Lb Pharmaceuticals Inc · NASDAQ:LBRX
Lb Pharmaceuticals — Sachs Bio Capital USA Forum 2018
21 slides from Lb Pharmaceuticals's conference presentation, Mar 21, 2018
Slide 1: Sachs Bio Capital USA Forum
S A C H S B I O C A P I TA L U S A F O R U M MARCH 21, 2018
Slide 2: Cautionary Statement
CAUTIONARY STATEMENT 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 forth
Slide 3: LB Pharmaceuticals Investment Highlights
LB PHARMACEUTICALS INVESTMENT HIGHLIGHTS • Schizophrenia (SCZ) is a debilitating disease affecting 3 million Americans • Despite > a dozen approved drugs 60% of patients not adequately treated • LB-102 is a novel variant of Amisulpride, one of the most effective and safe schizophrenia drugs approved
Slide 4: Management and Advisory Board
MANAGEMENT Advisory Board John M. Kane M.D. Zachary Prensky, CEO & Co-Founder Vice President, o Experienced biotechnology and pharmaceutical investor Behavioral Health Services o Managed family office from 2000-2015 North Shore – LIJ o Has 18+ year history of strategic consulting in the biotech Chai
Slide 5: LB-102: An Improved Amisulpride
LB-102: AN IMPROVED AMISULPRIDE • Amisulpride is a schizophrenia drug marketed in Europe since 1986 • Selective D2 (Ki = 2.8 nM)/D3 (Ki = 3.2 nM) and 5HT7 (Ki = 31 nM) antagonist • 30 years of clinical use demonstrates an excellent safety/efficacy profile • LB-102 has a comparable selectivity profil
Slide 6: Amisulpride One of Most Effective SCZ Drugs
AMISULPRIDE ONE OF MOST EFFECTIVE SCZ DRUGS COMPARATIVE META-ANALYSIS (n = 43,000) OF 15 ANTIPSYCHOTIC DRUGS * Amisulpride is one of the most effective antipsychotics in the world. Amisulpride has one of the lowest discontinuation rates of any antipsychotic 0 3 6 9 12 Olanzapine Amisulpride Ziprasid
Slide 7: > 2 Million Annual Amisulpride EU Rx
> 2 MILLION ANNUAL AMISULPRIDE EU RX • Amisulpride maintains an estimated 2% market share of antipsychotics for all indications in EU • ~ 2 million scripts per year; steady usage over past 5 years • Closely related Sulpiride also has a 2% market share 7
Slide 8: Amisulpride Differentiating Factors
AMISULPRIDE DIFFERENTIATING FACTORS • As effective as gold standard second generation antipsychotics Risperidone and Olanzapine at treating symptoms of SCZ* • Fewer occurrences of weight gain and sedation than Olanzapine, Quetiapine, and Risperidone (first-line standard of care), and less EPS than R
Slide 9: BBB Issues Decrease Amisulpride Efficacy
BBB ISSUES DECREASE AMISULPRIDE EFFICACY • Of 30 psychiatric medications tested Amisulpride was least able to passively diffuse across Blood Brain Barrier* LB-102 • Addition of a single methyl group (i.e. Amisulpride to LB-102) to an amine can have a profound impact on BBB permeability by increasing
Slide 10: 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 • PCT and US patent application (filed November 2017) covers composition of matter • In vitro data suggests that
Slide 11: LB-102 In Vitro Brain Permeability Data
LB-102 IN VITRO BRAIN PERMEABILITY DATA • In PAMPA assay LB-102 was ~200X more permeable than Amisulpride 11
Slide 12: LB-102 and Amisulpride Receptor Specificity
LB-102 AND AMISULPRIDE RECEPTOR SPECIFICITY LB-102 cleanly binds D2/3 and 5HT7 receptors (like Amisulpride)---decreases off-target effects Potent D2/3 and 5HT7 inhibitor Weight gain (5HT2a/c) Cognition/Depression (5HT7) Antipsychotic Effect (D2) Sedation/Weight gain (H1) Sedation (M) Anxiety, Orthos
Slide 13: 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 • Note, LB-102 is ~50% demethylated to Amisulpride in rats • Demethylation likely CYP-driven and expected to be l
Slide 14: 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 14
Slide 15: Novel Object Recognition (NOR) Study
NOVEL OBJECT RECOGNITION (NOR) STUDY • NOR is a widely published and validated animal model of cognitive impairment in SCZ • LB-102 restored cognitive function to PCP impaired rats in a manner comparable to Amisulpride Study results presented as part of poster: “Pre-clinical evaluation of two novel
Slide 16: 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 17: 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 • LB-102 restored movement to apomorphine impaired rats in a manner comparable to Amisulpride Study results presented as part of poster: “Pre-clinical evaluation of two novel be
Slide 18: 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 m
Slide 19: 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, one in mice) • Cognitive function, a negative aspect of schizophrenia • Hype
Slide 20: Clinical Proof of Concept: Phase 1/2a
CLINICAL PROOF OF CONCEPT: PHASE 1/2A • Based on FDA guidance at pre-IND meeting, P1 could be done with < 30-40 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 typical human A
Slide 21: LB-102 Summary
LB-102 SUMMARY • LB-102 is a novel antipsychotic closely related to Amisulpride; PCT and US patent applications were filed in November 2017 (affording IP to 2037+) • LB-102 has as comparable target affinity and selectivity profile against CNS receptors as Amisulpride • LB-102 has a similar pharmacok
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