Paradigm Shift in the Treatment of Alzheimer’s

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NEUROTROPE, INC. (OTCQB: NTRP)

February 2017

Safe Safe HarborHarbor StatementStatement

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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  materially  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 Annual Report on Form 10-K for  the year ended December 31, 2015 and its Quarterly Report on Form 10-Q for the quarter ended September 30, 2016  and registration  statement on Form S-1  filed on January 14, 2016. We encourage all viewers of  this presentation  to  review  the   aforementioned  filings.  All  statements  contained  in  this  presentation  are  made  only  as  of  the  date  of  this presentation,  and we do not undertake any obligation  to publicly update any  forward  looking statements.

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)

The Neurotrope Difference: Paradigm Shifting Science The Neurotrope Difference: Paradigm Shifting Science In The Treatment of Alzheimer’s In The Treatment of Alzheimer’s

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Clinical-stage biopharmaceutical company developing novel therapies for neuro-degenerative diseases, initially focused on Alzheimer’s

Fundamentally novel understanding on the causes of Alzheimer’s

Focus re-generation of synapses and synaptic networks rather than neuronal loss through beta amyloid plaque and tau tangles

Potential to reverse Alzheimer’s even in advanced patients –

Unique regenerative approach based on molecular understanding of memory and learning based on PKC epsilon activation

Mechanism of action fundamental to other neuro-degenerative disease

Platform technology, fundamental mechanism underlying a larger number of neuro-degenerative diseases (FXS, Rett Syndrome; stroke, TBI, depression)

The Neurotrope Difference: The Neurotrope Difference: Upcoming Phase 2 Data Upcoming Phase 2 Data

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Upcoming Phase 2 topline data in April 2017 in moderate to severe Alzheimer’s – pivotal valuation inflection point:

148 patients, double-blind, placebo-control, 26 sites US sites

Bryostatin, lead compound, well tolerated in 1500 patients

Extensive preclinical data, preliminary clinical and Compassionate Use data

Major Corporate DevelopmentsMajor Corporate Developments

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Neurotrope formed in 2012 out of the Blanchette Rockefeller Institute (BRNI) Dr. Alkon – 30 years at NIH; 15 years at BRNI > 300 publications > $200m funding while at NIH and BRNI > $35 million raised since NTRP inception (2012- 2015)

Major restructuring in August/ September 2016 Closed an additional $24.3 million (Nov 2016) Restructured Board & Management Change Dr. Alkon joined as President in addition to CSO

Dynamic Clinical Program Development, next 12 – 18 months Alzheimer’s disease (AD) program Fragile X Syndrome Program (FXS)

January 2017 announces plans to list on NASDAQ and Neurotrope Completes Licensing Agreement for Accelerated

Synthesis of Alzheimer’s Drug Bryostatin-1 

LeadershipLeadership TeamTeam

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Dr. Susanne Wilke, Ph.D , MBA – Chief Executive OfficerSignificant sector, business development. commercial, and investing experience World-wide Director of Commercial Assessment/ In-licensing at Forest Labs

(now Allergan) Venture Capital Investor (SVLS, NGN Capital): - led > 17 investments, Previous leadership positions at Roche, Amgen, The Monitor Group Dual Ph.D, Bio-Chemistry/Drug Development; MBA-Tuck/ Dartmouth,

Kauffman Fellow

Dr. Daniel Alkon, MD – President, Chief Scientific Officer Specializing in memory and neuro-degenerative diseases 30 years at NIH, 15 years at the B.R.N.I > 300 peer reviewed publications Graduate of Cornell Medical School, Mt. Sinai

Dr. Kenneth Gorelick, MD – Interim Chief Medical Officer Managing Director of Zymo Consulting Group LLC Graduate of Cornell Medical School, Mt. Sinai

Robert Weinstein, CPA, MBA – Chief Financial Officer Experienced CFO, Private Equity and Investment Banking

Synaptic Loss – Not amyloid plaques Synaptic Loss – Not amyloid plaques and tangles - Correlates with AD and tangles - Correlates with AD

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Ann Neurol 1991

Molecular Understanding of Memory Molecular Understanding of Memory Key Insights – Molecular Understanding of Memory

Based on Electron/ Confocal Microscopy Studies

Synaptic networks are key to memory

Disruption of synaptic networks leads to cognitive loss, disease; regeneration of synaptic networks lead to memory enhancement > 11 animal models

PKC epsilon a key player in memory and neurodegenerative process. Activation of PKC e acts as a master switch in increase synaptogenesis

Identified Bryostatin, as a highly potent and selective activator of PKC epsilon in the brain

Harvard Study: Fresh Frozen Brain samples of AD patients showed PKC epsilon deficiency

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Dr. Alkon, MD – Pioneer in Memory Research

PKCe: PKCe: Master Master Switch Switch for for MemoryMemory, , DiseaseDisease

Activates Synaptic Growth Factors – BDNF, IGF- 1, NGF and others

Activates All amyloid-β Degrading Enzymes

Increases in BDNF via ApoE3 induced PKCϵ

Increases BDNF via loss of ApoE4 mitigated reduction of BDNF

Activates α-secretase reducing neurotoxic amyloid-β

Bryostatin normalizes GSK3-β, thereby inhibiting pathological Tau

Brain Health• Memory and Learning• Spatial Recognition

Decreased PKCe activation leads to reduced synaptic density

Reduced Synaptic Growth Factors – BDNF, IGF-1, NGF, others

Inactivated amyloid-β degrading enzymes increased neurotoxic amyloid-β

Increasing pathological Tau

Neurodegenerative Diseases:• Alzheimer’s• Fragile X (FXS)• Rett Syndrome• Stroke

Multi- modal effects

                NTRP 9

Multi-Modal Multi-Modal Mechanism Mechanism ofof ActionAction

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Acvation of Protein Kinase C epsilon (PKCϵ) Activates Synaptic Growth Factors – BDNF, NGF, IGF, others Activates All amyloid-β Degrading Enzymes (ECE, Neprilysin, IDE,

ect)

Activates α-secretase, which reduces formation of neurotoxic amyloid-β formed by γ-secretase and BACE

ApoE3 induces PKCϵ; by activating PKCϵ, there is an increase in BDNF expression

Bryostatin blocks ApoE4 reduction of BDNF via HDAC inhibition

Bryostatin normalizes GSK3-β, thereby inhibiting pathological Tau protein transformation into neurofibrillary tangles (NFTs)

Bryostatin targets multiple pathways

Snapshot of Bryostatin - Synaptogenesis Snapshot of Bryostatin - Synaptogenesis

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On The Cover: Integrative neurons in the hippocampus show large oval nuclei (blue) and presynaptic axonal boutons. Yellow grains, boutons with brain-derived neurotrophic factor (BDNF); green grains, boutons with no BDNF accumulation; red grains, postsynaptic dendritic spines with BDNF. BDNF is important for synaptic activity and neuron survival. The PKCε activator, bryostatin 1, enhanced the presence of the synaptogenic growth factor, BDNF, as indicated by the yellow dots. For details, see the JBC article by Sen et al., pages 16462–16476.

Pre-clinical Data:

Bryostatin Prevents the Loss of Synapses in AD-transgenic Mice (Tg2576)

Electron microscopy of the stratum radiatum in the hippocampal CA1 area. Red arrows point to all synapses and mushroom spines are highlighted in yellow. **p<.01, ***p<.001; two-tailed t-test. n=3 mice and n=25-35 electron micrographs in each group. Synapse loss was entirely prevented by Bryostatin treatment.

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Bryostatin Bryostatin - Clinical- Clinical DevelopmentDevelopment

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Safety and Clinical Development

Safety 1,500 patients in NCI – well tolerated

Compassionate Use protocols in severe AD patients

❒ Significant improvement in cognition and daily living

❒ Possibility of disease reversal

❒ Three patients treated, longest dosed patient ~followed for one year

• Phase 2a clinical trial completed❒ Bryostatin achieved primary safety endpoint

❒ Demonstrated activation of PKCϵ target engagement ❒ Cognitive enhancement within 3 hours

• Phase 2: last patient dosed , top-line efficacy data April 2017

Bryostatin Compassionate Use Program: Severe Alzheimer’s Disease No other reports have ever shown comparable benefits in such severely

demented patients – albeit in the absence of age-matched controls.

Patient 1 - 95 y/o ♂ (JT) – disoriented, intermittent coma, non-verbal

Course: Became alert, attentive; remembered date, place, time; mind active, engaged, watching TV, requested to return to work

Patient 2 - 38 y/o ♀ (JS) - familial Early-Onset AD due to PSEN1 mutation Non-verbal, drooling, unable to swallow (fed with gastrostomy), attention grossly impaired, spasticity, inability to move

Course: Return of some language and vocalization, swallowing, increased attentiveness to environment & persons, increased range of motion

Patient 3 - 76 y/o white (FC)

Course: MMSE: 2-3 improves to 10 -12; recognizes, vocalizes words

ADCS-ADL-sev score: 18 improves to 33; Hallucinations: reduced;

Return of complex motor skills – e.g. swimming, billiards

Compassionate Use Patients: Overview

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Phase 2 – Ongoing Clinical TrialPhase 2 – Ongoing Clinical Trial Double – Blind, Placebo – controlled, 148 moderate to severe AD patients dosed over 12 weeks

q Dosing initiated in January 2016, trial fully enrolled

q Full data results expected April 2017

qPrimary efficacy endpoint: ◦ Severe Impairment Battery (SIB) possible disease reversal

q Secondary efficacy endpoints: ◦ Mini-Mental State Exam (MMSE)◦ Activities of Daily Living (ADL)◦ Neuropsychiatric Inventory (NPI)

q 20ug and 40ug doses of bryostatin vs. placebo

q26 sites all in the U.S.

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Clock Drawing Test – MMSE 10 - 0

Current Neurotrope Current Neurotrope Phase 2Phase 2::MMSE: Secondary MMSE: Secondary Clinical Endpoints Clinical Endpoints and and

Screening Tool - Severe PatientsScreening Tool - Severe Patients

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Phase Phase 2 - 2 - Clinical AssessmentClinical Assessment MethodsMethods

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Cognition

Behavior

Function

Neuropsychiatric Inventory (NPI)

AD Cooperative  Study −Activities of Daily  Living, severe

(ADCS-ADL-SIV)Mini Mental  State  Examination  (MMSE)

Severe  Impairment  Battery  (SIB)

Neurotrope Neurotrope Phase 2:Phase 2:

Baseline Baseline Characteristics - EndpointsCharacteristics - Endpoints

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Mean sd Median Range AD-Type

Age 72.2 7.8 73 55 – 85

Gender M/F 49/55

MMSE (screened, N=212) 10.2 4.0 10.5 0 – 20

MMSE (randomized, N=125)* 10.0 3.5 11.0 4 – 15 Severe

<10

SIB (randomized) 76.4 19.1 83.0 11 – 99

NPI (randomized, Freq x Sev) 13.9 14.1 10.0 0 – 77

NPI (randomized, caregiver distress) 7.3 6.4 6.0 0 – 37

ADCS-ADL-SIV (randomized) 35.5 10.8 37.5 6 – 54

MMSE (Mini-Mental State Exam), SIB (Severe Impairment Battery); ADL (Activities of Daily Living); NPI – (Neuropsychiatric Inventory); * Sept. 21, 2016

Memantine Memantine –– Approved Approved IIn Moderate n Moderate –– Severe Patients - Results Severe Patients - Results

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Registration Trial: NEJM, 2003 : SIB (Severe Impairment Battery) - best correlating scale

Biogen (2016): Highest Dose Still Results in Decline in MMSE, No Reversal

Nature. 2016 Aug 31;537(7618):50-6. doi: 10.1038/nature19323.

Aducanumab effect (change from baseline) on MMSE.*P< 0.05 versus placeboThere was over a 30 percent rate of brain edema in Mild Cognitive Impairment patients

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World Class AD Clinical AdvisorsWorld Class AD Clinical Advisors

q Dr. Jeffrey L. Cummings, MD, ScD, CCF - Chairmanq Director of Cleveland Clinic Lou Ruvo Center for Brain Healthq Expert in clinical trial design & analysis, global trial implementation, outcome measuresq Authored or edited 30 books and published 600 peer-reviewed papers

q Dr. Martin R. Farlow, MDq Professor and Vice Chairman of Research, Dept. of Neurology Indiana Universityq Associate Co-Director of the Indiana AD Center and member of gov’t. AD task forceq Published 200 peer-reviewed papers

q Dr. Samuel E. Gandy, MD, PhDq Mount Sinai Chair in AD Research, Professor of Neurology and Psychiatry at Mount Sinaiq Discovered PKC regulation of amyloid precursor phosphorylation and processing

q Dr. Michael Weiner, MDq Professor UCSF School of Medicine in Radiology and Biomedical Imagingq Educated at Mount Sinai and Yale, Assistant Professor of Medicine at Stanfordq Established MRI Unit at the San Francisco VA Medical Center

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Fragile Fragile X X SyndromeSyndrome discussiondiscussion

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Most common inherited cause of mental retardation, genetic cause of autism and single gene cause of intellectual disability

• ~135,000 patients in U.S.• Affects 1 in 3000-4000 boys, 1 in 4000-8000 girls

Subtle physical phenotype with striking neuropsychiatric phenotype

25-30% of full-mutation males meet criteria for a dx of autism, nearly all the rest have Autism Spectrum Disorder/Pervasive Developmental Disorder

20-25% of males have seizures Normal life expectancy True developmental disorder---not neurodegenerative Treatments offer only symptomatic benefit

World World Class FXS ClinicalClass FXS Clinical AdvisorsAdvisors

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Chairperson : Elizabeth Berry-Kravis MD, PhD, Rush Medical

Randy Haberman, Mind Center, UCSD

Craig Erickson, MD, Chief NIH Clinical Advisory Group

Bryan King, MD, UCSF

Sara Jane Webb, MD, U. Washington

Mike Tranfaglia, MD, President of FRAXA

World-Class World-Class ScientificScientific CollaborationsCollaborations

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Trading and Capitalization Trading and Capitalization

Ticker Symbol NTRP

Share Price (02/10/17)$13.35

Common Stock 8 M

~5.7 million warrants $12.80 - $32 per share and .7 million options $10.56 - $71 per share Market Cap $107 M

Pro-rata Cash Balance as of 11/22/16 $30 M

:                 NTRP 26

Neurotrope AppendixNeurotrope Appendix

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A Multi-modal Strategy for Alzheimer’s Disease: A Multi-modal Strategy for Alzheimer’s Disease:

PKC PKC εε Activators Activators

Restore Lost Synapses - Synaptogenesis

Protect against Neuronal Loss - Anti-apoptosis

Treat Cognitive Deficits

Anti-Aβ Oligomers, Prevent Plaques

Anti- τ phosphorylation, Prevent Tangles

A2

Neurotrope Therapeutics for Neurodegeneration

I. Therapeutic Targets for Early, Late Alzheimer’s Disease (AD):

l. Synapse Regeneration 2. Prevention of Neuronal Death 3. Anti-Amyloid 4. Anti-tau

II. Potential Efficacies l. Underlying Disease – prevention, reduction,

reversal 2. Symptomatic Relief 3. Cognitive Enhancement

A3

ApoE - PKC ε : Mechanistic Relevance For Alzheimer’s Disease

• A poE 3: Increases Genetic Expression of PKC ε –  BDNF Synaptogenesis -   Activated by Bryostatin

• ApoE 4: Genetic Risk Factor for AD - Prevents PKC ε - Synaptogenesis -   Blocked by Bryostatin

• PKC ε Degrades A Beta Oligomers, Activates alpha secetase

• PKC ε Deficits in AD Brains at Autopsy (Harvard/BRNI)

• PKC ε Enhances/Mediates Learning and Memory

A4

Snapshot of Bryostatin - Synaptogenesis Snapshot of Bryostatin - Synaptogenesis

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On The Cover: Integrative neurons in the hippocampus show large oval nuclei (blue) and presynaptic axonal boutons. Yellow grains, boutons with brain-derived neurotrophic factor (BDNF); green grains, boutons with no BDNF accumulation; red grains, postsynaptic dendritic spines with BDNF. BDNF is important for synaptic activity and neuron survival. The PKCε activator, bryostatin 1, enhanced the presence of the synaptogenic growth factor, BDNF, as indicated by the yellow dots. For details, see the JBC article by Sen et al., pages 16462–16476.

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cc400 nm

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Maze+BryoMaze+Bryo

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Macular PSDMacular PSD

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Learning Specifically increases:

the number of mushroom spine

synapses

Water maze training - Electron MicroscopyA6

Bryostatin-1 Preserves Synapses (CA1 Neurons)

in Tg2576 AD Transgenic mice

A7

Bryostatin prevents the loss of synapses in AD-transgenic mice (Tg2576)

Electron microscopy of the stratum radiatum in the hippocampal CA1 area. Red arrows point to all synapses and mushroom spines are highlighted in yellow. **p<.01, ***p<.001; two-tailed t-test. n=3 mice and n=25-35 electron micrographs in each group. Synapse loss was entirely prevented by Bryostatin treatment

A8

Prevent Loss of Learning & Memory

In 5XFAD Mice: - Bryostatin-1 or - PKCε activator

Bryostatin-1 at 20 g/m2 (tail i.v., 2 doses/week for 9 weeks); water maze: 3 trials/day

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PKCε

Aβ

-

--

-

Amyloid/PKC Metabolism

Progression Targets

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Tau/PKC Metabolism

Progression Targets

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PKC-ε Activator reduces the formation of amyloid plaques in AD-transgenic mice (5X FAD)

Wild 5X FAD5X FAD+

PKC activator

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A12

Cerebral ischemic rats: anti-apoptosis – Bryostatin

Bryostatin-1 (15 g/kg. iv; 2 doses/ week for 5 weeks) A13

Bryostatin Background

• Purified from marine bryozoan Bugula neritina

• Potent activator of PKC ε

• Reached phase II clinical trials as an anti-tumor agent (metastatic melanoma), but was ineffective

• Well-tolerated at Doses for Neurodegeneration

• Phase II a Trial Safety, Initial Pharmacokinetics (NTRP)

• Phase II b FDA Recently Approved 150 patient trial (NTRP)

Compassionate Use Trials (NTRP) – efficacy in Severe AD A14

Bryostatin Compassionate Use Program: Severe Alzheimer’s Disease No other reports have ever shown comparable benefits in such severely demented patients – albeit in the absence of age-matched controls.

Patient 1 - 95 y/o ♂ (JT) – disoriented, intermittent coma, non-verbal

Course: Became alert, attentive; remembered date, place, time; mind active, engaged, watching TV, requested to return to work

Patient 2 - 38 y/o ♀ (JS) - familial Early-Onset AD due to PSEN1 mutation Non-verbal, drooling, unable to swallow (fed with gastrostomy), attention grossly impaired, spasticity, inability to move

Course: Return of some language and vocalization, swallowing, increased attentiveness to environment & persons, increased range of motion

Patient 3 - 76 y/o white (FC)

Course: MMSE: 2-3 improves to 10 -12; recognizes, vocalizes words

ADCS-ADL-sev score: 18 improves to 33; Hallucinations: reduced;

Return of complex motor skills – e.g. swimming, billiards

A15

Orphan Drugs: Bryostatin Normalizes Fragile X Synapses

A16

Alzheimer’s Disease – early, moderate, severe

Fragile X Disease – Orphan Drug Status

Stroke

Traumatic Brain Injury

Mood Disorders

Niemann-Pick Disease

Potential Indications

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