Slide 1: Lipocine KOL Event: LPCN 2401 for Obesity Management
Lipocine KOL Event LPCN 2401 for Obesity Management October 16, 2024
Slide 2: Agenda
Agenda Introduction Dr. Mahesh Patel President and CEO Lipocine Obesity Treatment Landscape Dr. Frank Greenway Professor and Chief Medical Officer Pennington Biomedical Research Center LPCN 2401 P2 Results and Next Steps Dr. Ben Bruno VP of Clinical Development Lipocine Concluding Remarks Dr. Mahesh
Slide 3: Forward-Looking Statements
Forward-Looking Statements This presentation contains "forward-looking statements" that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and include statements that are not historical facts regarding our product development efforts, our strategi
Slide 4: Lipocine Pipeline and Approved Product
Lipocine Pipeline and Approved Product Development Candidate (Indication) Pre-Clinical Phase 1 Phase 2 Pivotal Status LPCN 1154 Anticipated NDA Filing Postpartum Depression Q4 2024 LPCN 2401 Initial P2 study Obesity Management completed LPCN 2203 P1 study completed Essential Tremor LPCN 2101 IND cle
Slide 5: LPCN 2401 Novel Oral Treatment for Obesity and Weight Management
LPCN 2401 Novel Oral Treatment for Obesity and Weight Management Proven potential to improve body composition - quality weight loss with quality fat loss Product Candidate Attributes • Proprietary androgen receptor agonist, testosterone ester(s), targeted for once-a-day treatment - “LPCN 2401” • And
Slide 6: LPCN 2401: Enabling Effective Oral Delivery
LPCN 2401: Enabling Effective Oral Delivery Testosterone Esters R Group R Undecanoate Tridecanoate Testosterone Ester Molecular Weight: 457-484 g/mol Aqueous Solubility: ≤ 70 ng/ml (calculated) clog P: ≥8.1 Giliyar et al. Drug Delivery Technology, Jan 2006, Vol 6 No.1 https://go.drugbank.com/ Lipoci
Slide 7: Speaker Introduction: Dr. Frank Greenway
Speaker Introduction: Dr. Frank Greenway Professor and Chief Medical Officer at Pennington Biomedical Research Center, a globally recognized institution for metabolic health research Dr. Greenway’s work encompasses a wide array of topics, including the development of pharmaceuticals for obesity Acad
Slide 8: Obesity Treatment Landscape
Obesity Treatment Landscape Dr. Frank Greenway, MD
Slide 9: Obesity Is a Global Public Health Crisis
Obesity Is a Global Public Health Crisis Obesity is a disease of excess and/or abnormal Complications of Obesity4 adipose tissue, not excess mass • Cardiometabolic risk correlates with adiposity Endocrine Cardiovascular • Diabetes mellitus • Sudden death • Cushing syndrome • Cardiomyopathy By 2030,
Slide 10: New Medications Are Transforming the Treatment of Obesity
New Medications Are Transforming the Treatment of Obesity • Highly potent AOMs and combination therapies (based on gut hormones) are achieving reductions in total body weight previously only possible with bariatric surgery but are limited by heterogeneity, tolerability, and other factors • Future tr
Slide 11: GLP-1 Agonists Have Been Associated With Excess Lean Mass Loss
GLP-1 Agonists Have Been Associated With Excess Lean Mass Loss • Up to 40% of total body weight loss realized with GLP-1 Figure 1 agonists is due to lean mass loss1,2 Dietary weight loss gives less than 25%. • With aging, there is an involuntary loss of muscle mass (~3–8% per decade) after age 303,4
Slide 12: GLP-1 Agonists Have Been Associated With Accelerated Bone Loss
GLP-1 Agonists Have Been Associated With Accelerated Bone Loss • Chronic use of GLP-1 agonists has been associated with reduced bone mass in the spine and hips, and decreased tibial cortical thickness relative to placebo2. May also increase reoperation for lumbar fusion 11. • Muscle loss and bone lo
Slide 13: Discontinuation of GLP-1 Agonists Is Associated With Rapid Weight Regain
Discontinuation of GLP-1 Agonists Is Associated With Rapid Weight Regain, Often in the Form of Visceral Fat • Approximately two-thirds of Americans stop GLP-1 therapy within 1 year of initiation1 • GI-related side effects are the most common reasons for discontinuation2 • Approximately two-thirds of
Slide 14: BMI and Total Body Weight Are Insufficient for Determining Obesity-Related Health Risk
BMI and Total Body Weight Are Insufficient for Determining Obesity-Related Health Risk or Treatment Response • Obesity is a disease of excess and abnormal adipose tissue, not excess mass • In 2023, the AMA adopted a policy discouraging the use of BMI alone in the diagnosis of obesity1 • Body Mass In
Slide 15: Obesity Is Overfat – Just Weight is Inaccurate
Obesity Is Overfat – Just Weight is Inaccurate BMI BRI BIA DXA Body Mass Body Roundness Bioelectrical Dual X-ray Index Index Impedance Analysis Absorptiometry Correlation Correlation Correlation Gold Coefficient Coefficient Coefficient Standard 0.60 to 0.70 0.80 0.78 to 0.93 Simple Measure App-deriv
Slide 16: There Is Still More that can be Done to Improve the Quality of Care
There Is Still More that can be Done to Improve the Quality of Care for People Living with Obesity • Blocking myostatin and Anti-myostatin-Induced Physical and Metabolic Changes Important to People living with Obesity other key TGF-beta ligands, including activin A, can Increased lean mass Reduction
Slide 17: Impact of Testosterone Ester on Body Composition and Weight
Impact of Testosterone Ester on Body Composition and Weight Obese and Overweight Obese Control (Untreated) Fat Mass: Lean Mass Fat Mass Lean Mass Android Fat Bone Minearl Ratio (kg, % of TM) (kg, % of TM) (% of Fat Mass) Content (kg, %CBL) 6.0 % Wt Loss 4.1 4.4 4.0 2.8 2.0 2.0 0.1 0.0 Testosterone E
Slide 18: Summary
Summary Obesity is excess and abnormal adipose tissue, not just excess weight GLP-1-associated incretins have demonstrated the ability to reduce total body weight at levels commensurate with bariatric surgery GLP-1 agonists are associated with excess lean mass loss, loss of bone density, and rapid w
Slide 19: LPCN 2401 P2 Results & Next Steps
LPCN 2401 P2 Results & Next Steps Dr. Ben Bruno VP of Clinical Development
Slide 20: Testosterone Therapy Reduces Weight, Improves Glycemia
Testosterone Therapy Reduces Weight, Improves Glycemia T therapy led to continued weight loss over 11-years T therapy prevented or reversed newly diagnosed T2DM in in obese men with lower T (N=474) 1 men without hypogonadism (N=1007)2 25 20 T 4 Change in OGTT (mM) 15 Placebo New Onset T2DM (%) * 10
Slide 21: Phase 2 Study in Patients with Obesity and Overweight
Phase 2 Study in Patients with Obesity and Overweight NCT04134091 study design Three-arm, blinded, placebo-controlled trial in male subjects with metabolic dysfunction associated steatohepatitis (n=56) Phase 2 Study Open Label Extension 36 weeks 36 weeks Treatment A: LPCN 2401 Treatment A: LPCN 2401
Slide 22: LPCN 2401 - Improvement in Body Composition
LPCN 2401 - Improvement in Body Composition Prespecified endpoints met – increased lean mass and decreased fat mass Body Composition Analysis Set1 Body Composition Results LPCN 2401 LPCN 2401+E Placebo Parameter at Baseline (N=13) (N=13) (N=14) Fat Mass:Lean Mass Ratio 4 Mean Age (years) 53.2 53.8 5
Slide 23: LPCN 2401 - Improvement in Body Composition
LPCN 2401 - Improvement in Body Composition Prespecified endpoints met – increased lean mass and decreased fat mass Fat Mass Lean Mass Total Fat Mass Trunk Fat Mass Lean Mass (% of TM) Appendicular Lean Mass (% of TM) (% of Trunk Mass) 5 * 2 1 * 4 * 0 0 3 Absolute CBL (%) 2 % CBL % CBL -2 -1 1 -4 -2
Slide 24: Impact of LPCN 2401, LPCN2401+Vitamin E, and Vitamin E on Fat mass
Impact of LPCN 2401, LPCN2401+Vitamin E, and Vitamin E on Fat mass Fat loss amplification of ARA in conjunction with Vitamin E Whole Body Fat Trunk Fat Total Fat Mass Trunk Fat Mass (% of TM) (% of Trunk Mass) 1 0.5 0 Placebo adjusted CBL (%) Placebo adjusted % CBL 0 -1 -0.5 -2 -3 -1 -4 -1.5 -5 -2 -
Slide 25: LPCN 2401 - Improvement in Bone Mass and Density
LPCN 2401 - Improvement in Body Composition Improvement in bone mass and bone density compared to placebo Bone Mass and Density Bone Mineral Content (%) Hip T Score Femoral Neck T Score 3.5 0.3 *,# *,# * Placebo-Adjusted % CBL 3 0.25 Placebo-Adjusted CBL 2.5 0.2 2 0.15 1.5 0.1 1 0.5 0.05 0 0 T-Ester
Slide 26: LPCN 2401 - Changes in Functional Tests
LPCN 2401 - Changes in Functional Tests Hand Grip Strength Ten Meter Walk Time 8 0 Change from Baseline (kg) 6 Change from Baseline (S) -0.5 4 2 -1 0 -1.5 -2 -4 -2 Baseline Grip Strength (kg) Walk Time (s) LPCN 2401 84.4 10.33 LPCN 2401+ E 88.5 8.67 Placebo 82.1 8.60 Data are mean (SE) Lipocine│Octo
Slide 27: Improved Liver Health
LPCN 2401 Improved Liver Health Liver Injury Marker Reduction1 Liver Fat Reduction at Week 12 (MRI-PDFF)2 LPCN 2401 LPCN 2401+E Placebo ALT AST ALP GGT 0 (N=19) (N=18) (N=19) 5 from Baseline (%) Absolute Change -2 -4 Change from Baseline (U/L) 0 -6 -5 -8 *,# # -10 *,# # -10 *,# *,# NASH Resolution w
Slide 28: LPCN 2401 - Differentiated Obesity Management Option
LPCN 2401 - Differentiated Obesity Management Option Well-tolerated with no safety signals upon 36-week exposure • POC study in relevant obese and overweight population • Frequency and severity of TEAEs, SAEs with LPCN 2401 were comparable to placebo • 4 subjects discontinued placebo due to TEAE vs.
Slide 29: LPCN 2401: Potential to Amplify Effects of Incretin Mimetics
LPCN 2401: Potential to Amplify Effects of Incretin Mimetics ARA may increase weight loss through increased expression and activity of GLP1R 4,5 GLP-1 expression increase with ARA2 Non-Diabetic Diabetic Insulin Androgen Receptor Incretin Sensitivity3 Agonist (ARA) Mimetic Diabetes6,7 β GLP-1 GLP-1 V
Slide 30: Testosterone Therapy in Women
LPCN 2401 in Women Potentially safe and effective intervention to improve body composition Women have ~1/15th the levels of testosterone compared to men Testosterone Therapy in Women • Typically, women have ~10x higher testosterone levels than estrogen levels Improved Body Composition10 • Testostero
Slide 31: Next Steps
Next Steps POC Clinical Development Objectives Investigate combination of LPCN 2401 (+/- Vitamin E) + incretin mimetic in proof-of-concept study • Potential additional fat/weight loss and less lean/bone mass loss with the combination compared to either monotherapies Determine impact of prior/continu
Slide 32: Concluding Remarks
LPCN 2401 Concluding Remarks Dr. Mahesh Patel President and CEO
Slide 33: LPCN 2401 - A New Paradigm in Oral Treatment for Obesity Management
LPCN 2401 - A New Paradigm in Oral Treatment for Obesity Management Target benefits to improve body composition Adjunct to GLP-1 agonist treatment Post cessation of GLP-1 agonist treatment Quality fat loss Quality weight loss Minimize fat regain Increase lean mass Weight loss Minimize weight rebound
Slide 34: LPCN 2401 - Potential for Differentiated Benefit to Risk Profile
LPCN 2401 - Potential for Differentiated Benefit to Risk Profile Key takeaways LPCN 2401 Competitive Landscape* • Oral, QD, prodrug of bioidentical hormone • Myostatin /activin receptor modulators (e.g. bimagrumab, • Fat loss amplification taldefgrobep, KER-065, and trevogrumab)1,2 • Lower fat mass
Slide 35: Q&A
LPCN 2401 Q&A LIPOCIN= ENHANCING HEALTH