Madrigal Pharmaceuticals, Inc. · NASDAQ:MDGL
Madrigal Pharmaceuticals — Merger or Acquisition (May 2016)
29 slides from Madrigal Pharmaceuticals's merger presentation, May 2016
Slide 1: The New Madrigal Pharmaceuticals
The New Madrigal Pharmaceuticals NASDAQ: SNTA | May 2016 1
Slide 2: Forward-Looking Statements
Forward-Looking Statements Any statements made in this press release relating to future financial or business performance, conditions, plans, prospects, trends, or strategies and other financial and business matters, including without limitation, whether and when our recently announced merger with M
Slide 3: Additional Information about the Merger and Where to Find It
Additional Information about the Merger and Where to Find It This presentation does not constitute an offer to sell or the solicitation of an offer to buy any securities or a solicitation of any vote or approval. A definitive proxy statement and a proxy card will be filed with the SEC and will be ma
Slide 4: Transaction Terms
Transaction Terms • Synta to acquire all outstanding shares of Madrigal in All Stock Transaction exchange for approximately 253.9 million newly issued shares of Synta common stock • Synta shareholders expected to own 36.0% of the combined Name and Ownership company and Madrigal shareholders expected
Slide 5: The New Combined Company: Investment Highlights
The New Combined Company: Investment Highlights MGL-3196: First-in-Class • Phase 2-ready liver-directed thyroid hormone THR-ß Agonist receptor-ß agonist (THR-ß); efficacy and safety profile validated by preclinical and clinical data Large & Underserved Markets in • Initial indications are NASH and f
Slide 6: Synta-Madrigal Leadership
Synta-Madrigal Leadership • Combined company will be led by an experienced management team with multiple successful NDA/EMAs and marketed products – Paul Friedman, M.D. - Chairman and CEO • Former CEO of Incyte Pharmaceuticals; former President of DuPont Pharmaceuticals Research – Rebecca Taub, M.D.
Slide 7: MGL-3196: Building a Platform in Lipid and Liver Disorders
MGL-3196: Building a Platform in Lipid and Liver Disorders 7
Slide 8: Building a Platform in Lipid and Liver Disorders with MGL-3196
Building a Platform in Lipid and Liver Disorders with MGL- 3196, a First-in-Class Thyroid Hormone-β (THR-β) Agonist Lead compound, MGL-3196, a Phase 2-ready liver-directed thyroid hormone receptor-β First-in-Class (THR-β) agonist Approach • Once-daily oral dosing • Favorable safety and efficacy prof
Slide 9: Madrigal Pipeline
Madrigal Pipeline Compound/Target Disease State Pre-Clinical Phase 1 Phase 2 Phase 3 MGL-3196 NASH Thyroid Hormone Receptor-β (THR-β) Agonist FH MGL-3745 Thyroid Hormone – (Same as 3196) Receptor-β (THR-β) Agonist (Backup) • Thyroid analogue platform (MGL-3196, backup, new molecules) • Biliary disor
Slide 10: MGL-3196, a First-in-Class Liver-Directed THR-β Agonist
MGL-3196, a First-in-Class Liver-Directed THR- β Agonist • We believe MGL-3196 is the first bona fide THR-β selective molecule – Discovery of MGL-3196 and backups at Roche utilized a novel functional assay that went beyond what previous companies had done (simple receptor binding assay) – Earlier co
Slide 11: MGL-3196, a First-in-Class Liver-Directed THR-β Agonist
MGL-3196, a First-in-Class Liver-Directed THR- β Agonist MGL-3196’s demonstrated and potential properties: • Once daily oral dosing (Atherosclerosis 230 (2013) 373-380) • High liver uptake; low tissue penetration outside liver (preclinical studies) • Demonstrated and potential THR-β actions and bene
Slide 12: Differentiated NASH Opportunity
Differentiated NASH Opportunity Large & • WW NASH market estimated at $35bn-$40bn Growing • While epidemiology data varies, ~2-3% of the US population is thought to have NASH, and expected to grow given the high rate of growth of obesity and diabetes Unserved • No FDA approved treatment options Mark
Slide 13: Why MGL-3196 for NASH?
Why MGL-3196 for NASH? We believe that MGL-3196 will treat the underlying disease in NASH patients • MGL-3196 has pleiotropic effects characteristic of an “ideal” NASH drug – Potentially fixes components of the metabolic syndrome, treats insulin sensitivity, dyslipidemia, and underlying fatty liver
Slide 14: THR-β Benefits Across the Spectrum of Early to Advanced NASH
THR-β Benefits Across the Spectrum of Early to Advanced NASH Evidence from human and animal data from Madrigal and multiple published studies support pleiotropic actions of THR-ß NASH Normal Liver Fatty Liver Cirrhosis inflammation and fibrosis METABOLIC BENEFITS ANTI-INFLAMMATORY REDUCED NASH Effec
Slide 15: MGL-3196: Preclinical Data Support NASH and Lipid Indications
MGL-3196: Preclinical Data Support NASH and Lipid Indications • Improved safety profile relative to T3 (thyroid hormone) and other thyroid agonists • Reduced markers of NASH in diabetic and obese animals including: – Reduction in fatty liver – Improved liver enzyme levels – Decreased inflammation an
Slide 16: MGL-3196: Improved Safety Profile Relative to T3
MGL-3196: Improved Safety Profile Relative to T3 24d study in 40 week old diet-induced obese (DIO) mice on High Fat Diet (HFD) for 38 weeks Cholesterol T3 Bone Mineral Density 300.0 0.06 Cholesterol (mg/dl±s.d.) Bone Density (g/cm*cm) 250.0 0.05 ** *** *** 200.0 *** 0.04 Thyroid hormone 150.0 *** 0.
Slide 17: MGL-3196: Data Supports Improvement in Liver Health
MGL-3196: Data Supports Improvement in Liver Health Upper panels: 24d study in 17 wk old DIO mice (po, qd) on high fat diet (HFD) 13 wks; lower panels: 24d study in 40 wk old DIO mice on HFD 35 wks Liver Size Liver Triglycerides 5 70 Insulin Tolerance Test Liver % Body Weight 120 Triglycerides mg/g
Slide 18: Reduction of Key NASH, Fibrosis Pathway Genes at Human Comparable Drug Levels
MGL-3196: Reduction of Key NASH, Fibrosis Pathway Genes at Human Comparable Drug Levels 25 week study in DIO, lean control mice and HFD mice treated with 0.1 to 3 mg/kg MGL-3196 or Rosiglitazone (3mg/kg) MGL-3196 (mg/kg) HFD mouse model Inflammation HFD Lean 0.1 0.3 1 3 Rosi MCP-1/CCL2 • Up-regulati
Slide 19: MGL-3196: Long-term Dosing in Humans is Enabled
MGL-3196: Long-term Dosing in Humans is Enabled Completed: • Single Ascending Dose (SAD) study • Multiple Ascending Dose (MAD) study – Six dose cohorts, 36 total HV dosed daily with MGL-3196 (5, 20, 50, 80, 100, or 200 mg) and 12 with placebo for 14 days • Healthy volunteers with slightly elevated L
Slide 20: Robust LDL and Triglyceride Lowering in 14-Day Multiple Dose Phase 1 Study
MGL-3196: Robust LDL and Triglyceride Lowering in 14 Day Multiple Dose Phase 1 Study Change in Lipids After 14 Days 20 10 %Change From Baseline MGL-3196, 0 Placebo Subtracted Chol LDL-C ApoB Non-HDL-C TG -10 * * * -20 ** ** *** ** *** ** ** ** *** *** -30 *** *** *** -40 -50 “ *** p<0.001 ** p<0.01
Slide 21: Strong Positioning in NASH Landscape
Strong Positioning in NASH Landscape NAS Fibrosis Liver NASH Insulin CV Compound Phase LDL TGs Side Effects Score Score Lipids Prevention Sensitivity Risk CV Well- MGL-3196 1 ✔ ✓ ✔ ✔ ✔ Benefit tolerated ✔Benefit ✓Small benefit Decrease Green = Good • Pleiotropic and cardio-beneficial actions po
Slide 22: Proposed Phase 2 Proof-of-Concept NASH Protocol
Proposed Phase 2 Proof-of-Concept NASH Protocol Study Study Details Drug MGL-3196 Inclusion/Exclusion 80, 120 mg qd • NASH on liver biopsy • Include diabetics, statin therapy Design Blinded 1:1:1 Comparator/Arms • Placebo vs. MGL-3196 (2 doses) Stage Ph2 Primary Endpoint • Reduction of liver fat (MR
Slide 23: Unmet Needs in FH, a Severe Genetic Dyslipidemia
Unmet Needs in FH, a Severe Genetic Dyslipidemia • HeFH and HoFH caused primarily by inactivating mutations in LDL Severe Debilitating receptor Dyslipidemia • Early onset cardiovascular disease, HoFH < age 20 Prevalence • 1/200-1/500 HeFH; 1/250,000-1/1,000,000 HoFH • Higher frequency in certain gen
Slide 24: Current Challenges in Treatment of FH
Current Challenges in Treatment of FH HoFH • Most patients still not reaching LDL-C goal HoFH LDL • Newer agents, Lomitapide (Juxtapid, MTPi) and Lipid Lowering Therapy decrease Mipomersen (Kynamro, anti-ApoB) may have safety Conventional issues Statins Up to 28% • Both carry FDA label warning*, hep
Slide 25: MGL-3196: Unique and Complementary Lipid Lowering Profile
MGL-3196: Unique and Complementary Lipid Lowering Profile Cholesterol Breakdown Elimination MGL-3196 both LDL receptor dependent and independent ApoB cholesterol lowering Lp(a) • Thyroid pathway clinically validated and differentiated in FH – MGL-3196 lowers LDL in concert with statins in clinical,
Slide 26: Proposed Phase 2 HeFH Clinical Trial Protocol
Proposed Phase 2 HeFH Clinical Trial Protocol Study Study Details Drug MGL-3196 Inclusion/Exclusion 80,120 mg qd • FH on low, high dose statins, ezetimibe • Subgroup may be on PCSK9ab (allowable “n” under discussion Design 1:1:1 Comparator/Arms Stage Ph2 • Placebo controlled, blinded # Patients 100
Slide 27: Proposed Phase 2a HoFH Clinical Trial Protocol
Proposed Phase 2a HoFH Clinical Trial Protocol Study Study Details Drug MGL-3196 Inclusion/Exclusion 80,120 mg qd • HoFH on standard care, may include PCSK9ab, statins, ezetimibe Design Open label Comparator/Arms Stage Ph2 • Patients is his own control • MGL-3196 may be titrated # Patients 6-8 Prima
Slide 28: Potential Near and Long-term Value Drivers
Potential Near and Long-term Value Drivers 2015 2016 2017 • Completed MGL- Clinical trial initiations: Potential Data Readouts: 3196 long-term • Ph2 in NASH: • Ph2 interim safety & efficacy toxicology studies 6-month liver biopsy data for HeFH trial extension study (late 16/early 17) • MGL-3196 dose
Slide 29: Thank you
Thank you NASDAQ: SNTA | May 2016 29
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