Slide 1: Oral LPCN 1148 Improves Sarcopenia and Clinical Outcomes in Patients with Decompensated Cirrhosis
ORAL LPCN 1148 IMPROVES SARCOPENIA AND CLINICAL OUTCOMES IN PATIENTS WITH DECOMPENSATED CIRRHOSIS Benjamin J Bruno}, Joshua C Weavil’, Jonathan Ogle!, Nachiappan Chidambaram}, Elizabeth J Carey”, Christopher J Danford3, Zachary P Fricker’, Joseph S Galati, William M Lee®, Parvez S Mantry’, Kirti She
Slide 2: 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 3: Sarcopenia is commonly present in those with decompensated cirrhosis and impacts clinically meaningful outcomes
Sarcopenia is commonly present in those with decompensated cirrhosis and impacts clinically meaningful outcomes How patients feel: * Health related quality of life How patients function: * Frailty * Activities of daily living How patients survive: * Hepatic encephalopathy * Mortality * Peri-transpla
Slide 4: Multiple mechanisms contribute to sarcopenia in cirrhosis
Multiple mechanisms contribute to sarcopenia in cirrhosis Leucine" Exercise” Testosterone” Linked to muscle mass Inhibits myostatin Td Modulates mTOR Increases protein synthes Decreases turnover Vv mTOR - 90% of males with ‘SATELLITE CELL PROLIFERATION - A AND DIFFERENTIATION cirrhosis have low test
Slide 5: LPCN 1148: A novel MOA for management of cirrhosis
LPCN 1148: A novel MOA for management of cirrhosis Product . Oral androgen receptor agonist Candidate Dosage form comprising testosterone dodecanoate, a unique prodrug of the endogenous hormone Attributes Targeted Mechanism of Action Increase muscle mass and Via Improved liver function® and Induce h
Slide 6: Central Hypothesis: LPCN 1148 will improve sarcopenia
Central Hypothesis: LPCN 1148 will improve sarcopenia, sarcopenia related outcomes and clinically significant outcomes in patients with cirrhosis
Slide 7: Aims and objectives
Aims and objectives Specific Aims * To perform a phase 2 proof of * To generate proof of concept of concept study to establish the overall benefit of LPCN 1148 to short term safety and efficacy of support further development of LPCN 1148 in male patients with this drug in the study population advanc
Slide 8: Study population
Study population Inclusion criteria Exclusion criteria * Adult males * Failure to obtain consent * Cirrhosis * Active severe encephalopathy * Sarcopenia — defined by BMI- * Active infection adjusted SMI* * Uncontrolled or recurrent Gl * Listed for liver transplantation bleed in past 6 months * Prior
Slide 9: Study Design
Study Design: * Two-arm (1:1 randomization, N=29) * Oral LPCN 1148, T dodecanoate, vs. Placebo * Standard of care treatments/therapies allowed * 24-week placebo-controlled * Followed by 28-week open-label extension (OLE) * All subjects receive LPCN 1148 during OLE SCREENING <—_——_ TREATMENT: 52 WEEK
Slide 10: Endpoints
Endpoints Secondary endpoints ry endpoint (p value not adjusted for multiplicity) Pri * Baseline-adjusted change in Skeletal * Feel and function: Muscle Index (L3 region, L3-SMI) at * 6 min walk test Week 24 in LPCN 1148 treated * patient reported outcomes (PGI-C) participants compared to placebo su
Slide 11: Baseline characteristics
LPCN 1148 Baseline characteristics LPCN 1148 Placebo (N=15) et) Age (years) 58.347.5 58.849.5 BMI (kg/m?) 29.2453 29.0486 Placebo L3-SMI (cm?/m2) 47.8 47.0 44.8485 MELD Score 15.9 43.7 18.124.6 Medical History 2 1 Decompensation Event* 14 (93%) 14 (100%) 2 2 Decompensation Event 13 (87%) 12 (86%) He
Slide 12: Subject disposition and analysis data-sets
Subject disposition and analysis data-sets LPCN 1148 Placebo Subject Disposition (N=15) Completed Week 24 15 Withdrawal of informed consent post liver transplant 0 7 Death 0 1 Hospitalized 0 i Analysis Datasets (N=15) Safety set* 16 Modified Intent to Treat (mITT)** 15: No post-baseline CT scan 0 3
Slide 13: Change in L3-SMI (cm2/m2)
Change in L3-SMI (cm?/m?) Primary endpoint was met- improvement in skeletal muscle index L3-SMI Absolute Change from Baseline Week 12 + 2.64 0. _ 13-SMI Absolute Change From Baseline Placebo Subjects Week 24 at a £2 Placebo 1148 3.62 E S fa 4 rs 2 é & GLPCN 1148 G Placebo 0.74 14 9 45 10 Week LS mea
Slide 14: Further recurrence of overt hepatic encephalopathy was decreased with LPCN 1148
Further recurrence of overt hepatic encephalopathy was decreased with increased time to recurrence with LPCN 1148 LPCN 1148 Placebo Parameter (N=15) (N=14) Total decompensation events a 10 Total decompensation events > Grade 1 6 10 Hepatic encephalopathy events 3 6 HE > Grade 1 2* 6 Recurrence of HE
Slide 15: LPCN 1148 improved patient reported outcomes
LPCN 1148 improved patient reported outcomes Patient Global Impression of Change (PGI-C) Scale Please choose the response below that best describes the overall change in your symptoms since you started using the study treatment. 1) Very much better 2) Moderately better 3) Alittle better 4) No change
Slide 16: LPCN 1148 improved anemia in cirrhosis
LPCN 1148 improved anemia in cirrhosis . LPCN 1148 P-value Hemoglobin LPCN 1148 Placebo 5 = Change from (N=15) (N=13) Timepoint y Baseline NGsAEG oo Baseline (g/dL) 11.39 (0.84) 13.04 (0.66) NIA NS Week 24 CFB (g/dL) 1.30 (0.40) — -0.16 (0.23) 0.003 0.005 Mean (SE) 5 LPCN 1148 Placebo Anemia Status
Slide 17: LPCN 1148 produced trends in improvement in other secondary end-points
LPCN 1148 produced trends in improvement in other secondary end-points Parameter LPCN 1148 Deaths (n) 0 1 Days in hospital (total) 54 17 Length of hospital stay (median, days) 3 5 6 min walk test (feet)* 270 -16 EncephalApp Stroop Test (total time, seconds)* 4.8 13.8 *mean change from baseline (SE),
Slide 18: LFI: Observed change from baseline comparable to placebo
LFl: Observed change from baseline for LPCN 1148 is comparable to that of placebo at 24 week study duration | LPCN 1148 P-value _| 1148 P-value LPCN 1148 Placebo |-— i oo (N=15) (N=12) ange Tm | Vs, Placebo Timepoint Baseline Baseline 4.04 (0.23) 3.88 (0.34) Week 24 CFB -0.05 (0.18) -0.17 (0.17) Mea
Slide 19: LPCN 1148 - AE profile
LPCN 1148 - AE profile LPCN 1148 Placebo Parameter (N=15) (N=14) # n # n Total AEs 33 8 36 10 Serious AEs 15 5 16 5 Severe AEs 6 4 10 4 * Administration of LPCN 1148 was well tolerated in this end-stage population, with rates and severities of adverse events (AEs) similar to those within the placebo
Slide 20: Summary and conclusions
Summary and conclusions * LPCN 1148, an oral androgen receptor agonist improved sarcopenia in adult male patients with cirrhosis. ¢ It was further associated with improvement in encephalopathy, anemia, total number of days hospitalized, and patient reported outcomes which are all clinically meaningf
Slide 21: Acknowledgements
Acknowledgements * We acknowledge the contribution of all of the investigators and staff for this trial and express our gratitude to the patients who participated in this study
Slide 22: LPCN 1148 improved myosteatosis
LPCN 1148 improved myosteatosis Muscle Quality CBL Week 24 20 * 10 ° IMAT @HQM Relative Change in Muscle Areas (%) 8 6s -30 ” 1148 Placebo Substantial Changes in Muscle Quality seen with LPCN 1148 Therapy * Decrease in intramuscular adipose tissue (IMAT) * Significant increase in high quality muscle