Slide 1: Corporate Presentation December 2021
C O R P O R AT E P R E S E N T AT I O N DECEMBER 2021 Making Smart Chemical Changes to Create Improved Novel Therapeutics
Slide 2: LB Pharmaceuticals Investment Highlights
LB PHARMACEUTICALS INVESTMENT HIGHLIGHTS CNS-focused biotech building a pipeline of potential best-in-class therapies for the US market Lead asset, LB-102, is a novel benzamide LB-102 has potential to leveraging the Novel, De-risked, exceed $1 billion in Large US Market annual US sales (based demons
Slide 3: Management Team
MANAGEMENT TEAM Zachary Prensky, Chief Executive Officer & Co-Founder • Managed family office from 1997-2015 • Portfolio responsibilities included oversight of all biotechnology investments Anna Eramo, M.D., Chief Medical Officer • Former Clinical and Medical Affairs head at Lundbeck • Has 18 years
Slide 4: Schizophrenia
SCHIZOPHRENIA • Schizophrenia (SCZ) is a chronic and debilitating disease affecting approximately 1% of the US population1 • Approximately 100,000 new SCZ patients diagnosed per year2 • SCZ patients have profoundly diminished quality of life • Fewer than 20% hold full-time employment; increased odds
Slide 5: US Antipsychotic Market Landscape
US ANTIPSYCHOTIC MARKET LANDSCAPE US Antipsychotic Market(1): ~67mm Retail TRx US Antipsychotic Market(1): ~$12bn Sales Abilify Other Branded (aripiprazole) 2% 1% Vraylar (cariprazine) Other Generic 1% 4% Quetiapine Latuda (lurasidone) Rexulti 32% 29% (brexpiprazole) 1% Quetiapine Invega 1% Invega (
Slide 6: Schizophrenia – Unmet Medical Need
SCHIZOPHRENIA – UNMET MEDICAL NEED • Despite 20+ FDA approved drugs, SCZ patients don’t get adequate help • An estimated 50% of patients with SCZ do not take their prescribed medications as directed1 • Up to 74% of SCZ patients cycle through multiple drugs within 18 months, with up to 60% failing to
Slide 7: Amisulpride Background
AMISULPRIDE BACKGROUND • Amisulpride is a benzamide marketed for the treatment of schizophrenia in Europe since 1986 • Patented and developed by Synthélabo (acquired by Sanofi) • Selective D2 (Ki = 2.8 nM)/D3 (Ki = 3.2 nM) and 5HT7 (Ki = 31 nM) antagonist • In July 2000 Sanofi announced it would dis
Slide 8: Amisulpride Comparative Efficacy/Safety
AMISULPRIDE COMPARATIVE EFFICACY/SAFETY Meta-Analysis of 32 Schizophrenia (SCZ) EUFEST Study(2) Drugs(1) (Clinical Trial of 5 SCZ Drugs in First Episode) (n = 53,500) (n = 498) Antipsychotic Efficacy All-Cause Discontinuation 1 0.9 Proportion Without Treatment Discontinuation 0.8 0.7 0.6 0.5 0.4 0.3
Slide 9: Amisulpride Comparative Safety
AMISULPRIDE COMPARATIVE SAFETY • All cause discontinuation combines efficacy and tolerability. When reported separately, more patients dropped out due to inefficacy (40%) than due to adverse events (20%) 9 * Lancet, 2019, 394, 939-951
Slide 10: LB-102 Overview
LB-102 OVERVIEW LB-102 is a methylated version of amisulpride Amisulpride (1983) LB-102 (2016) • Novel chemical structure with chemical properties designed to improve amisulpride’s safety and efficacy • Safe and well-tolerated in a (n = 64) Phase 1 clinical study • Three US and four ex-US compositio
Slide 11: LB-102 Key Differentiators
LB-102 KEY DIFFERENTIATORS • Superior efficacy than most recently launched antipsychotics • Minimal off-receptor binding (D2, D3, 5HT7) leading to low incidence of AEs • Potential use in patients with predominantly negative symptoms, depression, and Alzheimer’s psychosis • Amisulpride one of two dru
Slide 12: LB-102 and Amisulpride Receptor Specificity
LB-102 AND AMISULPRIDE RECEPTOR SPECIFICITY LB-102 is a selective D2/D3 /5HT7 antagonist with minimal off-target activity Potent D2/3 and Weight gain (5HT2a/c) 5HT7 inhibitor Cognition/Depression (5HT7) Antipsychotic Effect (D2) Sedation/Weight gain (H1) Sedation (M) Anxiety, Orthostasis (A) Notes:
Slide 13: LB-102: Enhancing Amisulpride's Product Profile
LB-102: ENHANCING AMISULPRIDE’S PRODUCT PROFILE • Of 30 psychiatric medications tested amisulpride was least able to passively diffuse across model BBB(1) • Improving BBB permeability could improve efficacy/decrease adverse events • Methylation has been shown to improve membrane permeability without
Slide 14: LB-102 Phase 1 Clinical Trial Overview
LB-102 PHASE 1 CLINICAL TRIAL OVERVIEW • Dosing: 5 single ascending dose (SAD) cohorts/3 multiple ascending dose (MAD, 1 week, BID dosing) cohorts • Endpoints: Safety and pharmacokinetics • Single Site: Medpace in Cincinnati, OH Single Ascending Dose (SAD) Multiple Ascending Dose (MAD) 1 week 200 mg
Slide 15: LB-102 Phase 1 Pharmacokinetics (SAD)
LB-102 PHASE 1 PHARMACOKINETICS (SAD) LB-102 exhibits favorable PK properties, with a half-life of 12+ hours and Tmax of 2-3 hours 15
Slide 16: Plasma Exposure of LB-102 > Amisulpride
PLASMA EXPOSURE OF LB-102 > AMISULPRIDE Rosenzweig(1) reported PK data on 18 healthy volunteers exposed to a single dose 50 mg amisulpride Plasma Concentration of Amisulpride 50mg LB-102 vs. 50mg Amisulpride 50 mg Amisulpride 50 mg LB-102 100 MW = 369.5 LogP = 1.7 Concentration (ng/mL) LB-102 10 1 M
Slide 17: LB-102 Phase 1 Adverse Events
LB-102 PHASE 1 ADVERSE EVENTS • Prolactin elevation (PRL), which was reversible and unassociated with clinical consequences, was observed at all doses, a consequence of dopamine receptor binding • Dosing in 200 mg/d MAD cohort was stopped after 3 days due to two occurrences of EPS (acute dystonia) •
Slide 18: Dopamine RO Directly Linked to Improvements in SCZ Patients
DOPAMINE RO DIRECTLY LINKED TO IMPROVEMENTS IN SCZ PATIENTS Dopamine Receptor Occupancy Dopamine RO a good predictor of PANSS improvement(1) Notes: (1) Source: The AAPS Journal, 2011, 13, 121-130 18
Slide 19: LB-102 Phase 1b PET Imaging Study
LB-102 PHASE 1b PET IMAGING STUDY (NCT04588129) • Dosing: Adaptive design with 4 cohorts of 4 healthy volunteers each ‒ Multiple PET scans per subject using 11C raclopride as tracer • Study Objectives: To confirm D2/D3 target engagement and inform Phase 2 dosing 50 mg n=4 100 mg n=4 n = 16 4 Healthy
Slide 20: Phase 1b - Cohorts 1-3, Single Dose
PHASE 1b - COHORTS 1 - 3, SINGLE DOSE • Subjects in Cohorts 1 (100 mg) and 2 (50 mg) were scanned at 2.5, 7.5, and 23.5 hrs post-dose • Subjects in Cohort 3 (75 mg) were scanned at 2.5, 23.5, and 47.5 hrs post-dose • Desired dopamine RO between 60% and 75% • Data suggests that LB-102 can be dosed on
Slide 21: Phase 1b - Cohort 4, Steady State
PHASE 1b - COHORT 4, STEADY STATE, 100 MG (N=2); 50 MG (N=2) • Subjects scanned 2.5, 7.5, and 23.5 hrs after 4 days QD dosing • Dopamine RO observed at 50 mg was in the desired range for an effective schizophrenia drug • 50 mg LB-102 afforded same dopamine RO as 400+ mg amisulpride per day 21
Slide 22: Phase 1b - Key Takeaways
PHASE 1b - KEY TAKEAWAYS • No reported SAEs or EPS • Dopamine receptor occupancy in desired range at 50 mg to 100 mg dose • Confirms hypothesis from Phase 1 study • Planned dosing for Phase 2 study: 50 mg and 75 mg, once per day • FDA guided LB could dose up to 200 mg/d in SCZ patients • Therapeutic
Slide 23: LB-102 Phase 2 Clinical Program
LB-102 PHASE 2 CLINICAL PROGRAM • Trial Size: Expecting to enroll ~300 SCZ patients at ~25 sites • Design: 2 doses LB-102 versus placebo (4 weeks duration, in-patient, double-blind, placebo controlled) • Primary Endpoint: Change in PANSS • Development plan will follow well-established criteria for F
Slide 24: LB-102 Clinical Development Projected Timeline
LB-102 CLINICAL DEVELOPMENT PROJECTED TIMELINE FY 2020 FY 2021 FY 2022 FY 2023 Study Size C ost Q1 Q2 Q3 Q4 1H 2H 1H 2H Phase 1a n = 64 $1.6 Completed SAD/MAD Phase 1b n = 16 $1.5 Completed PET Phase 2 n = 300 $40.0 CARC $2.5 CMC $1.0 Completed - Indicates expected data readout • Phase 1 and 1b stud
Slide 25: LB-102 US Market Opportunity
LB-102 US MARKET OPPORTUNITY • Expect LB-102 would be 3rd line SCZ treatment initially • Amisulpride/LB-102 differentiated by clean AE profile and strong efficacy for both positive and negative symptoms of the disease • Prescriptions in the EU exceed 2 million/year despite a lack of sales/marketing
Slide 26: Pipeline Expansion Potential
PIPELINE EXPANSION POTENTIAL LB-102 has the potential for clinical impact in areas outside of schizophrenia, such as depression Product Discovery Pre-Clinical Phase 1 Phase 2 Phase 3 Indication LB-102 (schizophrenia) LB-104 (depression) LB-102 (schizophrenia – negative symptoms) LB-102 (schizophreni
Slide 27: LB Pharmaceuticals Investment Highlights
LB PHARMACEUTICALS INVESTMENT HIGHLIGHTS CNS-focused biotech building a pipeline of potential best-in-class therapies for the US market Lead asset, LB-102, is a novel benzamide LB-102 has potential to leveraging the Novel, De-risked, exceed $1 billion in Large US Market annual US sales (based demons
Slide 28: Thank You
is THANK YOU