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NEUROTROPE, INC.(Symbol: NTRP)
Improving the lives of patients with Cognitive and Neurodevelopmental disorders
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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 from those set forth in the
forward-looking statements.
Any statements that are not statements of historical fact (including statements containing the words
“believes,” “plans,” “anticipates,” “expects,” “estimates” and similar expressions) should also be considered
to be forward-looking statements. There are a number of important factors that could cause actual results or
events to differ materially from those indicated by such forward-looking statements. These factors are
contained in Neurotrope Inc.’s filings with the SEC, including Neurotrope’s Form 10-K for December 31, 2014
and Form S-1 filed on December 1, 2014. We encourage all viewers of this presentation to review the
aforementioned filings.
THESE MATERIALS DO NOT CONSTITUTE AN OFFER TO SELL, OR THE SOLICITATION OF ANY OFFER TO BUY, ANY SECURITIES OF THE COMPANY OR ANY ENTITY WHATSOEVER. ANY SUCH OFFER MAY ONLY BE MADE BY A PRIVATE PLACEMENT MEMORANDUM OR PROSPECTUS ISSUED BY THE COMPANY. ANY REPRESENTATION TO THE CONTRARY BY ANY PARTY SHOULD BE IGNORED.
The full text of Neurotrope’s SEC filings can be found at the SEC’s website
(http://www.sec.gov)
Safe Harbor Statement
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Overview
Bryostatin lead compound Novel mechanism for treatment of cognitive and
neurodevelopmental disorders Protein Kinase C (PKC) activator enhancing memory and
learning Extensive safety data from approx. 1,500 patients from
NCI trials Active programs in Alzheimer’s disease, Fragile X
Syndrome (FXS) and Niemann-Pick Type C disease (NPC) Successfully completed phase 2a Alzheimer’s disease
safety trial Proof of Concept phase 2b trial for Alzheimer’s disease
approved by FDA 150 patients study in moderately severe to severe
Alzheimer’s disease Granted Orphan Drug Designation by FDA for FXS Ongoing preclinical development for NPC.
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History
Neurotrope funded in 2013 ($23 million raised) to license the patent portfolio, from the Blanchette Rockefeller Neuroscience Institute (BRNI), for clinical development of Bryostatin
By date of NTRP funding, over $200 million invested in research & development by the National Cancer Institute (NCI) and BRNI
Technology involves activation and up regulation of PKC Extensive publications in peer reviewed journals Bryostatin used for Alzheimer’s disease treatment in FDA-
approved Compassionate Use cases Phase 2a Alzheimer’s disease clinical trial completed in Q4 2014 Letter of intent signed with Worldwide Clinical Trials to
commence Phase 2b proof of concept trial Q2 2015 Received FDA Orphan Drug Designation for Fragile X syndrome
Q1 2015.
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Bryostatin – Lead Compound
Bryostatin is derived from a marine organism, Bugula Neritina
Bryostatin potent activator of PKC Promotes synaptic function and synaptogenesis Inhibits neuronal cell death
NCI has significant bryostatin supply and through BRNI has supplied NTRP NTRP has sufficient amounts for upcoming Phase 2b
trial In conjunction with Stanford Univ. and Dr. Paul
Wender, bryostatin is being synthesized for commercial use.
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Scientific Rationale
PKC is known to play a pivotal role in learning and memory Bryostatin is a small molecule, penetrates blood-brain
barrier and activates PKC which: Increases brain-derived neurotropic factor (BDNF) Improves synaptic function Promotes new synapse formation Matures immature synapses Activates enzymes which alters amyloid metabolism and
activates three degradation pathways Activates Anti-apoptotic pathways
In NPC activation of PKC results in phosphorylation of a transport protein resulting in transport of lipids within and out of affected cells.
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Alzheimer’s disease
Preclinical work at BRNI demonstrated improved memory and learning in two different AD mouse models
Clinical Work FDA approved several Compassionate Use protocols in severe
AD patients Three patients treated, current patient treated for
approximately one year Significant improvement in cognition and activities of daily
living over treatment period Phase 2a clinical trial completed
Bryostatin appeared safe and well tolerated Demonstrated activation of PKC target
Phase 2b proof of concept trial – activities initiated.
PKC and Alzheimer’s Disease
Mouse model demonstrating reduction of PKC in AD brain and increase of PKC following bryostatin
treatment.
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Brain Derived Neurotropic Factor
Treatment with bryostatin increases BDNF expression in AD transgenic
mice.
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Improving Synaptic Function
Treatment with bryostatin increases total dendritic spine count in AD transgenic mice
– Improving synaptic function.
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PKC Activation and Learning13
Treatment with bryostatin improves memory and learning in Tg2576 AD
transgenic mice.
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PKC Activation and Learning
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60
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Esc
ape
late
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(s)
C+Vehicle Tg+BryTG+Vehicle
1st TrialDay 1 2 3 4 5 6
C+Bry
Treatment with bryostatin improves memory and learning in 5X FAD transgenic
mice.
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2
3
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ua
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C+Ve-
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Tg+Ve-
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Learning Memory
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Phase 2b Clinical Trial Design 150 moderately severe to severe AD patients
First patient enrolled planned for summer of 2015 Primary efficacy endpoint based on Severe Impairment Battery
Scale (SIB) Secondary efficacy endpoints – Activities of Daily Living (ADL),
Neuropsychiatric Inventory (NPI) and MMSE Three dosing levels of bryostatin vs. placebo Initial dose three months then crossover for three months First three month data targeted 2H 2016 Six month data targeted 1H 2017 World Wide Clinical Trials chosen as CRO
30 sites planned in U.S.
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Orphan Drug Program – Fragile X Most common single gene cause of
intellectual disability Part of autism spectrum
~135,000 patients in U.S. Preclinical cognitive studies performed at
BRNI Orphan Drug Designation granted Q1
2015 Clinical trial planned to begin Q4 2015.
Fragile X Mouse Model
Treatment with bryostatin for 13 weeks beginning at two months
Biochemical and morphologic effects at the synaptic level that improves synaptic function, matures synapses and increases synapse formation - all resulting in improved cognition.
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Fragile X Mouse Model
Treatment with bryostatin in FX mouse results in restoration of synapses and
improved memory & learning.
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Orphan Drug Program -Niemann Pick Type C disease
NPC is a lysosomal storage disease affecting mostly 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 licensing agreement with Mt. Sinai
School of Medicine (NY) for the work of Dr. Yiannis Ioannou, an expert in NPC, for use of bryostatin in NPC Dr. Ioannou has shown bryostatin can correct the lipid transport
defect in NPC cell lines NTRP and Mt. Sinai currently investigating bryostatin in NPC
mouse model NTRP goal is to initiate human trials before the end of
2016 based on successful animal experiments.
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Timeline
Q1 2015 Phase 2a clinical trial AD safety study - COMPLETE Orphan drug designation for Fragile X – GRANTED Enroll additional Compassionate Use patients -
ONGOING
Q2 2015 Initiation of Phase 2b Proof of Concept study for
moderately severe to severe Alzheimer’s patients, FDA approves study
LOI with Worldwide Clinical Trials – SIGNED Tripartite agreement for Fragile X with NTRP, FRAXA
and U of Santiago –SIGNED
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Timeline
Q3 2015 First patient enrolled in Phase 2b clinical trial
Develop clinical strategy for Fragile X with regulatory agency
Q4 2015 Fragile X Phase 2 PK and safety study initiated.
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Scientific Collaborations
Alzheimer’s Disease and Bryostatin Blanchette Rockefeller Neuroscience
Institute Stanford University
Synthetic development of bryostatin Bryolog development
Marinus Scientific Harvesting and extraction of natural bryostatin
Clinical Advisory Board (slides follows)
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Scientific Collaborations (cont.) Fragile X Syndrome
Blanchette Rockefeller Neuroscience Institute Preclinical cognitive studies
FRAXA Research Foundation University of Chile in Santiago/preclinical
behavioral studies Clinical Advisory Board
Rush University Medical Center-Chicago, Seattle Children’s Hospital Cincinnati Children’s Hospital Medical Center
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Scientific Collaborations (cont.) Niemann-Pick Type C
Icahn School of Medicine at Mount Sinai (NYC) Preclinical in-vitro and in-vivo studies
Albert Einstein School of Medicine (NYC) Preclinical in-vivo studies, CNS pathology
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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 clinical trial design & analysis, global trial implementation, outcome
measures Authored or edited 30 books and published 600 peer-reviewed papers Past President of Behavioral Neurology Society & American Neuropsych. Association.
Dr. Martin R. Farlow, MD Professor and Vice Chairman of Research, Dept. of Neurology Indiana University Associate Co-Director of the Indiana AD Center and member of gov’t. AD task force Principal Investigator of the Indiana site of the AD Cooperative Study Unit Published 200 peer-reviewed papers.
Dr. Samuel E. Gandy, MD, PhD Mount Sinai Chair in AD Research, Professor of Neurology and Psychiatry at Mount
Sinai Director of the Mount Sinai Center for Cognitive Health and NFL Neurological Care Former Chairman of the National Medical & Scientific Advisory Council of the AD
Association Founding Director of the Farber Institute of Neurosciences, Jefferson Medical College Discovered PKC regulation of amyloid precursor phosphorylation and processing.
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Clinical Advisory Board (cont.) Dr. Cristina Sampaio, MD, PhD
Chief Medical 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 Party at the European Medicines Agency.
Dr. Michael Weiner, MD Professor UCSF School of Medicine in Radiology and Biomedical
Imaging Principle Investigator of the AD Neuroimaging Initiative Educated at Mount Sinai and Yale, previously Assistant Professor of
Medicine at Stanford Established the MR Unit at the San Francisco VA Medical Center.
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Leadership Team
Charles S. Ramat – President, Chief Executive Officer and Board member Extensive operational and general business experience
in both public and private companies Industry focus - Biotechnology, medical devices,
commercial finance, real estate
Paul Freiman – Chairman of the Board Seasoned pharmaceutical executive Former Chairman and CEO Syntex – Sold to Roche for $5
billion+ Board member NovaBay Pharmaceutical (NYSE: NBY) Chairman Chronix BioMedical.
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Leadership Team (cont.)
Dr. Dan Alkon – Chief Scientific Officer Graduate of Cornell Medical School 30 year career as Medical Director and Lab Chief in US NIH
specializing in memory disorders 14 years as founding Scientific Director of BRNI
Dr. Warren W. Wasiewski – Chief Medical Officer Board certified in Neurology and Pediatrics Over 30 years of medical and pharmaceutical experience Extensive clinical & regulatory experience in Neurology, Pediatrics
and Orphan disease space at AstraZeneca, InfaCare and Alexion
Robert Weinstein, CPA, MBA – Chief Financial Officer Experienced healthcare industry CFO and consultant Successful healthcare private equity fund manager & investment
banker.
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Current Capitalization Shares
Common Stock 27.6 MM
Series A Convertible Preferred Stock (Convertible @ $1.00 / share) 18.0 MM
Options & Warrants Outstanding (Weighted Avg. E.P. $1.39 / share) 9.0 MM
Total fully diluted shares 54.6 MM
Trading Information
Ticker symbol NTRP
Current share price (5/19/15) $0.96
Capital raised during 2013 $23 million
Cash as of May14, 2015 $4.5 million
Trading and Capitalization