Cyclo Therapeutics (OTCQB: CTDH) is a clinical-stage biotechnology company that develops cyclodextrin-based products for the treatment of disease. The Company’s Trappsol® Cyclo™, an orphan drug designated product in the United States and Europe, is used to treat Niemann-Pick Disease Type C (NPC), a rare and fatal genetic disease, on a compassionate use basis as well as in three ongoing formal clinical trials. The Company’s Scientific Advisory Board endorsed Alzheimer’s Disease (AD) as the company’s next drug development indication. The Company was authorized by the FDA to use Trappsol® Cyclo™ for a late-onset AD patient under a Compassionate Use Program which began intravenous dosing in May 2018. Learn more at CTDHinfo.com.

1. 1
OTCQB: CTDH

2. Safe Harbor Statement
2
Some of the information in this report relates to future events or future business and financial performance. Such statements
constitute forward-looking information within the meaning of the Private Securities Litigation Act of 1995. Such statements can
be only predictions and the actual events or results may differ from those discussed due to, among other things, the risks
described in the public filings and other publications of Cyclo Therapeutics, Inc. Forward-looking statements are identified by
words such as “anticipates”, “projects”, “expects”, “plans”, “intends”, “believes”, “estimates”, “target”, and other similar
expressions that indicate trends and future events.
The content of this report with respect to Cyclo Therapeutics, Inc. has been completed primarily from information available in
the public released by Cyclo Therapeutics, Inc. through news releases and SEC filings. Cyclo Therapeutics, Inc. uses data
from publicly available information and its accuracy has not been independently verified by Cyclo Therapeutics, Inc. Certain
summaries of scientific activities and outcomes have been condensed to aid the reader in gaining general understanding.
The information about Cyclo Therapeutics, Inc. and its subsidiaries is solely for information purposes and is not to be
construed as an offer to sell or the solicitation of an offer to buy any security in any state.
Factors that could cause the Company’s results to differ materially from those expressed in forward looking statements include
without limitation, variation in demand and the acceptance of the Company’s products and services, the frequency, magnitude
and timing of raw material price changes, general business and economic conditions beyond the Company’s control, the
consequences of competitive factors in the market place including the ability to attract and retain customers, and the
Company’s success in attracting and retaining key personnel.
Past performance does not guarantee future performance. This report is not to be copied, transmitted, displayed, distributed
(for compensation or otherwise), or altered in any way without the prior written consent of Cyclo Therapeutics, Inc.

3. Company Overview
• Corporate headquarters in Gainesville, FL
• Founded in 1990 as a cyclodextrin-distribution company
• Game changer: Dr. Benny Liu showed in 2006 that one version of cyclodextrins, hydroxypropyl beta
cyclodextrins, can release cholesterol from cells in animal models of Niemann-Pick Disease Type C (NPC).
NPC is a rare inherited neurodegenerative disease that affects infants, children and adults. It is caused by
an accumulation of lipids in the liver, brain and spleen.
• This discovery led directly to CTD providing cyclodextrins to NPC families for use in compassionate
programs. Dr. Hastings was first to administer our product to NPC patients, route of administration was
Intravenous.
• This led directly to ground-breaking work of other physicians in the US, Brazil and other countries, then
ultimately to our decision to develop our version of hydroxypropyl beta cyclodextrin, Trappsol® Cyclo™, as
a treatment for Niemann-Pick Disease Type C.
3
Cyclo Therapeutics, a clinical-stage biotechnology company, is developing
cyclodextrin-based products for the treatment of diseases with unmet
medical need

4. • Phase II in Europe/Israel and Phase I in U.S. - recruiting, dosing in Niemann
Pick Disease Type C (NPC)
• NPC and AD, Compassionate Use Program ongoing in multiple countries
• Granted Orphan Drug Designation (ODD) by the U.S. Food and Drug
Administration and European Medicines Agency; Rare Pediatric Disease
Designation (U.S.) and Fast Track designation (U.S.)
• Alzheimer's Disease moving towards Phase I
• NPC represents significant $500mm+ annual addressable market
• Alzheimer’s Disease $1 Billion+ Opportunity
Approximately $10 million invested by insiders
• Recently closed $7.4M institutional equity financing.
• Cyclodextrins are modifiable for multiple therapeutic areas
• Company is leader in Intravenous use of cyclodextrins
• ODD gives market exclusivity for 7- 12 years
• The company holds trademark, copyright and trade secret intellectual
property around the Trappsol® Cyclo™ product.
Investment Highlights
Trappsol®
Cyclo™
Active clinical programs in
Niemann Pick Disease and
Alzheimer's Disease
Large Market
Opportunity
Strong Management
Team & Board
Robust
Cyclodextrin
Portfolio & IP
4
Strong Balance
Sheet

5. Trappsol® Cyclo™
• Trappsol ® Cyclo ™ is CTD’s proprietary formulation of hydroxypropyl betacyclodextrin.
• HPβCD = 7 glucose molecules in a ring, modified by adding propyl groups, to enhance solubility. The inner
core of HPBCDs can make complexes with cholesterol and other molecules.
• HPβCDs widely used as excipient in products including Sporanox (broad-spectrum anti-fungal), eye drops,
and mouthwash.
5
Figure is courtesy of David Begley, Kings College
This schematic represents interaction of cylinder shaped
cyclodextrins and cholesterol in a 1:1 or 1:2 ratio
β-Cyclodextrin, R=H
HPβCD, R=OCH2CH(CH3)OH or H

6. Niemann-Pick Disease Type C:
Overview
6
An autosomal recessive lysosomal
storage disease
1/80,000 - 1/120,000
Live Birth Incidences
The disease is associated
with accumulation of
cholesterol in late
endosomes and
lysosomes due to loss of
normal function of the
NPC protein (NPC1 in
95% of cases, NPC2 in
5% of cases).
NPC damage can be
found in the brain, liver,
and other body tissues.
Depending on severity of
the disease, cognitive
impairment, movement
disorders, swallowing,
lung, liver and other
normal functions are
affected.
NPC is highly variable,
presenting usually in
young children, who often
do not survive into
adulthood, and also has a
later onset presentation
which leads to longer
term disability. The
disease is difficult to
diagnose and, therefore,
under-diagnosed.

7. Niemann-Pick Disease Type C:
Market Potential
7
Existing NPC
Cases
Number of
live births
Incidence
New Cases /
Year
Annual
Diagnosis
Rate
Patient
Penetration
Treatable
Cases/Year
Annual IV
Orphan Drug
Price (Avg.)
3,000* 137,000,000 **1/100,000 1,370 25% 50% 171 $404,737***
* Extrapolation from BMC Neurol. Dec 15,15(1):257) and other assumptions **Wassif, C et al. Genet Med. 2016 January ; 18 (1):41-48***LifeSci Capital.,
“Analysis of Orphan Drug Market”. Feb 4, 2016,
• Addressable market approaching $500mm
• Diagnosis capacity is improving – numbers of patients seeking treatment will increase

8. Compassionate Use Program with
Intravenous Trappsol® Cyclo™
8
Clinical data have allowed treating physicians to continue to use
HP-β-CD compassionately for more than 10 years in some cases.
IV Trappsol® Cyclo™ has been
administered to > 20 NPC patients
worldwide
Individual patients exhibit objective
Systemic/CNS responses
• Favorable tolerability profile among
patients treated to date.
• Safety profile has enabled physicians to
continue treatment > 6 years.
• Reduction in hepatic volume and
improvement in transaminases.
• Restoration of language skills.
• Resolution of interstitial lung disease.
• Improvement in fine and gross motor
skills.
• Improvement in quality of life.

9. Trappsol® Cyclo™ Phase I Study to Evaluate
Safety and Impact On Biomarkers of NPC Disease
• Niemann-Pick Disease Type C
- Confirmed diagnosis of NPC – 1
- NIH NPC Severity Score <30 and with no
more then 4 individual domains with a score of
> 3
- Age range: 18 years upwards
• Total Sites: 2 in United States
- Emmes is supporting the study with site
management and monitoring
- UCSF Benioff Children’s Hospital Oakland, CA;
and, Morristown Medical Center, Morristown, NJ
• Trial Timeline
- First patient enrollment: Q’3 17
- First patient dosed Q’3 17
9
United
States
Randomization 6:6 Between Dose Groups
Trappsol® Cyclo™: Bi-weekly 8 hour intravenous
treatment for a period of 14 weeks
RANDOMIZE (N=12)
Dose Group 1
1500 mg/kg
Dose Group 2
2500 mg/kg
Primary
Endpoint
• Plasma levels of Trappsol® Cyclo™
Secondary
Endpoint
• Markers of Cholesterol
metabolism/synthesis
• CSF Levels of Trappsol® Cyclo™
• hepatic and splenic morphology
• global impression of disease
Exploratory
Endpoint
• CSF biomarkers of NPC Disease

10. Trappsol® Cyclo™
Phase I/II Study to Evaluate Safety and Efficacy
10
Europe
Randomization 4:4:4 Between Dose Groups
Trappsol® Cyclo™: Bi-weekly 8 hour intravenous
treatment for a period of 48 weeks
RANDOMIZE (N=12)
Dose Group 2
2000 mg/kg
Dose Group 1
1500 mg/kg
Dose Group 3
2500 mg/kg
Primary
Endpoint
• Plasma levels of Trappsol® Cyclo™
Secondary
Endpoint
• Markers of Cholesterol
metabolism/synthesis
• CSF Levels of Trappsol® Cyclo™
• Clinical Outcomes (motor Skills,
cognition, eye movements, liver
morphology et al)
• global impression of disease
Exploratory
Endpoint
• CSF biomarkers of NPC Disease
• Niemann-Pick Disease Type C
- Confirmed diagnosis of NPC – 1
- NIH NPC Severity Score <30 and with no
more then 4 individual domains with a score of
> 3
- Age range: 2 years upwards
• Total Sites: 5-6 in 4 Countries
- UK, Sweden, Italy, Israel
- Aptus/Synteract is supporting the trial with site
management and monitoring
• Trial Timeline
- First patient enrollment: Q’2 17
- First patient dosed Q’3 17

11. Initial Data from U.S. and E.U./Israel trials
• Safety data show positive profile.
• Trappsol® Cyclo™ releases cholesterol from cells of NPC patients, allowing for cells
to normalize.
• Trappsol® Cyclo™ crosses the blood-brain-barrier following IV administration.
• One marker for NPC disease severity, lysosphingomyelin-509, shows a downward
trend with successive administration of IV Trappsol® Cyclo™. Another biomarker of
neurodegeneration, tau, trends downward in the cerebrospinal fluid. This tells us
that as Trappsol ® Cyclo™ clears cholesterol from cells, there are downstream
effects on markers of NPC disease severity.
• Clinical efficacy data are limited but encouraging. Disease specific features,
including fine motor, gait, and cognition improve in some subjects. Most patients for
which data are available either stabilized or improved in disease specific features.
11

12. Milestones – Niemann Pick trials
• Phase I trial – completing enrollment
• Phase I/II trial – completing enrollment
• Unblind dosing data from US and Europe/Israel NPC trials and correlate
biochemical and morphological changes with clinical outcomes. Timing under
discussion with regulators.
• Design of global pivotal trial -- Underway
• Meetings with Regulators to discuss pathway to approval – Upcoming
12

13. NPC and Alzheimer’s Disease share common features:
• Neurofibrillary tangles, tau, amyloid beta plaques in brains of NPC and AD patients
• Hypercholesterolemia is a risk factor for AD
• Lysosomal dysfunction found in both NPC and AD
• Increased cellular cholesterol increases the association of an enzyme, secretase, with
the precursor protein to amyloid beta (APP), leading to increased levels of amyloid beta
Cell and Animal models for AD studies using HPBCDs show:
• HPBCDs added to cells that over-express the precursor protein APP lowers amyloid beta
• HPBCDs given subcutaneously to a mouse that over-expresses APP:
• reduces amyloid beta by reducing cleavage of APP;
• improves memory as shown in a standard water maze test;
• reduces microgliosis;
• up-regulates genes involved in cholesterol transport and amyloid beta clearance
(as well as NPC1)
13
Links between NPC and Alzheimer’s Disease
Reference: J. Yao, et al. Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease. J. Exp. Med. 2012, V. 209 (13):
2501-2513

14. Alzheimer’s Disease
Compassionate Use Program
• Individual IND authorized by FDA to use Trappsol® Cyclo™ in late-onset Alzheimer’s
patient
• PI is award-winning, highly recognized Alzheimer’s expert, Diana Kerwin MD
• President of Kerwin Research Center, Dallas Texas
• Formerly oversaw clinical trials and research for the National Institute on Aging-funded
Cognitive Neurology and Alzheimer’s Disease Center at Northwestern University,
Chicago
• Program costs funded 100% by external organization with CTD providing clinical manuals
and other clinical materials, validation methodologies for biomarker analyses, and expert
input on protocol design
• Intravenous Dosing of Alzheimer’s patient began in May 2018
• FDA accepted annual report, positive safety profile, efficacy analysis ongoing, second year
of dosing commenced June 2019
14

15. Plan to Develop a HPBCD more able to cross blood-brain-barrier
• CTD has initiated planning with Professor David Begley, Kings College London, and Professor
Frances Platt, Oxford University, to design and test a novel HPBCD more able to cross BBB
• Takes advantage of receptors on endothelial cells of the BBB, natural transporters
• Chemically modify HPBCD to link a peptide that will bind to specific receptors, allowing
transport into the CSF/brain
• Potential delivery of other molecules in core of HPBCD
• Year 1 plan: create modified constructs, test in vitro to identify most effective
• Year 2 plan: test new construct(s) in animal models
15
In the R & D Pipeline
Target Peptide

16. IP & Patent Protection
• The Company has a validated, robust manufacturing process for Trappsol® Cyclo™ that includes
important trade secret steps and is proven to be scalable to commercial production.
• Trappsol® Cyclo™ has stability monitoring data to support a 48 month expiration date and will
soon be able to support 60 months.
• This includes in-use stability data for 48 hours following dispensing
• The Company holds valuable registered trademarks and copyrights including the Trappsol®
Cyclo™ brand name
• Type II Drug Master File (DMF)
• CTD filed a patent on “Methods for Treating Alzheimer’s Disease” with the U.S. Patent and
Trademark Office
• The filing describes dosing regimens and routes of administration of hydroxypropyl beta
cyclodextrins for the treatment of Alzheimer’s Disease.
• Orphan Drug Designation for NPC allows market exclusivity for 7 and 12 years in the US and EU,
respectively.
16

17. Management Team &
Board of Directors
17
N. Scott Fine Chairman & CEO
Sharon H. Hrynkow, PhD Chief Scientific Officer
Jeffrey L. Tate, PhD COO, CQO, Director
Michael Lisjak
Global Head of
Regulatory Affairs
Joshua M. Fine Chief Financial Officer
C.E. “Rick” Strattan Director & Founder
Markus Sieger Lead Director
William S. Shanahan Director
F. Patrick Ostronic Director
Randall Toig, MD Director

18. 18
CTD Appoints Global Head of Regulatory
Affairs

19. Mr. Fine has been involved in Investment Banking for over 35 years working on a multitude of debt and equity financings, buy and sell side
M & A, strategic advisory work and corporate restructurings. Much of his time has been focused on transactions in the healthcare and
consumer products area. Mr. Fine has led global transactions in Healthcare to include Medical Devices, Generic Pharmaceuticals, and
Genetics. He also worked with The Tempo Group of Jakarta, Indonesia when Mr. Fine and his family resided in Jakarta.
Mr. Fine was the lead investment banker on the Initial Public Offering of Keurig Green Mountain Coffee Roasters and Central European
Distribution Corporation, a multi-billion-dollar alcohol company. He was also involved in an Equity Strategic Alliance between Research
Medical and the Tempo Group.
Mr. Fine continued his involvement with CEDC serving as a director from 1996 until 2014, during which time he led the CEDC Board's
successful efforts in 2013 to restructure the company through a pre-packaged Chapter 11 process whereby CEDC was acquired by the
Russian Standard alcohol group.
Recently, Mr. Fine served as Vice Chairman and Chairman of the Restructuring Committee of Pacific drilling from 2017 to 2018 where he
successfully led the Independent Directors to a successful reorganization. He also served as Sole Director of Better Place Inc. from 2013
until 2015. In his role, there Mr. Fine successfully managed the global wind down of the Company in a timely and efficient manner which
was approved by both the Delaware and Israeli Courts.
Mr. Fine is currently a Board member of Kenon Holdings Ltd. (NYSE: KEN)
Mr. Fine devotes time to several non-profit organizations, including through his service on the Board of Trustees for the IWM American Air
Museum in Britain. He and his wife, Cathy are also the Executive Producers of “The Concert for Newtown” with Peter Yarrow of Peter,
Paul, and Mary.
Mr. Fine has been a guest lecturer at Ohio State University’s Moritz School of Law.
19
Bio – N. Scott Fine; Chairman & CEO

20. Dr. Sharon Hrynkow is a global health expert whose career has spanned public and private sector leadership roles for over 20 years.
Prior to joining CTD, Dr. Hrynkow served for 3 years as the inaugural President of the Global Virus Network (GVN), a non-profit
organization founded by Dr. Robert Gallo. GVN is a coalition of the world’s top medical virology institutions all working together to prevent
viral pandemics. Before taking the helm of GVN, Dr. Hrynkow spent over 20 years at the National Institutes of Health (NIH) and the U.S.
Department of State, leading major programs and policy efforts to address HIV/AIDS, emerging infectious disease, the health impacts of
climate change, the growing burden of mental health disorders, and training of future clinical researchers. She served as Deputy Director,
then Acting Director, of the Fogarty International Center of the NIH, leading a staff of 70 and with a direct annual Congressional
appropriation of $60 million; and Associate Director of the National Institute of Environmental Health Sciences, whose annual budget
exceeds $1B. At Fogarty, she worked with more than 100 countries to strengthen biomedical research collaboration and launched new
partnerships for NIH, including with Russia, India and China. With her team, she designed and launched programs with US and foreign
universities to train future clinical researchers and leaders in infectious diseases, brain disorders, and cancer, among other priorities. At
the Department of State, Dr. Hrynkow wrote the first U. S. International Strategy for HIV/AIDS published in 1995, and later served as both
Senior Advisor to the Assistant Secretary of State for Oceans, Environment and Science (2011), and Senior Scientist in the Science
Advisor to the Secretary of State’s office (2012). As an advocate for career enhancement for women and girls in science, Dr. Hrynkow
was privileged to build the US delegation for Secretary Clinton for the 55th United Nations Commission on the Status of Women’s session,
and to serve on the delegation.
A neuroscientist trained at the University of Connecticut, she conducted post-doctoral studies in early brain development at the University
of Oslo. She received her B.A. from Rhode Island College.
Dr. Hrynkow has advised numerous bodies on global health and science matters, including as Chair of the American Association for the
Advancement of Science Committee on Science, Engineering and Public Policy; Member of the Institute of Medicine Roundtable on
Environmental Health Sciences, Research and Medicine; and Advisory Board Member for the Canadian Institute on Gender and Health.
She is an elected member of the Council on Foreign Relations and Fellow of the American Association for the Advancement of Science
(AAAS). In January 2019, she was appointed to the Advisory Committee of Division of Earth and Life Studies of the National Academies of
Sciences, Engineering and Medicine. Her awards include the President of the United States Rank Award for Meritorious Senior Executive,
the King of Norway’s Order of Merit, and the Association of Women in Science/Bethesda Chapter’s award for Excellence in Mentoring. In
2013 she was named one of forty extraordinary AAAS Fellows out of 2800 Fellows in recognition of her work in advancing science in
service of society.
20
Bio – Sharon Hrynkow PhD – CSO

21. Board of Directors
21
N. Scott Fine See bio above
C.E. “Rick” Strattan Company Founder
Jeffrey L. Tate, PhD
Chief Operating Officer – Formerly Associate Director,
Biotechnology Institute, University of Minnesota
Markus Sieger
CEO Polpharma Group; Executive Board Member Medicines for
Europe
William S. Shanahan
Former President of Colgate-Palmolive; Currently serving as a
Director of Visa U.S.A Inc and Duracell International
F. Patrick Ostronic
Currently CFO and Director of U.S. Pharmacia; Director Novit
L.P
Randall Toig, MD
President Gold Coast Gynecology – Board Certified gynecologist
and gynecologist surgeon.

22. Scientific Advisory Board
22
Rita Colwell, PhD Co-Chair
Distinguished Professor, U. of Maryland, former
Director National Science Foundation
Sharon Hrynkow, PhD Co-Chair CTD, bio above
M. Flint Beal, MD
Professor of Neurology and Neuroscience, Weill
Cornell Medical College
Caroline Hastings, MD
Fellowship Director, Pediatric
Hematologist/Oncologist, UCSF Benioff Children’s
Hospital Oakland
Benny Liu, MD
Gastroenterologist, Alameda Health System and
UCSF Benioff Children’s Hospital Oakland

23. • Phase II in Europe/Israel and Phase I in U.S. - recruiting, dosing in Niemann
Pick Disease Type C (NPC)
• NPC and AD, Compassionate Use Program ongoing in multiple countries
• Granted Orphan Drug Designation (ODD) by the U.S. Food and Drug
Administration and European Medicines Agency; Rare Pediatric Disease
Designation (U.S.) and Fast Track designation (U.S.)
• Alzheimer's Disease moving towards Phase I
• NPC represents significant $500mm+ annual addressable market
• Alzheimer’s Disease $1 Billion+ Opportunity
Approximately $10 million invested by insiders
• Recently closed $7.4M institutional equity financing.
• Cyclodextrins are modifiable for multiple therapeutic areas
• Company is leader in Intravenous use of cyclodextrins
• ODD gives market exclusivity for 7- 12 years
• The company holds trademark, copyright and trade secret intellectual
property around the Trappsol® Cyclo™ product.
Investment Highlights
Trappsol®
Cyclo™
Active clinical programs in
Niemann Pick Disease and
Alzheimer's Disease
Large Market
Opportunity
Strong Management
Team & Board
Robust
Cyclodextrin
Portfolio & IP
23
Strong Balance
Sheet

24. Thank You!
24

25. IT adds no additional benefit to IV: compassionate data
25
In a set of patients for which CTD has years of data, IV Trappsol® Cyclo™ either stabilizes NPC disease
(lowermost line and upper right lines) or is associated with clinical improvements, as exhibited by lowering of
NPC Severity Scores following IV Trappsol® Cyclo™ administration over time. Note: all patients added
intrathecal administration to IV within 1 year to 2 years, with limited additional benefit observed.
0
5
10
15
20
25
30
35
40
45
50
-12 -10 -8 -6 -4 -2 0 2 4 6 8 10
NPCClinicalSeverityScoreScale
Years pre/post initiation of IV Cyclodextrin
NPC Severity Scores: Pre- and Post-treatment
001
002
003
004
005
006
007

26. Global Investigators
26
Caroline Hastings, MD
• Pediatric hematologist/oncologist, Co-
PI, UCSF Benioff Children’s Hospital
Oakland
Benny Liu, MD
• Gastroenterologist, Alamada Health
System and UCSF Benioff Children’s
Hospital Oakland, Co-PI
Darius Adams, MD
• Clinical geneticist and pediatric
metabolic disease expert, PI,
Morristown, NJ
Robin Lachmann, MD
• Metabolic disease expert and PI,
University College London
Reena Sharma, MD
• Metabolic disease expert, and
coordinating lead for Phase I/II trial, PI
for Salford Royal Trust site, UK
Ronen Spiegel, MD
• Clinical geneticist and Chair of
Pediatrics, PI, Emek Medical Center,
Israel
Orna Staretz, MD
• Neonatologist, PI, Soroka Medical
Center, Israel
Martin Paucar Arce, MD, PhD
• Neurologist, PI, Karolinska Institute,
Sweden
Julian Raiman, MD
• Pediatric metabolic disease expert, PI,
Birmingham Childrens, UK
Maurizio Scarpa, MD
• Metabolic disease expert and
Coordinator, European Reference
Network for Hereditary Metabolic
Diseases, PI for site at Udine University
Hospital, Italy

27. Alan Boyd, MD
• Leading pharmaceutical physician and
CTD regulatory advisor
Frances Platt, PhD • World leader in biochemistry of lipids
Arndt Rolfs, MD • CEO at Centogene
David Begley, PhD • Professor at Kings College, London
World-Class Medical and Scientific
Advisors
27

28. Adverse Event (AE) Toxicity Grading (CTCAE)
Grade 1 (Mild) Grade 2 (Moderate) Grade 3 (Severe)
No. of Events 5 6 3
Related AE’s nil Infusion reaction*, Hypoxia*,
Fever*
Hypersensitivity Pneumonitis*,
Hearing loss*
Not Related
AE’s
Hematuria,
Hearing loss x
3, IV Infiltrated
Headache, Nausea, Vomiting Hearing Loss
First 4 Subjects – US trial
 Adverse Event Profile shown below
Overall, a positive safety profile to date
Safety Profile
United
States

29. Patient:
Clinically perceptible reduced hearing of 1 month duration
Took a flight with a concurrent URI – conductive hearing loss likely. Fully resolved.
Patient:
Subject experienced an SAE of hypersensitivity pneumonitis resulting in their withdrawal from the study after the
first infusion. The subject and family noted a hearing loss and so audiology was performed after their withdrawal.
A sensorineural loss was diagnosed and was likely related to an immune-mediated global inflammatory process.
Of note also was a complex medical and concomitant medication history making causality association difficult.
The reduction in hearing resolved concurrently with an improvement in the hypersensitivity associated interstitial
lung disease findings.
Patient:
Variable hearing loss from a Grade 1 to Grade 3 severity over the course 3 months. Not perceived by the
subject and is fully resolved.
X = 3 reported AEs related to a
reduction in hearing
Safety Profile - Hearing
United
States

30. Adverse Event (AE) Toxicity Grading (CTCAE) - N = 64 AEs
Grade 1 (Mild) Grade 2 (Moderate) Grade 3 (Severe) Grade 4 (Life-
Threatening)
No. of Events 42 12 8 2
* Related AE’s 15 - ↑bowel movement, fever,
↑ALT, ↑AST, tinnitus, worsened
hearing at higher frequencies
1 - ↑bowel movement 0 0
^Not Related
AE’s
27 - including, ↓platelets, raised
CRP, coughing, vomiting,
weight loss, nausea, fall,
intermittent absence seizures
11, including, rash,
seizure, cough, vomiting,
headache, anaemia
X 1 anaemia
X 7 in the same
subject for intermittent
seizures / hospitalized1
Aspiration
pneumonia,
declining health /
unconscious1
First 4 Subjects EU/Israel trial: Adverse Event (AE) profile shown below
 AE’s Largely of a Grade 1-2 (mild to moderate) severity
 9 Laboratory AE’s
 2 hearing related AE’s, both mild
• Related incorporates events at least Possibly or Probably related ^ Not Related incorporates events considered Unlikely and Not Related
• ALT (ALAT) = Alanine transferase, AST (SGOT)= Aspartate Transaminase
• 1 reported as Serious Adverse Events (SAE’s) – discussed on next slide
Safety Profile Europe

31. Serious Adverse Events (SAE’s) -- 9 events reported in 2 subjects
SAE: Intermittent seizures requiring hospitalisation. This was discussed and considered as not related to study
treatment but down to non-compliance with their normal anti-epileptic medication. The subject was withdrawn
from the study by family despite positive improvements in their disease
SAE: Hospitalised intermittently for general healthy deterioration, aspiration pneumonia and non-study medication
overdose. This subject was also withdrawn, by the physician, due to missed dosing and the deterioration in their
general condition.
Hearing Related Adverse Events
2 events reported in 1 subject
An initial tinnitus was reported and documented at the patients Week 2 Study Visit. The event was self-limiting,
lasting only48 hours and resolved. At the Week 24 Study Visit, routine audiometry was performed and a reduction
of hearing at higher frequencies was noted. However, with no natural history data in this patient population with
regards to hearing, and the examination being performed at frequencies outside of the protocol defined range,
interpreting this was difficult and continues to be monitored.
EuropeSafety Profile

32. Cholesterol Precursors
32
Individual Serum levels of Lathosterol at each visit
from 4 subjects in the 101 study and 4 subjects in 201 study
Mean Serum levels of Lathosterol
Individual Serum Levels of Desmosterol at each visit
from 4 patients in the 101 study and 4 subjects in 201 study
Mean Serum Levels of Desmosterol
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
Screen 1 Screen 2 Pre
infusion
D2 Post D3 D4 D5 D8 D15
ug/ml
0
0.5
1
1.5
2
2.5
Screen 1 Screen 2 Pre infusion D2 Post D3 D4 D5 D8 D15
Time
Mean ug/ml
0.000
0.200
0.400
0.600
0.800
1.000
1.200
1.400
1.600
Screen 1 Screen 2 Pre infusion D2 Post D3 D4 D5 D8 D15
Time
ug/ml
0.540
0.560
0.580
0.600
0.620
0.640
0.660
0.680
0.700
0.720
0.740
Screen 1 Screen 2 Pre
infusion
D2 Post D3 D4 D5 D8 D15
ug/ml
Each colored line represents a unique patient.

33. Cholesterol Metabolites
33
Individual Patient Values for Serum 4B-hydroxy cholesterol Mean values for Serum 4B-hydroxy cholesterol
Individual Patient Values for Serum 27-hydroxycholesterol Mean values for serum 27-hydroxy cholesterol
Each colored line represents a unique patient.

34. 34
ng/ml
Units
Weeks
Plasma Levels of Lyso – 509
US Study
United
States
Each colored line represents a unique patient.

35. 35
0
2
4
6
8
10
12
14
16
1 2 8 10 12 14 18 20 22 24 26 28
Weeks
Plasma Levels of Lyso – 509
Europe/Israel Study
Europe
ng/mlng/ml
Units
Each colored line represents a unique patient.

36. 36
0
5
10
15
20
25
30
35
40
45
50
0h 4h 8h 12h
HPBCDug/ml
H after start of infusion
Trappsol® Cyclo™ in CSF – US Study
United
States
Each colored line represents a unique patient.

37. 37
Combined Data US trial and EU/Israel trial
Trappsol® Cyclo™ in CSF
ug/ml
Units
H after start of infusion
Each colored line represents a unique patient.

38. pg/ml
Baseline End of Infusion Dose 1 End of Infusion Dose 7
Levels of Tau in CSF
United
States
ng/ml
Units

39. 39
Visit 2/baseline Visit 2/baselineVisit 2/baselineVisit 18/Week 24 Visit 18/Week 24 Visit 18/Week 24 Visit 30/Week 48
Levels of Tau in CSFpg/ml Europe
ng/ml
Units

40. NPC Clinical Severity Score
• Widely used tool in clinical research community starting in 2010
• Based on 9 major domains, or features of NPC disease: eye movement,
ambulation, speech, swallow, fine motor skills, cognition, hearing, memory, and
seizures.
• And 8 modifying domains: Gelastic cataplexy, narcolepsy, behavior, psychiatric,
hyperreflexia, incontinence, auditory brainstem response, and respiratory.
• Each major domain is scored 0 – 5, modifying domains 0 – 2 with 0 being normal
or no history of the disease manifestation. Most severe patients are scored 61 with
this tool.
40

41. • For patient 1 (yellow): The improvement in total score of 3 points (compared with baseline ) is due to
reductions in severity in the eye movement (1 to 0), fine motor skills (2 to 1) and psychiatric modifier (1
to 0). For patient 2 (green): The improvement in total score (compared with baseline) is due to
reductions in severity in eye movement (1 to 0), cognition (5 to 3), gelastic cataplexy (2 to 1) and
incontinence (1 to 0). However, ambulation worsened (1 to 2) as did speech (3 to 4). Total score
change reflects an improvement of 3 points. N=2
41
NPC Clinical Severity Scores Europe

42. Physician Overview – US Study
Following completion of the 14 week/7 dose treatment protocol:
4 of 6 patients report increased alertness, focus, enhanced communication and
speech fluency.
3 of 6 patients note increased strength and motivation leading to increase in
movement or ambulation.
2 patients remain clinically stable.
1 patient was withdrawn from the trial due to hypersensitivity.
Global Impression of Disease scores, standardized tool, to be analyzed.
42
United
States

43. Clinical Efficacy Summary
Europe/Israel and US
• Initial clinical efficacy findings are encouraging.
• From the EU/Israel trial, both patients out of the initial four who completed the 48
week trial improved overall NPC Clinical Severity Score by 3 points, each in
different ways. Disease specific features, including fine motor, cognition,
incontinence and eye movements, improved.
• From the US trial, most patients who have completed the trial so far have
remained stable or improved in specific features of the disease.
43