Lipocine Inc. · NASDAQ:LPCN
Lipocine — Investor Presentation (January 2019)
67 slides from Lipocine's investor presentation, Jan 28, 2019
Slide 1: Corporate Presentation
Enabling oral drug delivery to improve patient compliance January 28, 2019 Corporate Presentation Exhibit 99.1
Slide 2: Forward-Looking Statements
Forward - Looking Statements This presentation contains forward - looking statements about Lipocine Inc. (the “Company”). These forward - looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward - looking statement s re
Slide 3: Unique Specialty Pharmaceutical Company
Men's Health Oral Testosterone Replacement Therapy (“TRT”) Oral Androgen Therapy for Fatty Liver Disease (“NAFLD”/ “NASH”) Women's Health Oral Therapy for Prevention of Preterm Birth (“PTB”) Proprietary Drug Delivery Platform Significant Unmet Need In Both Therapeutic Areas Unique Specialty Pharmace
Slide 4: Late-Stage Pipeline
Late - Stage Pipeline 4 Oral Product Candidates Targeting Significant Opportunities PRODUCT (Indication) PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NDA MEN’S HEALTH TLANDO™ (Oral Testosterone Replacement Therapy, TRT) ABPM Study Ongoing LPCN 1111 (Next Gen. Oral TRT) Phase 2 Completed LPCN 1144 (Oral Treat
Slide 5: Targeted for Testosterone Replacement Therapy
5 Targeted for Testosterone Replacement Therapy
Slide 6: TRT Market is Growing
2018 2017 2016 2014 2015 350 375 400 425 450 475 500 525 550 575 600 625 650 675 Sep 14 Nov 14 Jan 15 Mar 15 May 15 Jul 15 Sep 15 Nov 15 Jan 16 Mar 16 May 16 Jul 16 Sep 16 Nov 16 Jan 17 Mar 17 May 17 Jul 17 Sept 17 Nov 17 Jan 18 Mar 18 May 18 Jul 18 Sep 18 Nov 19 Monthly TRx (000s) FDA Label Guidanc
Slide 7: Issues with Current Non-oral TRT Options
Issues with Current Non - oral TRT Options • Black Box Warning – Secondary exposure to testosterone – Pulmonary oil micro embolism (POME) and anaphylaxis shock • Inconvenient application or painful injection • Poor persistence reflects need for oral – Average days on therapy is 100 days • More than
Slide 8: TLANDO: Path Forward for Resubmission
TLANDO™: Path Forward for Resubmission Confirmed Next Steps in Bring TLANDO to Patients Deficiencies and Plan for Resolution Determine extent, if any, of ex vivo conversion of TU to T Obtain definitive evidence pre - approval via ambulatory blood pressure monitoring study to exclude whether TLANDO c
Slide 9: TLANDO: Potential First Oral Option
TLANDO™: Potential First Oral Option Profile Demonstrated Clinically with Target Label Regimen ▪ Met primary endpoint - 80% response rate in “worst - case analysis” vs. FDA requirement of 75% ▪ Met key secondary endpoint - No eligible subjects with T levels >2500 ng/ dL ▪ Other secondary endpoints g
Slide 10: Targeted for Non-Alcoholic Steatohepatitis (NASH)
10 Targeted for Non - Alcoholic Steatohepatitis (NASH) A silent killer that affects 30 million Americans 1 Global market estimated to be ~$35 billion 1 1. CNBC; published December 30, 2018
Slide 11: LPCN 1144: Well Positioned for Success
LPCN 1144: Well Positioned for Success Unique Mechanism of Action with Compelling Clinical Signal ▪ Targeting Full Spectrum of NASH Pathogenesis + Additional Health Benefits - Testosterone deficiency in men is prevalent across the full spectrum of NAFLD - LPCN 1144 results suggest therapy has potent
Slide 12: NAFLD Clinical Progression
Non - Alcoholic Fatty Liver Disease (NAFLD) Clinical Progression 12 LFTs: Liver function test, especially Alaninine amino transferase (ALT) and Aspartame amino transferase (AST) NASH: Non - alcoholic Steatohepatitis, TG: Triglyceride Fatty liver is a reversible condition wherein large vacuoles of tr
Slide 13: Clinical Relationship Between Testosterone and NAFLD
Clinical Relationship Between Testosterone and NAFLD Across the Full Histological Spectrum Hepatic Steatosis NASH Cirrhosis “ Men with low testosterone are at high risk for NAFLD .” 1 Free T ( pg /mL) “ Levels of free T decreased significantly with the increased incidence of lobular inflammation, he
Slide 14: Proposed Mechanism of Action
Proposed Mechanism of Action Androgen Action via Androgen Receptor (“AR”) in Males* 14 Testosterone increases muscle protein synthesis*** * Navarro et al., Obesity 2015 ** Shen and Shi, Int J Endocrinol 2015 ***Brodsky et al., J Clin Endo Met 1996 Normal level and signaling of androgens prevent hepa
Slide 15: LPCN 1144: Targeting Full Spectrum of NASH Pathogenesis
Accumulation of Fat in Liver Cell Damage/ Steatosis Inflammation/ Steatohepatitis Fibrosis Cirrhosis Homeostasis Modifier Anti - Inflammatory Fibrosis Mediator / Regeneration LPCN 1144: Targeting Full Spectrum Of NASH Pathogenesis Plus Collateral Health Benefits ▪ Reduction of elevated ALT levels ge
Slide 16: T Deficiency Exacerbates Liver Disease Symptoms
T Deficiency Exacerbates Liver Disease Symptoms T Therapy Demonstrated Histological Improvement in Multiple Models Animal Model Castrated NAFLD Rat 1 Castrated Pig 2 Post T Therapy ▪ Hepatic steatosis ▪ Hepatic apoptosis ▪ Vesicular inflammation ▪ Hepatic lipids ▪ Liver injury ▪ Hepatocell
Slide 17: T Therapy Effects in Liver Regeneration
T Therapy Effects in Liver Regeneration Liver Mass Restoration in T Treated Hepatectomized Rat Model* ▪ 90% Hepatectomized rat groups 17 Fig 1. Group 1: 24 hr post hepatectomy. (I) massive steatosis, ( ch ) rare chromatin, organelle depletion = cell damage Fig 2. Group 2: 24 hr post hepatectomy. ( d
Slide 18: LPCN 1144: Liver Fat Imaging Study
LPCN 1144: Liver Fat Imaging Study (“LFS”) Study Design and Liver Fat Baselines 18 ▪ LFS is an open - label, multi - center single - arm 16 - week study (N=36) with LPCN 1144 in hypogonadal males LF = liver fat
Slide 19: LFS Interim Results: Liver Fat Change
LPCN 1144: LFS Interim Study Results Absolute and Relative Liver Fat % Change Post 8 Week Treatment 19 * N=7 available for MRI - PDFF scan for the interim analysis (~8 week) - 7.6% -10% -8% -6% -4% -2% 0% BL ≥ 10%* % Liver Fat CBL ( ± SEM) Mean Absolute Liver Fat % Change - 38.4% -50% -40% -30% -20%
Slide 20: LFS Interim Results: Responder Rates
20 LPCN 1144: LFS Interim Study Results Compelling Liver Fat Reduction Response Post 8 Week Treatment* * Clinically meaningful relationship of MRI - PDFF % reduction with histological response in NASH (Patel et al., Ther Adv Gastroenterol 2016) ** N=7 available for MRI - PDFF scan for the interim an
Slide 21: Absolute Liver Fat % Reduction
LPCN 1144: Absolute Liver Fat % Reduction Comparable/Better Liver Fat Reductions 21 BL PDFF % Criteria > 10% > 8% > 10% > 10% > 10% > 8% > 10% Mean 18.6% LPCN 1144 (LFS Study Interim Results); NGM282 (Harrison et al., NASH - TAG 2018); VK - 2809 (Press Release, Nov 2018); MGL - 3196 (Cor p ppt, Ever
Slide 22: Relative Liver Fat % Reduction
LPCN 1144: Relative Liver Fat % Reduction Comparable/Better Liver Fat Reductions 22 LPCN 1144 (LFS Study Interim Results); NGM282 (Harrison et al., NASH - TAG 2018); VK - 2809 (Press Release, Nov 2018); MGL - 3196 (Cor p ppt, Evercore ISI, Nov 2018); BMS986036 ( Sanyal et al., NASH - TAG 2018); NGM3
Slide 23: LFS Interim Results Summary
LPCN 1144: LFS Interim Results Summary Strong Liver Fat Reduction Signal in at Risk Hypogonadal Males ▪ Higher prevalence of NAFLD was observed in hypogonadal males relative to the general population, even after BMI stratification ▪ Substantial reductions of liver fat were achieved with LPCN 1144 th
Slide 24: Compelling Clinical Biomarker Data
- 64 - 35 - 19 - 9 - 21 12 - 33 -80 -60 -40 -20 0 20 LPCN 1144 (Wk 52) BL=1.6xULN‡ LPCN 1144 (Wk 52) BL=1.2xULN Obeticholic acid 25mg (Wk 72) BL=1.3xULN Cenicriviroc 150mg (Wk 52) BL=1.2xULN Selon/Simtu† 18mg/125mg (Wk 24) BL=1.2xULN Selon/Simtu† 6mg/125mg (Wk 24) BL=1.2xULN Aramchol 600mg (Wk 52) B
Slide 25: Elevated Biomarker Normalization
LPCN 1144: Elevated Biomarker Normalization Appreciable % of Patients Experienced Normalization of ALT, TG, LDL - C, and Liver Fat % * Data obtained from SOAR Trial; ALT, TG, and LDL - C normal range upper limit is 40 U/L, 200 mg/dL, and 160 mg/dL, respectively ** Data obtained from LFS; Liver fat %
Slide 26: Robust ALT Response
26 † Total N is for patients with ALT > 40 U/L at baseline (ALT normal range is ≤ 40 U/L) 43% 48% 0% 10% 20% 30% 40% 50% 60% N = 42* N = 71* LPCN 1144 (Wk 52) Vitamin E (Wk 120) % of ALT Responders at EOS * ALT Responders: Patients with ALT > 40 U/L at baseline, ending with ≤ 40 U/L and more than 30
Slide 27: Additional Health Benefits Observed
LPCN 1144: Additional Health Benefits Observed in Hypogonadal Subjects with Elevated ALT* SF - 36, Short Form - 36 (0 - 100); PDQ, Psychosexual Daily Questionnaire (0 - 7); * ALT > 40 U/L at Baseline in 52 week SOAR Trial (N=3 3) Mental Component Summary Mental Health Role Emotional Maintained Erect
Slide 28: Oral Testosterone for Treatment of NASH: Summary and Next Steps
LPCN 1144: Oral Testosterone for Treatment of NASH Summary and Next Steps ▪ Unique Mechanism Targeting Full Spectrum of NASH Pathogenesis + Additional Health Benefits - Testosterone deficiency in men is prevalent across the full spectrum of NAFLD - LPCN 1144 results suggest therapy has potential for
Slide 29: LPCN 1107
LIPOCIN= LPCN 1107
Slide 30: Prevention of Preterm Birth: US Market Landscape
LPCN 1107: Prevention of Preterm Birth (PTB) United States Market Landscape $1B Market Opportunity 3 December 31, 2017 HPC TRx 4 Makena ® 1 50% Off Guidance 2 30% Compounded 17 - HPC 20% 117% 1. Amag estimates Makena market share based on distributor dispensing data and all other market share based
Slide 31: LPCN 1107: First Oral PTB Candidate
LPCN 1107 - Oral HPC ▪ Potential for superior efficacy with Phase 3 target dose ▪ No patient discomfort upon administration ▪ Steady state achieved in 7 days ▪ Orphan drug designation – Major contribution to patient care ▪ Next steps: – Explore partnering opportunities LPCN 1107: First Oral PTB Cand
Slide 32: Upcoming Milestones
Upcoming Milestones 32 Near Term Value Drivers Event Expected Timing TLANDO™ ABPM study results 1Q 2019 LPCN 1144 Top - line POC clinical study results assessing liver fat changes via MRI - PDFF imaging in NAFLD/NASH patients Complete in - vivo model POC study in biopsy - confirmed NASH 1Q 2019 1Q 2
Slide 33: Key Financial Metrics
Key Financial Metrics 33 Stock Price, Market Cap, Cash Balance Ticker Symbol LPCN (Nasdaq Capital Market) Closing Stock Price (1/25/19) $1.59/share Market Capitalization (1/25/19) $37.5 million Cash Balance (9/30/18) $21.9 million* Bank Debt (9/30/18) $10.0 million * $5 M restricted
Slide 34: Lipocine Investment Highlights
MEN’S HEALTH • TLANDO™ : Potential first oral TRT option - Differentiated product targeting ~$2.0 billion established US TRT market • LPCN 1144 : Oral prodrug of bio - identical testosterone for NASH - Compelling clinical biomarker data in patients with typical comorbidities of NASH • LPCN 1111 : Ne
Slide 35: Appendix
LIPOCIN= Appendix
Slide 36: TLANDO
LIPOCIN= TLANDO™
Slide 37: Hypogonadism Affects Up to 6M American Men
Hypogonadism Affects Up to 20 M American Men 1,2 37 Significant Number of Untreated Hypogonadal Males ~6M Men with diagnosed hypogonadism 3 2.2M Men currently being treated 4 700,000 New naïve patients each year 5 1. US Census data. http://www.infoplease.com/us/census/data/demographic.html. 2. Mulli
Slide 38: TLANDO: Patient Market Research
TLANDO™: Patient Market Research Patient Enthusiasm Evident About Oral TRT 38 38 80% of interviewed TRT patients 30% 30% “Oral Form ” 30% “It’s not Gel”, “ Not Injection” “ Ease of Use” Likely or Highly Likely to Ask Physician to Prescribe TLANDO What Most Like About TLANDO? Other • TLANDO generates
Slide 39: TLANDO: Physician Market Research
TLANDO™: Physician Market Research Oral Agent is Most Important Attribute for Prescribers 39 QUESTION: What is the most important advantage of TLANDO? 66% 10% 8% 8% 5% 3% No/Low Risk of… Good Efficacy Easy Dosing/ Administration Easy/Less Titration Few Side Effects/ Well-tolerated N=212 (All Respond
Slide 40: TLANDO SOAR Study Blood Pressure Data
-4 -3 -2 -1 0 1 2 3 4 5 6 Mean SPB Change (mmHg) 13-001 TLANDO Week 3 (n=193) 13-001 TLANDO Week 7 (n=182) 13-001 TLANDO Week 13 (n=157) 13-001 TLANDO Week 26 (n=144) 13-001 TLANDO Week 39 (n=138) 13-001 TLANDO Week 52 (n=130) 13-001 TLANDO Overall (n=944) TLANDO™ SOAR Study Blood Pressure Data Syst
Slide 41: Oral TU: Dose-Systolic BP Relationship
Oral TU: Dose - Systolic BP Relationship Differences Between Single/Triplicate/ABPM Measurements Brand Mean Single SBP Mean Triplicate SBP Mean ABPM Daytime SBP Study / Dose D SBP from baseline Study / Dose D SBP from baseline Study / Dose D SBP from baseline JATENZO (High Dose) CLAR 09007 Day30 / P
Slide 42: TLANDO: Definitive Phlebotomy Study
TLANDO™: Definitive Phlebotomy Study Ex Vivo Conversion Assessment ▪ Study objective: ‒ To evaluate the extent, if any, of clinically meaningful ex vivo conversion of TU to T in serum blood collection tubes to confirm the reliability of TLANDO data results ▪ Study design: ‒ Open - label, single dose
Slide 43: LPCN 1144
LIPOCIN= LPCN 1144
Slide 44: Estimated NASH Prevalence in Hypogonadal Males
Estimated NASH Prevalence in Hypogonadal Males NAFLD is overrepresented in Hypogonadal Males 5.5M Male Hypogonadal NASH Patients 4 12.8M NAFLD 3 22M Hypogonadal 2 92M Males ages ≥ 30 yrs 1 44 1 US Census (2016) 2 Araujo AB et al., JCEM 2007 3 NAFLD prevalence of 58% estimated from Lipocine LFS study
Slide 45: Low T Association with NAFLD and Cirrhosis
Low T Association with NAFLD and Cirrhosis 45 x After adjusting for age, smoking, diabetes, exercise, BMI, TG and HDL, the lowest T quintile (110 – 317 ng/dL) have OR † of 5.12 (2.43 – 10.77) for NAFLD x Low T (<8.3 nmol/L; 239 ng/dL) remained a significant predictor of reduced survival in cirrhotic
Slide 46: Free T Association with NASH Progression
Free T Association with NASH Progression 46 Free T and NAFL/NASH Free T and Stages of NASH Fibrosis Patients with NASH show significantly lower free T than those with non - alcoholic fatty liver (NAFLD)* * Sumida et al, Gastroenterol Hepatol 2015 Free T Free T
Slide 47: LPCN 1144: Proposed Multidimensional Mechanism of Actions
LPCN 1144: Oral T Proposed Multidimensional Mechanism of Actions ▪ Homeostasis Modifier 1, 2 ‒ Alter lipid, cholesterol, and glucose metabolism ‒ Reduce visceral abdominal fat ‒ Modify activity of hepatic lipase, and skeletal muscle/ adipose lipoprotein lipase ▪ Anti - inflammatory 2 / Immuno - modu
Slide 48: LPCN 1144: Post-hoc Analysis Methods
LPCN 1144: Post - hoc Analysis Methods □ Analyses of LPCN 1144 therapy results were performed with multiple clinical studies involving hypogonadal male cohorts with baseline liver enzymes* and lipids** ▪ Placebo - controlled, randomized, double blind study ( M12 - 778 ) with four week treatment x An
Slide 49: LPCN 1144: Gastrointestinal Safety
LPCN 1144: Gastrointestinal Safety Gastrointestinal Disorders ≥ 1% in SOAR Trial 0 5 10 15 % Subjects LPCN 1144 Topical T 49
Slide 50: Significant Reduction in Liver Enzyme Levels
Significant Reduction in Liver Enzyme Levels • Placebo Controlled 4 Week Study (M12 - 778) - 47.4% - 47.3% - 11.5% - 21.0% - 11.0% - 6.6% - 15.8% - 16.7% -60% -50% -40% -30% -20% -10% 0% LPCN 1144 225mg BID LPCN 1144 300mg BID Placebo - adjusted Mean Change ( ± SEM ) ALT AST ALP GGT 50
Slide 51: Significant Reduction in ALT Levels
Significant Reduction in ALT Levels • Placebo Controlled 4 Week Study (M12 - 778) 2 - 11 - 11 -15 -10 -5 0 5 N = 6 9 9 Placebo LPCN 1144 225mg BID LPCN 1144 300mg BID ALT Mean Change from BL ( ± SEM), U/L p = 0.01 p = 0.02 51
Slide 52: Reductions of ALT in Patients at Risk of NAFLD
Reductions of ALT in Patients at Risk of NAFLD -25 -20 -15 -10 -5 0 0 13 26 39 52 Mean Change from BL ( ± SEM), U/L Study Period (Week) Sustained Reduction of Elevated ALT** Mean BL (U/L) 54.4 54.9 54.3 57.4 55.0 - 12 - 13 - 15 - 16 - 13 -25 -20 -15 -10 -5 0 OBS T2D HTN OBS & T2D MetS* ALT Mean Chan
Slide 53: Reductions of TG in Patients at Risk of NAFLD
• 52 Week SOAR Trial Reductions of TG in Patients at Risk of NAFLD -120 -100 -80 -60 -40 -20 0 0 13 26 39 52 TG Mean Change from BL ( ± SEM), mg/dL Study Period (Week) Sustained Reduction of Elevated TG** ** Patients + for TG > 200 mg/dL at BL (N=73); TG mean BL = 320 mg/dL In Patients † with NAFLD
Slide 54: Consistent Liver Function Improvement Across Studies
Consistent Liver Function Improvement Across Studies* - Effect Observed as Early as Week 3 - 17.4% - 10.3% - 5.1% - 9.6% - 18.8% - 13.2% - 10.1% - 18.5% -30% -25% -20% -15% -10% -5% 0% ALT AST ALP GGT Mean Change from BL ( ± SEM) SOAR (52 Week) 16-002 (3 Week) Mean BL (U/L) 53.6 55.6 32.0 32.6 74.0
Slide 55: LPCN 1144: Unique TG Reduction
• 52 Week SOAR Trial TG mean change post therapy in patients on oral T vs non - oral T therapy LPCN 1144: Unique TG Reduction 55 - 63.7 13.7 -80 -60 -40 -20 0 20 40 60 Mean BL = 320 mg/dL 323 mg/dL N = 73/210 34/104 LPCN 1144 Topical T Mean Change from Baseline (mg/ dL ) TG Mean Change after 52 Week
Slide 56: Oral T TG Reduction Comparison with Topical T
• 52 Week SOAR Trial LPCN 1144: Oral T TG Reduction Comparison with Topical T Across Various Comorbidities 56 -100 -80 -60 -40 -20 0 20 40 60 80 100 Overall Obesity Diabetes Hypertension OBS & Diab MeS* TG Mean Change from BL (mg/dL) Oral T Topical T * MeS : Metabolic syndrome (Obesity + Diabetes +
Slide 57: LPCN 1111 QD TLANDO
57 LPCN 1111 QD TLANDO
Slide 58: LPCN 1111: Next-Generation Oral TRT
LPCN 1111: Next - Generation Oral TRT ▪ Novel prodrug of testosterone for oral delivery ▪ Once - daily potential expected to sustain and improve market share of oral T franchise ▪ Once - daily feasibility established in Phase 2a and 2b clinical trials – Single - daily oral dose provides T levels in
Slide 59: LPCN 1107
LIPOCIN= LPCN 1107
Slide 60: High PTB Medical Costs
High PTB Medical Costs • 12% of all US pregnancies 1 (475 - 500K) result in PTB (< 37 weeks) - a leading cause of neonatal mortality and morbidity • First year medical costs for PTB infants are ~ 10x higher than for full term infants 2 • 28% of preterm births are to women with histories of early del
Slide 61: LPCN 1107: First Oral PTB Candidate
LPCN 1107: First Oral PTB Candidate 61 Characteristics of the Only Approved Product Options for PTB IM HPC, Makena ® : ▪ 20 - 25% patients below reported better efficacy HPC level threshold ▪ Total of 18 - 22 injections – Injection location: Upper - outer quadrant of the gluteus maximus – Weekly vis
Slide 62: LPCN 1107: Economic Impact
LPCN 1107: Economic Impact Potential Lower PTB Rate – US and Resulting Savings Assuming 4.3% lower PTB rate relative to Makena® ~6000 fewer annual PTBs‡ Estimated annual cost saving in ~$310M‡‡ 62 ‡: Assuming 100% of 140,000 eligible US population treated ‡‡: Assuming ~$51,600 medical costs/PTB
Slide 63: LPCN 1107: Commercial Outlook/Drivers
LPCN 1107: First Oral PTB Candidate First Oral HPC for Prevention of Recurrent PTB • Preferred route - of - administration is oral Strong Exclusivity Position • Orphan Drug Designation • Technology/IP protection Potential for Superior Efficacy • Fewer PTB babies with significant healthcare cost savi
Slide 64: LPCN 1107: HPC PK-PD Correlation
LPCN 1107: HPC PK - PD Correlation 64 HPC Concentration and PTB Rate with IM HPC, Makena 1 N=315 1. Caritis et al., Am J Obstet Gynecol. 2014 (N=315 subjects) 2. C trough C avg for IM Makena® • Lower % PTB rate can be expected with daily C avg 2 HPC levels ≥ 8.2 ng/mL 2 46.3% 27.0% 29.6% 31.3%
Slide 65: LPCN 1107: Dose Finding Study Design
LPCN 1107: Dose Finding Study Design • Open - label, four - period, four - treatment study • 12 healthy pregnant women - Ages 18 - 35 years; 16 - 18 weeks gestation • All subjects received all four treatments 65 PK Study: Oral LPCN 1107 vs IM HPC, Makena Treatment D 250mg Weekly Treatment C 800mg BI
Slide 66: LPCN 1107: Dose-Finding PK Study Results
LPCN 1107: Dose - Finding PK Study Results 1 66 Oral LPCN 1107 vs IM HPC, Makena 1. PK results obtained post 8 days of BID dosing for LPCN 1107 and post 5 weeks for weekly IM HPC, Makena Lower reported PTB rate threshold • HPC levels below 8.2 ng/mL: – Target LPCN 1107 Phase 3 dose was 0% vs 20% sub
Slide 67: LPCN 1107: Advancing to Phase 3 Readiness
LPCN 1107: Advancing to Phase 3 Readiness Phase 3 Special Protocol Assessment – Progress ▪ Concurrence with FDA to date: – Study Design Elements • Single Phase 3 study • Open label, active comparator, two parallel arms (1:1 randomization) • General inclusion and exclusion criteria and treatment dura