Lb Pharmaceuticals Inc · NASDAQ:LBRX
Lb Pharmaceuticals — Investor Presentation (January 2019)
30 slides from Lb Pharmaceuticals's investor presentation, January 2019
Slide 1: Corporate Presentation January 2019
C O R P O R AT E P R E S E N TAT I O N JANUARY 2019 Making Smart Chemical Changes to Create Improved Novel Therapeutics
Slide 2: Forward-Looking Statements
FORWARD-LOOKING STATEMENTS This presentation does not purport to be all-inclusive or comprehensive. Any information communicated regarding LB Pharmaceuticals (“the Company”), whether oral or written, is qualified in its entirety, for purposes of any investment in the Company, by the information set
Slide 3: LB Pharmaceuticals Investment Highlights
LB PHARMACEUTICALS INVESTMENT HIGHLIGHTS • CNS-focused development stage company intent on building a pipeline of improved versions of effective drugs that are commercially unavailable in the US • Lead asset LB-102 for the treatment of schizophrenia has potential, to yield in excess of $1 billion in
Slide 4: Management Team
MANAGEMENT TEAM Zachary Prensky, Chief Executive Officer & Co-Founder o Experienced biotechnology and pharmaceutical investor o Managed family office from 1997-2015 o Has 18+ year history of strategic consulting in the biotech industry (Datascope, Caliper, Emisphere, Aldeyra, and others) Andrew Vain
Slide 5: Board of Directors
BOARD OF DIRECTORS Zachary Prensky o Chief Executive Officer and Co-Founder, LB Pharmaceuticals, Inc. Isaac Blech o Biotechnology investor and entrepreneur o Co-Founder, Celgene Corporation, Genetic Systems Corporation, Icos Corporation, Nacuity Pharmaceuticals, Inc., Nova Pharmaceuticals Corporatio
Slide 6: Scientific Advisory Board
SCIENTIFIC ADVISORY BOARD John M. Kane, M.D., Chairman o Vice President, Behavioral Health Sciences, Northwell Health o Chairman of Psychiatry, Zucker Hillside Institue Robert Ruffolo, Ph.D., D.Sc. (h), D.Eng. (h), F.C.P.P. o Retired President of R&D, Wyeth Pharmaceuticals o Previously SVP and Direc
Slide 7: LB Pharmaceuticals Company Overview
LB PHARMACEUTICALS COMPANY OVERVIEW Making Smart Chemical Changes to Create Improved Novel Therapeutics • Lead drug, LB-102, is a methylated version of amisulpride (used in Europe for decades) that treats the multi-billion dollar disease schizophrenia • Novel chemical structure – biological/pharmaco
Slide 8: Examples of Methylation
EXAMPLES OF METHYLATION ao Cee oe 7 NH I I Amitriptyline (1961) Nortriptyline (1964) Imipramine (1957) % EE Catena ( (1998) Efffexor (1 993) Pristq (2008) O-N Risperdal (1993) Invega ( (2006) COs Y NH / Desipramine (1964) NC - ‘ NNN Lexapro (2002)
Slide 9: Schizophrenia
SCHIZOPHRENIA • Schizophrenia (SCZ) is a debilitating disease affecting 3 million Americans1 • Characterized by disorganized thought, social withdrawal, and cognitive deficits • SCZ patients have profoundly diminished qualities of life • On average, SCZ patients life expectancy is reduced by 12-15 y
Slide 10: Schizophrenia Landscape
SCHIZOPHRENIA LANDSCAPE • US market share1 by product similar to that of the EU2 • Amisulpride maintains an estimated 2% market share of antipsychotics for all indications in the EU (~ 2 million scripts per year2; steady usage over past 5 years) • Closely related sulpiride (another benzamide not ava
Slide 11: Amisulpride Background
AMISULPRIDE BACKGROUND • Amisulpride is a schizophrenia drug marketed in Europe since 1986 • Patented and developed by Synthélabo, a small French company acquired by Sanofi • Selective D2 (Ki = 2.8 nM)/D3 (Ki = 3.2 nM) and 5HT7 (Ki = 31 nM) antagonist • In a July 2000 press release, Sanofi stated th
Slide 12: Amisulpride Comparative Efficacy
AMISULPRIDE COMPARATIVE EFFICACY n = 43,000 meta-analysis of 15 SCZ drugs* Amisulpride is one of the most effective antipsychotics in the world EUFEST study, n = 498 clinical trial of 5 SCZ drugs** Amisulpride has one of the lowest discontinuation rates of any antipsychotic 0 3 6 9 12 Olanzapine Ami
Slide 13: Amisulpride Negative Symptoms and Depression
AMISULPRIDE NEGATIVE SYMPTOMS AND DEPRESSION Amisulpride’s ability to inhibit 5-HT7 provides anti-depressant properties… And renders it effective in treating negative symptoms of SCZ 13
Slide 14: LB-102: A Novel Benzamide
LB-102: A NOVEL BENZAMIDE Amisulpride LB-102 MW = 369.5 MW = 383.5 cLogP = 3.94 cLogP = 4.41 • LB-102 designed to improve delivery to the brain while minimally affecting receptor binding • US patent and PCT patent application (filed November 2017) cover composition of matter • In vitro data suggests
Slide 15: Why Methylate Amisulpride?
WHY METHYLATE AMISULPRIDE? • Comparable efficacy to risperidone and olanzapine (best-in-class antipsychotics) at treating symptoms of SCZ1 • Less sedation than nearly all other antipsychotics.1 In a recent retrospective cohort study, amisulpride was found to have lower risk of self-harm after SCZ di
Slide 16: LB-102 Designed to Improve BBB Permeability
LB-102 DESIGNED TO IMPROVE BBB PERMEABILITY • Of 30 psychiatric medications tested amisulpride was least able to passively diffuse across Blood Brain Barrier (BBB)* LB-102 • High doses of amisulpride may be responsible for some of its clinically relevant side effects • Addition of a single methyl gr
Slide 17: Amisulpride Comparative Safety
AMISULPRIDE COMPARATIVE SAFETY Data from 43,000 patient meta-analysis* *Leucht et al. Lancet, 2013, 382, 951-962 17
Slide 18: Amisulpride Safety
AMISULPRIDE SAFETY QT PROLONGATION Examples of QTc prolongation associated with select antipsychoticsa,b • All antipsychotics, amisulpride included, have the Approximate QTc interval potential to alter the QT interval prolongation in Antipsychotic millisecondsc • Pharmacovigilance data from UK from
Slide 19: LB-102 In Vitro Membrane Permeability Data
LB-102 IN VITRO MEMBRANE PERMEABILITY DATA In a PAMPA assay LB-102 was ~200X more permeable than amisulpride 19
Slide 20: LB-102 and Amisulpride Receptor Specificity
LB-102 AND AMISULPRIDE RECEPTOR SPECIFICITY Potent D2/3 and 5HT7 inhibitor Weight gain (5HT2a/c) Cognition/Depression (5HT7) Antipsychotic Effect (D2) Sedation/Weight gain (H1) Sedation (M) Anxiety, Orthostasis (A) Ki data from: The Neuroscientist, 2000, 6, 252-26245rf 20
Slide 21: LB-102 Pharmacokinetics Equivalent to Amisulpride
LB-102 PHARMACOKINETICS EQUIVALENT TO AMISULPRIDE • Total benzamide (LB-102 + amisulpride) plasma exposure of orally dosed LB- 102 is similar to amisulpride and is linearly dose dependent in rats and in mice • Note, LB-102 is ~50% demethylated to amisulpride in rodents • Demethylation likely CYP-dri
Slide 22: LB-102 Rat Brain D2/3 Receptor Occupancy
LB-102 RAT BRAIN D2/3 RECEPTOR OCCUPANCY (RO) Dopamine % Receptor Occupancy in rat brains (n = 3/group) 12h after PO doses of LB-102 or amisulpride • Initial in vivo data suggests greater dopamine RO in rat brains for LB-102 • In humans, dopamine RO is highly correlated to improvements in PANSS 22
Slide 23: Novel Object Recognition (NOR) Study
NOVEL OBJECT RECOGNITION (NOR) STUDY • NOR is a widely published and validated animal model of cognitive impairment in SCZ • Study results show LB-102 restored cognitive function to PCP impaired rats in a manner comparable to amisulpride Study results presented as part of poster: “Pre-clinical evalu
Slide 24: Locomotor Activity (LMA) Study
LOCOMOTOR ACTIVITY (LMA) STUDY • LMA is a widely published and validated animal model of hyperactivity in SCZ Total ambulatory distance data from an amphetamine induced LMA rat study (n=10/group) measured 6 hours post-dose amphetamine over the course of an hour. * p < 0.01 v control, ** p < 0.05 v a
Slide 25: Mouse Apomorphine Induced Climbing (AIC) Study
MOUSE APOMORPHINE INDUCED CLIMBING (AIC) STUDY • AIC is a widely published and validated animal model of stereotypy in SCZ • Study results show LB-102 restored movement to apomorphine impaired rats in a manner comparable to amisulpride Study results presented as part of poster: “Pre-clinical evaluat
Slide 26: In-Vivo Toxicology Consistent with Amisulpride
IN-VIVO TOXICOLOGY CONSISTENT WITH AMISULPRIDE RESULTS OF LB-102 NON-GLP 4 & 14 DAY TOXICOLOGY STUDIES (MPI RESEARCH) • Initial 4 day study included groups of 6 rats (3F/3M) treated with 200, 600, 1200, and 2400 mg/kg/d LB-102 • Rats dosed at 200 and 600 mg/kg/d survived for duration of experiment •
Slide 27: LB-102 Animal Study Conclusions
LB-102 ANIMAL STUDY CONCLUSIONS • LB-102 has PK profile indistinguishable from amisulpride • LB-102 has equivalent/superior dopamine receptor occupancy • LB-102 displayed efficacy in three rodent models examined (2 in rats, 1 in mice) • Cognitive function • Hyperactivity • Stereotypy • LB-102 effica
Slide 28: Clinical Proof of Concept: Phase 1/2
CLINICAL PROOF OF CONCEPT: PHASE 1/2 • Based on FDA guidance at pre-IND meeting, we believe P1 could be conducted with ~ 35 healthy volunteers • Single and multiple ascending doses, based on amisulpride’s known safety and PK profile • PK/PD/Safety endpoint • 200 mg/kg/d in rats equivalent to ~3x typ
Slide 29: LB-102 Summary
LB-102 SUMMARY • LB-102 is a novel antipsychotic closely related to amisulpride; US composition of matter patent granted in January 2019; PCT patent application filed in November 2017 currently being prosecuted (affording IP to 2037+) • In every measure of SCZ to date, LB-102 has been shown to be as
Slide 30: Thank You
pharmaceuticals THANK YOU
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