomized: 105 subjects • Completers: 99 subjects • Discontinuations: – hyperglycemia (FPG > 300 mg/dL on consecutive visits; n = 3) • 10 mg (n = 2) • 200 mg (n = 1) – SAE • acute MI (100 mg) – reported Day 2 – onset of cardiac symptoms ~2 days prior to randomization (Day -2) • aortic valve stenosis; carotid artery stenosis; CAD; MI (200 mg) – reported Day 15 – macular rash • PBO (n = 1)

 


4 7 MB07803-202 Efficacy Results - Day 28 vs. Baseline .FPG (mg/dL) All Subjects .FPG 206.4 (50.7) 187.6 (38.0) 174.8 (39.0) 177.7 (46.9) 185.0 (41.7) Baseline FPG * (- 52.6, - 5.1) - 28.9 ** (-37.7, -3.8) -20.7 23 200 mg (-23.5, 23.4) 0.0 (-8.4, 24.7) 8.1 23 100 mg (-26.4, 20.6) -2.9 (-11.4, 22.0) 5.3 23 50 mg (-28.3, 26.9) -0.7 (-14.7, 29.5) 7.4 13 10 mg ----- ----- (-8.4, 24.7) 8.2 23 PBO 95% CI LSM 95% CI LSM N PBO-adjusted .FPG Linear regression of individual datapoints suggests MB07803 efficacious dose in this patient population = 200 - 400 mg ** p = 0.0177 vs. PBO * mean (SD) 8 MB07803-202 Efficacy Results - Day 28 vs. Baseline .FPG (mg/dL) in Subjects with Baseline FPG = 180 mg/dL .FPG 230.6 (39.0) 212.3 (20.7) 218.4 (19.3) 215.5 (40.3) 216.3 (30.0) Baseline FPG * (- 87.0, - 12.5) - 49.7 ** (-59.1, -10.0) -34.6 16 200 mg (-52.4, 23.4) -14.5 (-25.3, 26.6) 0.6 14 100 mg (-61.7, 26.1) -17.8 (-36.6, 31.4) -2.6 8 50 mg (-45.1, 51.1) 3.0 (-21.2, 57.5) 18.2 6 10 mg ----- ----- (-12.6, 43.0) 15.2 12 PBO 95% CI LSM 95% CI LSM N PBO-adjusted .FPG ** p = 0.0099 vs. PBO source: table D3.1.3 * mean (SD)

 


5 9 MB07803-202 Meal Tolerance Test Glycemia (mg/dL) 200 mg Group 10 MB07803-202 Treatment-emergent Adverse Events Placebo (N=23) 10 mg (N=13) 50 mg (N=23) 100 mg (N=23) 200 mg (N=23) All MB07803 Doses (N=82) Patients with at least one AE 9 (39.1) 3 (23.1) 7 (30.4) 11 (47.8) 6 (26.1) 27 (32.9) System Organ Class/ Preferred Term n (%) n (%) n (%) n (%) n (%) n (%) Hypoglycemia 0 (0.0) 0 ( 0.0) 0 (0.0) 0 (0.0) 1 (4.3) 1 (1.2) Cardiac 1 (4.3) 0 ( 0.0) 0 (0.0) 1 (4.3) 1 (4.3) 2 (2.4) Incidence = 5% Gastrointestinal 2 (8.7) 1 (7.7) 1 (4.3) 5 ( 21.7) 1 (4.3) 8 (9.8) Musculoskeletal/connective tissue 3 (13.0) 1 (7.7) 3 (13.0) 2 ( 8.7) 1 (4.3) 7 (8.5) Nervous system 1 (4.3) 2 (15.4) 2 ( 8.7) 2 ( 8.7) 1 (4.3) 7 (8.5) Infections and infestations 1 (4.3) 0 (0.0) 1 (4.3) 2 ( 8.7) 3 (13.0) 6 (7.3) Investigations (e.g. phlebotomy) 2 (8.7) 0 (0.0) 1 (4.3) 2 ( 8.7) 0 (0.0) 3 (3.7) • Low overall incidence of AEs • GI intolerance low

 


6 11 MB07803-202 Plasma Lactate Summary • No AEs of lactic acidosis • No AEs of hyperlacticemia Placebo (N = 23) 10 mg (N = 13) 50 mg (N = 23) 100 mg (N = 23) 200 mg (N = 23) Fasting Plasma Lactate (mmol/L) [Mean (SD)] * Baseline 1.40 (0.58) 1.35 (0.43) 1.33 (0.45) 1.50 (0.57) 1.49 (0.59) . Mean [Day 28 - Baseline] ** 0.15 (0.60) -0.01 (0.46) -0.07 (0.46) -0.10 (0.49) 0.20 (0.44) Frequency of Fasting Plasma Lactate > 4.5 mmol/L (n) Randomized – prior to drug 1 0 1 0 0 Randomized – on drug 0 0 0 0 1 Two (2) consecutive *** 0 0 0 0 0 * fasting plasma lactate reference range: 0.5 – 2.2 mmol/L ** N = 22, 11, 23, 22, 21 for PBO – 200 mg, respectively *** pre-specified discontinuation criterion 12 MB07803-202 Summary • Treatment of T2DM patients with MB07803 for 28 days: – is safe and well-tolerated – results in a clinically meaningful decrease in FPG at 200 mg Conclusions • The results of MB07803-202 demonstrate: – once daily administration of the novel FBPase inhibitor, MB07803, to T2DM results in clinically meaningful reduction in FPG – clinically meaningful improvement of glycemia beyond that attainable by prandial regulation alone – further exploration of MB07803 glucose-lowering potential at higher doses is warranted

 


7 13 MB07803-202 MB07803-202 Investigators James Rhyne, Statesville, N.C. Franklin Zieve, Richmond, VA George Raad, Charlotte, N.C. Richard Weinstein, Walnut Creek, CA John Pullman, Butte, MT Gilbert Weiner, Miami Gardens, FL David Morin, Bristol, TN Sanjay Vora, Marion, OH Thomas Moretto, Indianapolis, IN Philip Toth, Indianapolis, IN Andrew Lewin, Los Angeles, CA Roberto Segura, Chicago, IL Yekaterina Khronusova, Las Vegas, NV Sherwyn Schwartz, San Antonio, TX Donald Hurley, Charleston, S.C. Jaime Sandoval, Corpus Christi, TX Alan Garber, Houston, TX Eli Roth, Cincinnati, OH Ernesto Fuentes, Miami, FL