Neurotrope — Investor Presentation (February 2016)
35 slides from Neurotrope's investor presentation, Feb 23, 2016
Slide 1: Improving the lives of patients with Alzheimer's Disease and other Cognitive and Neurodevelopmental disorders
Improving the lives of patients with Alzheimer’s Disease and other Cognitive and Neurodevelopmental disorders February 2016
Slide 2: Safe Harbor Statement
2 Certain statements in this presentation, particularly those pertaining to our strategy, constitute forward - looking statements . Such statements are based upon the current beliefs and expectations of management and are subject to significant risks and uncertainties . Actual results may differ mat
Slide 3: Overview
Overview ; Attacking Alzheimer’s disease (AD) with a disruptive therapy – with the objective of reversing disease and slowing progression ; Neurotrope’s Bryostatin approach uses novel mechanisms for treatment of cognitive and neurodevelopmental disorders through Protein Kinase C (PKC) activation, wh
Slide 4: The Neurotrope Story
The Neurotrope Story ; Founded in 2013 to develop and commercialize Bryostatin as a disruptive approach with the potential to reverse AD ; Patented technology licensed from Blanchette Rockefeller Neurosciences Institute (BRNI) ; Over $200 million invested in R&D by the NINDS of the NIH and BRNI; $40
Slide 5: Large and Growing Alzheimer's Market
Large and Growing Alzheimer’s Market ; 5.1 million Americans age 65+ with Alzheimer’s Disease in 2015; projected to reach 7.1 million by 2025 and 13.8 million by 2050 ; Estimated 700,000 Alzheimer’s deaths among Americans age 65 and older in 2015 ; Alzheimer’s deaths increased 71% from 2000 to 2013
Slide 6: Bryostatin Milestones
6 Bryostatin Milestones 2016 First patients dosed in Phase 2b trial 2005 - 2011 Annual NCI safety data available; total >1,400 patients 2012 Neurotrope formed 2013 First financing completed First FDA compassionate use treatment approved 2014 FDA approves Phase 2a trial protocols FDA approves multi -
Slide 7: Bryostatin Background
Bryostatin Background ; Derived from marine organism, Bugula Neritina ; Pioneering science published by CSO, Dr. Daniel Alkon, former Chief, Laboratory of Adaptive Systems, National Institutes of Neurological Diseases and Stroke at NIH; Scientific Director of BRNI; Toyota Chair in Neurodegenerative
Slide 8: Bryostatin and PKC ε Activation
Bryostatin and PKC ϵ Activation ; Studies demonstrate that PKC ϵ plays a pivotal role in learning and memory ; Bryostatin , a small molecule, penetrates the blood - brain barrier and activates PKC ϵ , resulting in ; Improved synaptic function ; Promotion of new synapse formation ; Maturation of imma
Slide 9: Developmental History
Developmental History ; Preclinical work at BRNI demonstrated improved memory and learning in two different AD mouse models and several other animal models ; Clinical Work ; Safety data from >1,400 patients in NCI - sponsored clinical trials ; FDA approved several Compassionate Use protocols in seve
Slide 10: Phase 2b Clinical Trial Design
Phase 2b Clinical Trial Design ; 150 moderately severe to severe AD patients across 30+ sites in the U.S. ; First patients dosed January 2016 ; Primary efficacy endpoint based on Severe Impairment Battery Scale (SIB) ; Secondary efficacy endpoints – Activities of Daily Living (ADL), Neuropsychiatric
Slide 11: Phase 2b Clinical Trial Dosing Regimen
Phase 2b Clinical Trial Dosing Regimen 11 20 µg (50 Patients) 24 24 20 20 20 20 20 24 24 20 20 20 20 20 48 48 40 40 40 40 40 40 µg (50 Patients) 48 48 40 40 40 40 40 48 48 40 40 40 40 40 20 20 20 20 20 20 20 Placebo (50 Patients) 12 12 10 10 10 10 10 Pbo Pbo Pbo Pbo Pbo Pbo Pbo Pbo Pbo Pbo Pbo Pbo P
Slide 12: Approved Alzheimer's Drugs Landscape
12 COMPANY DRUG PROFILE CLINICAL STAGE MARKET CAP* Aricept (donepezil) • Delays progressive cognitive decline • All stages • Enhance cholinergic transmission by inhibiting enzyme acetylcholinesterase FDA Approved PFE: $183.3B Razadyne (galantamine) • Mild to moderate AD • Enhances cholinergic functi
Slide 13: AD Competitive Landscape
13 COMPANY DRUG PROFILE CLINICAL STAGE MARKET CAP* Azeliragon (TTP488) • Slow the rate of clinical progression • Mild to moderate AD • Eliminate amyloid plaques Phase III VTVT: $237.8M BACE - AZD3293 • To slow down AD by preventing amyloid beta buildup • Early AD • Eliminate amyloid plaques Phase II
Slide 14: Fragile X Syndrome - Orphan Drug
Fragile X Syndrome - Orphan Drug ; Most common single gene cause of intellectual disability ; Part of autism spectrum ; ~135,000 patients in U.S. ; Preclinical cognitive, behavioral, cellular studies performed at BRNI ; Preclinical additional behavioral studies performed at University of Santiago de
Slide 15: Niemann-Pick Type C Disease (NPC) - Orphan Drug
Niemann - Pick Type C Disease (NPC) – Orphan Drug ; Lysosomal storage disorder primarily affecting children ; Often causes death within the first two decades of life ; Originates from a gene defect that results in the inability to transport lipids within and between cells ; NTRP signed exclusive lic
Slide 16: World-Class Scientific Collaborations
World - Class Scientific Collaborations 16
Slide 17: Leadership Team
Leadership Team □ Charles S. Ramat – President, Chief Executive Officer and Board member □ Extensive operational and general business experience in both public and private companies □ Founding investor in Neurotrope □ Track record of increasing shareholder value at micro - and small - cap companies
Slide 18: Leadership Team (cont.)
Leadership Team (cont.) □ Dr. Daniel Alkon – Chief Scientific Officer □ Graduate of Cornell Medical School □ Mt. Sinai Hospital (NY) Internship in Medicine □ 30 year career as Medical Director and Lab Chief in US NIH specializing in memory disorders □ 14 years as founding Scientific Director of BRNI
Slide 19: AD Clinical Advisory Board
AD Clinical Advisory Board □ Dr . Jeffrey L. Cummings , MD, ScD, CCF - Chairman □ Director of Cleveland Clinic Lou Ruvo Center for Brain Health □ Professor of Neurology and Psychiatry, Director of MSE Center for AD Research and Director of the DFJ Center for Neurotherapeutics at UCLA □ Expert in cli
Slide 20: AD Clinical Advisory Board (cont.)
AD Clinical Advisory Board (cont.) □ Dr. Cristina Sampaio , MD, PhD □ Chief Clinical Officer at CHDI Foundation □ Professor of Clinical Pharmacology and Therapeutics University of Lisbon, Portugal □ Former member of the Committee of Proprietary Medicinal Products and the Scientific Advice Working Pa
Slide 21: Current Capitalization
21 Current Capitalization Shares Common Stock 49.2 MM Series B Convertible Preferred Stock (Convertible @ $0.60 / share)* 26.2 MM Total fully diluted shares 75.4 MM Trading Information Ticker symbol NTRP Share price (2/15/16) $0.41 Trading and Capitalization *: May automatically convert following a
Slide 22: Key Takeaways
Key Takeaways 22 ; Late - stage biotech with Bryostatin - 1, a novel compound for Alzheimer’s Disease – Lead compound in PKC Activator Platform ; New paradigm - p rimary focus is synaptogenesis through PKC ϵ activation while also inhibiting Amyloid Plaque and Tau ; Leveraging >$200 million R&D inves
Slide 23: Appendix
| Appendix Neurotrope BioScience
Slide 24: Bryostatin Mechanism of Action
Bryostatin Mechanism of Action ; Activates Synaptic Growth Factors – BDNF, NGF, IGF, others ; Activates All amyloid - β Degrading Enzymes (ECE, Neprilysin, IDE) ; Activates α - secretase, which reduces formation of neurotoxic amyloid - β formed by γ - secretase and BACE ; A poE3 induces PKC ϵ ; by a
Slide 25: Causes and Consequences of Neurodegeneration
Causes and Consequences of Neurodegeneration 25 ; Numerous elements influence the causes of Alzheimer’s Disease (AD): ; Causal Genes (PS1, PS2): 5% cases ; Risk Genes (ApoE4): 35% cases ; Age: >50% cases ; Two Chief Pathologic Consequences resulting of AD: ; Synaptic Loss ; Neuronal Loss Bryostatin
Slide 26: Therapeutic effects of PKC ε activation on AD
Therapeutic effects of PKC ϵ activation on AD 26 ; ApoE 4: Predominant genetic risk factor for AD ; Bryostatin blocks ApoE 4 via regulation of epigenetic factors, HDACs, and resulting stimulation of PKC ϵ expression, BDNF synthesis, and synaptogenesis ; PKC ϵ deficits observed in AD brains at Autops
Slide 27: PKC and Alzheimer's Disease
PKC and Alzheimer’s Disease Mouse model demonstrated reduced PKC in AD brain; increased PKC following b ryostatin treatment 27
Slide 28: BDNF Mechanistic Pathway
BDNF Mechanistic Pathway 28
Slide 29: Upregulation of BDNF
Upregulation of BDNF Treatment with bryostatin increased BDNF expression in AD transgenic mice 29
Slide 30: Improved Synaptic Function
Improved Synaptic F unction Treatment with bryostatin increased total dendritic spine count in AD transgenic mice – Improving synaptic function 30
Slide 31: Increase in Synaptogenesis
Increase in Synaptogenesis Treatment with bryostatin restored total synapses in AD transgenic mice 31
Slide 32: Enhanced Memory and Learning Ability
Enhanced Memory and Learning Ability 32 Treatment with bryostatin improved memory and learning in brown Norway rats via synaptogenesis Jarin Hongpaisan, and Daniel L. Alkon PNAS 2007;104:19571 - 19576
Slide 33: Enhanced Memory and Learning Ability
Enhanced Memory and Learning Ability 33 0 20 40 60 80 100 Escape latency (s) C+Vehicle Tg+BryTG+Vehicle 1st Trial Day 1 2 3 4 5 6 C+Bry Treatment with bryostatin improved memory and learning in 5X FAD transgenic mice 0 1 2 3 Target Quadrant Ratio N C+ Tg + Tg + C+ * * Learning Memory
Slide 34: Fragile X Mouse Model
Fragile X Mouse Model Treatment with bryostatin for 13 weeks beginning at two months ; Biochemical and morphologic effects at the synaptic level ; Improved synaptic function ; Synaptic maturation ; Increased synapse formation Synaptic - level effects resulted in improved cognition 34
Slide 35: Fragile X Mouse Model
Fragile X Mouse Model Treatment with bryostatin in FXS mouse restored synapses, improved memory & learning 35