C O R P O R AT E P R E S E N TAT I O N F E B R UA R Y 2 0 1 8 - - PowerPoint PPT Presentation

C O R P O R AT E P R E S E N TAT I O N F E B R UA R Y 2 0 1 8

CAUTIONARY STATEMENT

This presentation does not purport to be all-inclusive or comprehensive. Any information communicated regarding LB Pharmaceuticals (“the Company”), whether

• ral or written, is qualified in its entirety, for purposes of any investment in the

Company, by the information set forth in the Company’s confidential private placement memorandum, including, but not limited to, the risk factors described

• therein. This presentation does constitute an offer to sell securities to, or buy

securities from, anyone. The Company has made statements throughout this presentation which constitute forward-looking statements. These statements involve known and unknown risks, uncertainties and other factors that may cause its actual results, levels of activity, performance or achievements to be materially different from any results, levels of activity, performance or achievements expressed or implied by any such forward- looking statements. In some cases you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “could,” “expect,” “hopes,” “intends,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “likely,” “potential,” or “continue” or the negative of these terms and similar words. Although management believe that the expectations reflected in these forward-looking statements are reasonable, management cannot guarantee future results, levels of activity, performance or

• achievements. Furthermore, management undertakes no obligation to update any

forward-looking statements for any reason unless required to do so by law. 2

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 (approximately 1 in 10 attempt suicide, half are successful)

• LB-102 is a novel variant of Amisulpride, a schizophrenia drug

prescribed in dozens of countries ex-US for 30 years

• Biophysicochemical properties of LB-102 (structure, PK, CNS receptor

binding, animal behavior, rat toxicity) are consistent with Amisulpride

• Patent filed, should provide IP until 2037+
• 60 million Rx/year in US for SCZ
• Estimated 2% market share (Amisulpride share in EU) affords $1+

billion annual sales in US

• Rivopharm SA, world’s biggest supplier of Amisulpride, has

invested $850k to date in LB Pharmaceuticals and provides manufacturing support

• Complete IND package for LB-102 in 12 months

3

LB PHARMACEUTICALS INVESTMENT HIGHLIGHTS

• Amisulpride is a schizophrenia drug marketed in Europe since 1986
• Selective D2 (Ki = 2.8 nM)/D3 (Ki = 3.2 nM) antagonist
• 30 years of clinical use demonstrates an excellent safety/efficacy

profile

• LB-102 has a comparable selectivity profile to Amisulpride with no

discernible differences at key receptors (D2, D3, 5HT2, etc.)

• LB-102 rat 14-day toxicology profile is consistent with Amisulpride
• In head-to-head studies, LB-102 was comparable to or superior to

Amisulpride in three rodent schizophrenia models

4

AMISULPRIDE EU TRx

• 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 and Tiapride have a 2% and 1% market share in

the EU, respectively

5

AMISULPRIDE: AN OVERVIEW

6

DRUG SUCRA %

Clozapine 100

Amisulpride 92

Olanzapine 85 Risperidone 79 Paliperidone 65 Zotepine 61 Haloperidol 54 Quetiapine 48 Ariprazole 46 Sertindole 35 Ziprasidone 34 Chlorpromazine 33 Asenapine 32 Lurasidone 19 Iloperidone 17 Placebo

* Leucht et al. in Lancet , 2013, 382, 951-962.

SUCRA = Surface Under the Cumulative Ranking, a measure that compares efficacy of drug to an intervention that is always the best

Amisulpride is one of the most effective antipsychotics in the world.

COMPARATIVE EFFICACY OF 15 ANTIPSYCHOTIC DRUGS*

Recovery and remission rates in schizophrenia are comparable between Amisulpride and Clozapine

AMISULPRIDE EFFICACY

7

SOHO (SCHIZOPHRENIA OUTPATIENT HEALTH OUTCOMES) STUDY

0.00 20.00 40.00 60.00 80.00 100.00 120.00

% Responding Treatment Recovery Symptomatic Remission Functional Remission Adequate QOL

Olanza zapi pine Amisulpr pride de Ziprasido done Quetiapi pine Haloper erido dol 3 6 9 12 12

EUFEST STUDY

• Amisulpride had 2nd lowest

discontinuation rate

• In the Leucht meta-analysis, Amisulpride

had lowest odds of discontinuation among 15 antipsychotics

BBB NEARLY IMPASSABLE TO AMISULPRIDE

• Of 30 psychiatric medications tested Amisulpride was least able to

passively diffuse across Blood Brain Barrier (The AAPS Journal, 2014, 16, 1247-1258)

8

• 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 cLogP by 10%

LB-102

AMISULPRIDE SAFETY

9 WEIGHT GAIN, EXTRAPYRAMIDAL EFFECTS, AND SEDATION ARE MAJOR ISSUES IN SCZ DRUGS

• In a 43K patient meta-analysis* Amisulpride had fewer occurrences of

weight gain and sedation than Olanzapine, Quetiapine, and Risperidone (first-line standard of care), and less EPS than Risperidone

• Despite a strong record of efficacy and safety, Amisulpride is

unavailable to schizophrenia patients in the United States

* Leucht et al. in Lancet, 2013, 382, 951-962.

LB-102: A NOVEL BENZAMIDE

• LB-102 designed to improve delivery to the brain while minimally affecting

receptor binding

• PCT and US patent application (62/427062, filed November 2017) covers

composition of matter

• In vitro data suggests that LB-102 has greater membrane permeability than

Amisulpride

• LB-102 shows equivalent, and in some cases better, efficacy in animal models of

schizophrenia compared to Amisulpride

10

Amisulpride LB-102

MW = 369.5 cLogP = 3.94 MW = 383.5 cLogP = 4.41

LB-102 IN VITRO BRAIN PERMEABILITY DATA

• In PAMPA assay LB-102 was ~200X more permeable than

Amisulpride

11

LB-102 PHARMACOKINETICS

• 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

12

LB-102 RAT BRAIN D2/3 RECEPTOR OCCUPANCY

• Initial in vivo data suggests greater dopamine RO in rat brains
• In humans, dopamine RO is highly correlated to improvements

in PANSS

Dopamine % RO in rat brains (n = 3) 12h after PO doses of LB-102 or Amisulpride

13

LB-102 AND AMISULPRIDE RECEPTOR SPECIFICITY

COMPARISON TO MARKETED ANTI-PSYCHOTICS

Sedation/Weight gain (H1)

Ki data from: The Neuroscientist, 2000, 6, 252-26245rf

Sedation (M) Anxiety, Orthostasis (A) Weight gain (5HT2a/c) Antipsychotic Effect (D2) 14

IN-VIVO TOXICOLOGY CONSISTENT WITH AMISULPRIDE

• 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 (4 days)

15

• Final results of a 14 day Dose Range Finding Study in rats produced a

Maximum Tolerated Dose of 200mg/kg/d, consistent with Amisulpride

• In excess of 7x of doses that were effective in LMA and NOR rat

models of schizophrenia

mg/kg/dose mg/kg/day Survival Rate

100 200 100% survival 300 600 100% survival 600 1200 5/6 moribund, 1/6 found dead on day 2 1200 2400 5/6 died on day 2, 1/6 died on day 1

RESULTS OF LB-102 NON-GLP 4 & 14 DAY TOXICOLOGY STUDIES (MPI RESEARCH)

CATALEPSY STUDY

16

RAT BAR BALANCE STUDY (UNIVERSITY OF MANCHESTER)

• LB-102 was statistically indistinguishable from Amisulpride

NOVEL OBJECT RECOGNITION (NOR) STUDY

• NOR is a widely published and validated animal model that

measures rescuing of cognitive impairment by atypical anti- psychotics

• Unimpaired rats spend more time exploring novel versus

familiar objects. Dosing with PCP negates that preference, and is broadly correlated with cognitive impairment of humans

• In this model, approved atypical anti-psychotics restore the

ability of PCP impaired rats to discriminate between familiar and novel objects

• Study objective was to determine whether or not LB-102

restores cognition (study designed for binary results – not powered to show comparative efficacy between agents)

RAT EFFICACY STUDY (UNIVERSITY OF MANCHESTER)

17

NOR STUDY: DISCRIMINATION INDEX

18 Discrimination index ((time spent exploring novel – time spent exploring familiar)/total exploration time) + SEM (n = 10/group).

• 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 benzamides, LB-102 and 103, for the treatment of schizophrenia”, ECNP (European Neuropsychopharmacology, 2017, 27 (S4), S922-S923)

LOCOMOTOR ACTIVITY (LMA) STUDY

• LMA is a widely published and validated animal model that

measures the rescuing of hyperactivity by atypical anti- psychotics

• Amphetamine impaired rats display hyperactivity broadly

correlated with positive aspects of the human PANSS scale

• Approved atypical anti-psychotics in this model reduce

hyperactivity and restore movement of amphetamine impaired rats to normal levels

• Goal of this study was to determine whether or not LB-102

reduced hyperactivity associated with amphetamine

RAT EFFICACY STUDY (CHARLES RIVER DISCOVERY SERVICES)

19

LOCOMOTOR ACTIVITY (LMA) STUDY

Total ambulatory distance data from an amphetamine induced LMA rat study (n=10/group) measured 6 hours post-dose amphetamine dose over the course of an hour. Treatment groups marked with * were statistically superior to amphetamine (p < 0.01)

• LB-102 was statistically superior to Amisulpride in restoring normal

motion to amphetamine impaired rats at 30mg/kg (p < 0.05)

20

Study results presented as part of poster: “Pre-clinical evaluation of two novel benzamides, LB-102 and 103, for the treatment of schizophrenia”, ECNP (European Neuropsychopharmacology, 2017, 27 (S4), S922-S923)

MOUSE APOMORPHINE INDUCED CLIMBING (AIC) STUDY

• Apomorphine induces climbing in mice, replicative of

stereotypy (positive aspect) of PANSS scale

• Approved atypical anti-psychotics in this model return

movement of apomorphine treated mice to unimpaired levels MOUSE EFFICACY STUDY (BRAINS ON-LINE)

21

• LB-102 was statistically indistinguishable from Amisulpride (p > 0.05) LB-

102 and Amisulpride dosed p.o. in mice (n=8/group)

APOMORPHINE INDUCED CLIMBING STUDY

22

Study results presented as part of poster: “Pre-clinical evaluation of two novel benzamides, LB-102 and 103, for the treatment of schizophrenia”, ECNP (European Neuropsychopharmacology, 2017, 27 (S4), S922-S923)

ANIMAL BEHAVIORAL CONCLUSIONS

• LB-102 displayed efficacy in the three rodent models examined

(2 in rats, one in mice)

• Cognitive function, a negative aspect of schizophrenia
• Hyperactivity, a positive aspect of schizophrenia
• Stereotypy, a positive aspect of schizophrenia
• LB-102 with efficacy comparable to superior to Amisulpride

supports translation to clinical efficacy

23

LB-102: DEVELOPMENT MILESTONES

• Synthesis of 1 kg of racemic and S-enantiomer with purity > 95%



• LB-102 passive transport permeability study



• Extensive receptor selectivity studies comparable to Amisulpride



• US and PCT patent application filings covering LB-102



• Initial rat and mouse PK studies



• Rat PCP NOR proof of efficacy study



• Rat amphetamine induced locomotor activity (LMA) study



• Mouse apomorphine induced climbing (AIC) study



• Rat 14-day dose escalating toxicology study



• Rat PK-D2/3 receptor occupancy study



24

IND Opener enables Phase 2A POC. DDI studies help with inclusion/exclusion criteria and allow to determine if LB-102 is comparable to Amisulpride in DDI potential. IND could be filed on month 12 after study initiation (does not take into account contractual time spent choosing vendors).

IND ENABLING STUDY TIMELINE*

25

Study Jan-18 Feb-18 Mar-18 Apr-18 May-18 Jun-18 Jul-18 Aug-18 Sep-18 Oct-18 Nov-18 Dec-18 Pharmacology Receptor binding in vitro Receptor occupancy in vivo Microdialysis Safety Pharmacology CNS Pulmonary Cardiovascular PK In vitro stability Simulated Gastric Fluid Blood/Plasma Liv Mics/Hepat Met ID Pharmacokinetics In Vivo IV (2 species) PO Dose escalating (2 species) DDI potential CYP inhibition CYP inducction Transporter substrate Toxicology DRF 2nd species GLP rats GLP 2nd species Genotoxicity Bacterial mutagenicity In vitro chrom. aberration In vivo chrom. aberration

* Assumes Series A financing closes by 2/28/18

CLINICAL PROOF OF CONCEPT: PHASE 1/2A

• Phase 1: One week, ascending dose (50, 150, 400, 800 mg/d, based on

amisulpride), n ~ 32 healthy volunteers

• PK/PD/safety endpoints
• 200 mg/kg/d MTD in rats allometrically translates to 2300 mg/d in humans (3X

greater than typical Amisulpride dose of 800 mg/d)

• Start to finish time could be < 3 months
• Phase 2: Titrate to maximum dose over one week, n ~ 50 schizophrenia

patients (PANSS > 80)

• PANSS at 4 weeks primary endpoint, time to hospital discharge, and dopamine

receptor occupancy secondary endpoints

• Start to finish time could be < 1 year
• Potential for proof of concept data in under 2 years from IND filing

26

LB-102 SUMMARY

• LB-102 is a novel, minimally different, derivative of Amisulpride. PCT

and US patent applications were filed in November 2017 (affording IP to 2037+)

• LB-102 has a comparable target affinity and selectivity profile to CNS

receptors as Amisulpride

• LB-102 has a similar pharmacokinetic profile to Amisulpride in two

species and should be suitable for oral dosing in humans

• Preliminary in vivo data suggests that LB-102 displays better dopamine

receptor occupancy in rat brains

• In three well validated animal models (in two species) LB-102

showed similar or better efficacy compared with Amisulpride

• IND enabling package could be complete in a year
• Clinical proof of concept could be available 2 years later

27

Phase I Pre- clinical Phase II Phase III Market

LB-102

N-Methyl Amisulpride (racemic)

LB-103

N-Methyl Amisulpride (S-enantiomer)

LB-111

Orphan CNS Indication

Product Name Product Description

PRODUCT PIPELINE

DEVELOPING NOVEL VERSIONS OF EXISTING EFFECTIVE PSYCHIATRIC MEDICATIONS FOR US MARKET

28

FINANCING AND DEVELOPMENT PLAN OF ACTION

Series A Financing Q1 2018

• Conduct pre-IND meeting with FDA (scheduled)

Completed

• Initiate pre-clinical research on second CNS asset

Q2 2018

• Complete toxicology, ADME, and efficacy studies

Q3 2018

• File IND for LB-102

Q1 2019

• Expected IND Opening

Q2 2019

29

RIVOPHARM, SA

• Swiss based, 40+ year old generic manufacturer
• Believed to be the world’s largest manufacturer of Amisulpride
• Recently acquired a portfolio of 77 marketed generic, branded and

OTC products from Teva Pharmaceuticals

• Led 2016 and 2017 rounds of financing and plans to participate in

upcoming Series A financing (Q1 2018)

• Provides LB Pharma with extensive manufacturing and regulatory

guidance in support of LB-102

30

STRATEGIC PARTNER AND INVESTOR

MANAGEMENT

31

Vince Grattan, Co-Founder

• Board member and senior consultant to LB Pharmaceuticals.
• A PA registered pharmacist currently employed by MHM

Services, responsible for all facets of drug utilization management collaborating with a team of 300+ clinicians

• Has 20 years of experience in psychopharmacology

John M. Kane M.D.

Vice President, Behavioral Health Services North Shore – LIJ Chairman of Psychiatry at The Zucker Hillside Hospital

Stefan Leucht M.D.

Department of Psychiatry & Psychotherapy Technische Universitat Munchen, Germany

Ira Glick M.D.

Professor of Psychiatry and Behavioral Sciences, Stanford University School

• f Medicine

Daniel Levenson

MA, MHC-LP NYC practitioner treating individuals with intellectual disabilities

David Schatzkamer

LMHC, RPT NYC practitioner treating individuals with intellectual disabilities

• Dr. Andrew Vaino, CSO
• Former VP of R&D at Retrophin, Inc.
• Invented and brought drug to treat PKAN from idea to dosing

in humans in under 2 years

• PhD in Chemistry (Queen’s), MBA (UC Irvine)

Zachary Prensky, CEO & Co-Founder

• Experienced biotechnology and pharmaceutical investor
• Managed family office from 2000-2015
• Has 18+ year history of strategic consulting in the biotech

industry (Datascope, Caliper, Emisphere, Aldeyra and

• thers)

Advisory Board Marc Panoff, Chief Financial Officer

• Previously CFO of Retrophin - raised $150 million in equity

and debt financings and uplisted company to Nasdaq Global Market

• Previously CFO of Neurologix and Nephros