Palisade Bio, Inc. · NASDAQ:PALI
Palisade Bio — Neuralstem — Investor Presentation (February 2017)
41 slides from Palisade Bio's investor presentation, Feb 27, 2017
Slide 1: February 2017 Corporate & Clinical Overview
February 2017 Corporate & Clinical Overview
Slide 2: Safe Harbor Statement
Safe Harbor Statement Although we believe that we have a reasonable basis for each forward - looking statement contained in this presentation, we caution you that forward - looking statements are not guarantees of future performance and that our actual results of operations, financial condition and
Slide 3: Overview
Overview 3 Cell Therapy: NSI - 566 • Regionally specific stem cell - lines Proprietary Screening Platform Lead asset: NSI - 189 • Small molecule drug discovery Human - derived stem cells platform technology Regionally specific for the development of CNS therapies Small molecule development capabilit
Slide 4: Key Highlights
Key Highlights • Neuralstem Corporate Strategy – Business development initiatives – Tianjin Pharmaceuticals Group $20mn strategic investment • Cash runway into 2018 • Lead Program: Novel Neurogenic Small Molecule – NSI - 189 Phase II MDD efficacy d ata expected in 3Q 2017 – NSI - 189 Phase II MDD lo
Slide 5: Pipeline
Pipeline 5 Neuralstem’s proprietary technology uses regionally specific neural stem cells for the development of CNS therapies.
Slide 6: Major Depressive Disorder
NSI - 189 Major Depressive Disorder
Slide 7: Overview
NSI - 189 Overview • New Chemical Entity (NCE) • Novel neurogenic MOA • Highly stable and well characterized • MDD Market Opportunity • Unsatisfied patient population* • High patient turnover rate in MDD* • Strong IP position through 2024 – 2034 • Efficacy: • Compelling Phase Ib MDD randomized, doub
Slide 8: Scientific Advisory Board
NSI - 189 Scientific Advisory Board Dr. Maurizio Fava Harvard, MGH, Executive Vice Chair, Dept. of Psychiatry Principal Investigator: NSI - 189 Phase 2 MDD clinical trial Dr. Michael Thase Univ. of Pennsylvania, Chief. Division of Mood and Anxiety Disorders Treatment and Research Program Dr. Mark Fr
Slide 9: MDD Market Opportunity
TRD II - Adjunct Rx - Rx Switch - Other 4 th / 5 th - New combos TRD I - Rx Switch - Adjunct Rx - SSRI / SNRI First Line - Monotherapy - SSRI/NSRI MDD Market Opportunity Large Patient Rx Turnover, Low Barrier to Entry, Adjunct/Mono Market Opportunities 67% p t. failure 75% p t. failure 80% p t. fail
Slide 10: MDD Phase Ib trial design
Cohort 1 N=8 (6 drug, 2 placebo) 40 mg QD Cohort 2 N=8 (6 drug, 2 placebo) 40 mg BID Cohort 3 N=8 (6 drug, 2 placebo) 40 mg TID Acute treatment: 28 days Drug free observational follow up: days 35, 42, 49, 56, 70, 84 NSI - 189 MDD Phase Ib trial design NSI - 189 Phase Ib double - blind, randomized, p
Slide 11: MDD Phase Ib results
NSI - 189 MDD Phase Ib results p=0.02 d=0.90 Study Day -20 0 20 40 60 80 100 Symptoms of Depression Questionnaire 2.0 2.2 2.4 2.6 2.8 3.0 3.2 3.4 3.6 3.8 Placebo NS-189 NS-189 1x per day NS-189 2x per day NS-189 3x per day p=0.03 d=1.10 Day 84 Day 28 Symptoms of Depression Questionnaire (SDQ) p=0.09
Slide 12: MDD Phase Ib clinical results
p=0.01 d=0.94 Study Day -20 0 20 40 60 80 100 Cognitive and Physical Functioning Questionnaire 2.0 2.5 3.0 3.5 4.0 4.5 5.0 Placebo NS-189 NS-189 1x per day NS-189 2x per day NS-189 3x per day p<0.01 d=1.20 Day 28 Day 84 NSI - 189 MDD Phase Ib clinical results All: A Phase 1B, Randomized, Double - Bl
Slide 13: MDD Phase Ib: Adverse Events
NSI - 189 MDD Phase Ib : Adverse Events 13
Slide 14: Favorable DMPK Characteristics
Favorable NSI - 189 DMPK Characteristics 14 Human PK supports QD dosing in clinic • t 1/2 is 17 - 20 hours • Total clearance is low (less than hepatic blood flow) • No gender difference in exposure profiles • No difference in AUC and t 1/2 between fasted and fed states Attractive metabolic profile •
Slide 15: Upcoming Phase II MDD Trial
NSI - 189 Phase 2 MDD Trial 15 Study Objectives • Primary: Montgomery - Asberg Depression Rating Scale (MADRS ) • Secondary: SDQ , HAMD17, CGI - S, CPFQ, SFI, Cogscreen Battery, Cogstate Brief Battery Innovative Study Design • Randomized, double blind, 3 cohorts (n=220): 40mg BID, 40mg QD, & placebo
Slide 16: Preclinical Data & MOA Insight
NSI - 189 Preclinical Data & MOA Insight 16
Slide 17: Mouse Depression Models: Chronic Novelty Suppressed Feeding
Chronic Novelty Suppressed Feeding (Mouse) 17 Latency to eat (sec) 0 100 200 300 400 500 600 Water Imipramine 60 mg/kg Vehicle NSI-144 NSI-150 NSI-158 NSI-189 Latency to eat (sec) 0 100 200 300 400 500 600 * * * N=15 - 20/group; PsychoGenics , Inc. Effects of 28 - days of dosing of Neuralstem lead
Slide 18: Neurogenic Effects and HI Volume Changes (Mouse)
Neurogenic Effects and HI Volume Changes in a Chronic Novelty Suppressed Feeding Model* (Mouse) *Neuralstem leads were dosed at 30 mg/kg and imipramine at 60 mg/kg for 28 days by oral gavage ( PsychoGenics , Inc.) NSI - 189 Mouse Depression Models 18
Slide 19: Mouse Depression Models: Dose Activity
NSI - 189 Doses of 10 - 100 mg/kg Activity Chronic Novelty Suppressed Feeding Model (Mouse ) Latency to eat (sec) 0 150 300 450 600 750 900 1050 1200 Water Imipramine 60 mg/kg NSI-189 3mg/kg NSI-189 10mg/kg NSI-189 30mg/kg NSI-189 100mg/kg * * * * • NSI - 189 (10 - 100 mg/kg) and imipramine signific
Slide 20: Neurogenic Effects and HI Volume Changes (Mouse)
Neurogenic Effects and HI Volume Changes in a Chronic Novelty Suppressed Feeding Model* (Mouse ) *NSI=189 had been orally dosed for 28 days NSI - 189 Mouse Depression Models 20 Depression (10 - 100mg/kg) ≠ Neurogenesis (10mg/kg) ≠ HI Volume Increase (30mg/kg)
Slide 21: Pipeline Update & MOA insight
Pipeline Update & MOA insight 21 • Restores LTP in Angelman Syndrome mouse • MOA : Enhances short - term and long - term potentiation in normal mice • Reversal of cognitive deficit in irradiated mice • Type 1 & 2 diabetic neuropathy reversal and prevention • MCAO stroke in rats data provide a wider
Slide 22: Preclinical Stroke in Rat
NSI - 189 Preclinical Stroke in Rat • NSI - 189 treatment from 6 hours post stroke for 12 weeks significantly ameliorated motor and neurologic deficits in a rat MCAO model of ischemic stroke. • This neuroprotective effect by NSI - 189 was accompanied by increased cell proliferation in the peri - inf
Slide 23: Preclinical Stroke in Rat: Treatment Groups
Group Treatment A 12 Week - Control (Stroke + Vehicle) B 12 Week - Experimental (Stroke + NSI - 189) C 24 Week - Control (Stroke + Vehicle) — No treatment D 24 Week - Experimental (Stroke + NSI - 189) — No treatment NSI - 189 Preclinical Stroke in Rat 23
Slide 24: Preclinical Stroke in Rat: MAP-2 Density
MAP - 2 Density in the cerebral cortex and hippocampus after NSI - 189 treatments: A. MAP - 2 in Cerebral cortex 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 12 Week- Control 12 Week NSI- 189 (30mg/kg) 24 Week- Control 24 Week NSI- 189 (30mg/kg) MAP - 2 Density (pixel Intensity/um 2 ) MAP - 2 in Cerebral Cortex
Slide 25: Type 1 & 2 Diabetic Neuropathy Results
NSI - 189: Type 1 & 2 diabetic neuropathy NSI - 189 induced Type 1 diabetes prevention & i nvention results • NSI - 189 significantly protected nerve function and structure in mice when given at the beginning of disease • NSI - 189 improved the nerve function and structure given eight weeks after di
Slide 26: Preclinical Type 1 & 2 Neuropathy Summary
NSI - 189 Preclinical Type 1 & 2 neuropathy Summary of NSI - 189 activities against Peripheral Neuropathy in Mouse Models of Diabetes *Prevention means test agent was given from the onset of diabetes. Intervention means test agent was given 7 - 8 weeks after the onset of diabetes. ND = not determine
Slide 27: Preclinical Type 1 & 2 Neuropathy: Nerve Fiber Density
27 Intra - Epidermal Nerve Fiber (IENF) Density & Sub - Epidermal Nerve Plexus (SNP) Density Sub - Basal Nerve Plexus (SBNP) Density & Stromal Nerve Density in Cornea NSI - 189 Preclinical Type 1 & 2 neuropathy Poster: “ Therapeutic Efficacy of NSI - 189 in Diabetic Mice, ” Calcutt , et al.
Slide 28: Irradiation-induced cognitive dysfunction
Exp tDa y 1 3 6 5 4 0 3 1 3 3 61 62 Three arms (Long - evans rats, n=16 per group): - Sham irradiation (IRR) + vehicle - Irradiation + vehicle - Irradiation + NSI189 IRR IRR IRR Daily NSI189 BrdU Behavioral testing Histolog y - NSI189 administered 30mg/kg/day PO - Animal cohorts completed each behav
Slide 29: Irradiation-induced cognitive dysfunction: Memory Tasks
Spatial Cognitive Impairment Novel Place Recognition Task Episodic Memory Retention Novel Object Recognition Task Spatial Memory Retention Object in Place Task Spatiotemporal Episodic Memory Retention Temporal Order Task p<0.05 p<0.05 p<0.05 p<0.05 p<0.05 p<0.05 p<0.05 NSI - 189 Irradiation - induce
Slide 30: Understanding LTP and Memory
Understanding LTP and Memory • For mechanistic studies: cognition = memory • LTP is a cellular biomarker of memory – repetitive, high - frequency stimulus leads to long - lasting synaptic transmission – increased LTP means enhanced memory, decreased LTP means memory deficit. • LTP occurs in hippocam
Slide 31: Enhances LTP magnitude
NSI - 189 enhances LTP magnitude 31 TBS after 2.5 h incubation 0 50 100 150 200 250 300 350 -10 -5 0 5 10 15 20 25 30 35 40 WT-Vehicle WT-NSI189 Vehicle EPSP slope (% of baseline) TBS after 3.5 h incubation 0 50 100 150 200 250 300 350 -10 -5 0 5 10 15 20 25 30 35 40 WT-Vehicle WT-NSI189 Vehicle Tim
Slide 32: Angelman Syndrome
NSI - 189: Angelman Syndrome 0 50 100 150 200 250 -10 -5 0 5 10 15 20 25 30 35 40 AS WT-vehicle AS-NSI189 EPSP slope (% of baseline) Time (min) NSI - 189 restores STP & LTP in Angelman Syndrome Mice Confirmatory model in a genetic disease By courtesy of Yan Liu 1 , Xiaoning Bi 1 , Michel Baudry 1 We
Slide 33: LTP-based assay and molecular pathway
LTP - based assay, NSI - 189’s molecular pathway NSI - 189 increases LTP magnitude in a time - dependent and concentration - dependent manner – This effect is not from increased synaptic transmission or NMDA receptor properties – This effect occurs within 1 - 3.5 hours of treatment (not before) – Th
Slide 34: Mechanism of Action: Dynamic transcriptional enhancer?
NSI - 189 Mechanism of Action: Dynamic transcriptional enhancer? Gronemeyer H, Gustafsson JA, Laudet V. Principles for modulation of the nuclear receptor superfamily. Nat Rev Drug Discov . 2004 Nov;3(11):950 - 64. Review. PubMed PMID: 15520817. Guzman - Karlsson MC, Meadows JP, Gavin CF, Hablitz JJ,
Slide 35: Limited epigenetic pathways
Limited epigenetic pathways DNA methylation & histone acetylation/deacetylation of DNA are dynamically regulated – leads to changes in protein synthesis and strength of neuronal connectivity mRNA regulation at pre/post - synaptic ending modulates synaptic scaling – c hanges neurotrophic factors, ion
Slide 36: Stem Cell Overview
ie Stem cell Overview
Slide 37: Cell Therapy Program Update
Cell Therapy Program Update 37 • Phase I stroke completed dosing all 9 patients and currently evaluating safety • cSCI is currently evaluating 4 Phase 1 thoracic patients; additional Phase 1 trial evaluating (Group B) 4 cervical patients • ALS Phase 1 & 2 follow - up evaluation
Slide 38: Stem Cell Overview
Stem cell Overview Technology: committed human neural stem cells • tissue restricted • give rise to neurons, astrocytes, oligodendrocytes • manufactured under GMP conditions for clinical applications • over 500 lines isolated from diverse areas of fetal human CNS Stem cell therapies: transplanted al
Slide 39: POC of cell survival
NSI - 566 POC of cell survival 39 Long term cell survival in 6 autopsy patients • Survival of up to 2.5 yrs • 4 cases of “nests” of round cells with cytoplasm • Neural differentiation • Maintenance of cell markers Patient number Gender # of days on FK506 # of days on MMF # of Days IM Meds Discontinu
Slide 40: Management
Management 40 Richard Daly, CEO • President, AstraZeneca Diabetes, US; President, BMS Diabetes, US; EVP , Takeda Pharmaceuticals; VP, Commercial Strategy, TAP Pharmaceuticals • Boards: Catalyst Pharmaceuticals; Synergy Pharmaceuticals • Education: MBA, Kellogg Graduate School of Management; BS, Micr
Slide 41: Key Highlights
Key Highlights • Near term milestones: – Phase II MDD clinical trial ; results expect in 3Q 2017 – Phase II MDD long term durability follow - up study 1H 2018 • Tianjin Pharmaceutical Group $20mn strategic investor – Cash runway into 2018 • Improved capital structure • B usiness development initiati