CONFIDENTIAL

February 17, 2015

Theralase Technologies Inc.

Roger Dumoulin-White
President,
Chief Executive
Theralase
Technologies
Inc.Officer
AGM Corporate
Presentation
Corporate
Presentation
December 2016 Chapter Title Section

Forward Looking Statements

Certain statements contained or incorporated in this presentation, which deal with the financial condition and operating results of Theralase
Technologies Inc. (Theralase or the Company), include information, analyses and projections as to future corporate developments
which are currently in the planning stage, and on the projected operating financial performance of the Company, which constitute forwardlooking statements. Such forward-looking statements, made with special reference to the Companys ongoing technologically complex
healthcare and medical device research and development efforts, which may include in-house and independent clinical trials, testing new
medical technologies and their applications, involve known and unknown risks and uncertainties that could cause actual events and results
to differ materially from those estimated or anticipated and which may have been implied or expressed in such forward-looking statements.
No conclusions as to the successful outcome of the ongoing and planned research and development projects in which the Company is
involved are intended or implied nor can they be foreseen or predicted prior to definitive corporate announcements as to their outcome.
Certain forward looking statements are identified by words such as believe, anticipate, should, could, would, estimate,
expect, intend, plan, expect, project, may, and will and the negative of such expressions, although not all forward looking
statements contain these identifying words, any statements that refer to expectations, projections or other characterizations of future events
or circumstances are forward looking statements. Although Theralase believes that the expectations reflected in any forward looking
statements made in this presentation are reasonable, such statements are based on a number of assumptions which may prove to be
incorrect; including, but not limited to assumptions related to the risks and factors set out in the Companys final base shelf prospectus and
prospectus supplement (collectively, the Prospectus).
Accordingly, no assurances can be given that any of the events or circumstances contemplated by any such forward looking statements will
transpire or occur or, if any of them transpire or occur what impact they will have on Theralases results of operations or financial condition.
A more complete list of risks and uncertainties inherent to the Companys industry can be found in the Prospectus.

Furthermore, the forward-looking statements contained in this presentation are made as of the date hereof. The Company does not
undertake any obligation to update publicly or to revise any of the included forward-looking statements, whether as a result of new
information, future events, or otherwise, unless required by applicable laws. The forward-looking statements contained in this presentation
are expressly qualified by this cautionary statement and the cautionary statement under the heading Forward Looking Statements in the
Prospectus.
All references to dollars herein are to Canadian dollars except as otherwise indicated.

Corporate Overview
Theralase is a medical device and drug development company that
utilizes proprietary laser technologies across two operating
divisions.
Therapeutic Laser Technology (TLT) Division:
Manufacture and sell a clinically proven and highly
effective, patented, FDA cleared commercial cold
laser technology
Used by doctors and other healthcare professionals
to treat various nerve, muscle and joint conditions to
help patients eliminate pain, reduce inflammation
and accelerate tissue healing
Shown to heal patients more safely, faster and more
effectively than other competitive products on the
market

Corporate Overview
Photo Dynamic Therapy (PDT) Division:
Developing laser activated, light-sensitive
compounds called Photo Dynamic Compounds
(PDCs) that are nontoxic to healthy tissue and able
to localize to cancer cells and destroy them when
exposed to laser light
In-vitro and in-vivo pre-clinical studies show high
efficacy in the destruction of various cancers

Phase 1b study expected to begin in 4Q2016 for

clinical evaluation in patients who have Non Muscle
Invasive Bladder Cancer (NMIBC) and are
refractory to standard of care at Princess Margaret
Cancer Center, University Health Network, one of
the top cancer research centers in the world
Patent pending laser to activate PDCs is proprietary
to Theralase PDCs and able to activate them at
various tissue depths for patient-specific
treatments
4

Key Theralase Facts

More than $25M invested to date in both divisions to develop and commercialize
advanced medical laser technologies used to eliminate pain and destroy cancer
Risk diversification and reward through the combination of a proven commercial laser
therapeutics technology that is now entering a rapid growth period with strong initial
evidence for a future breakthrough oncology program

13 issued patents, 17 patents pending at the national phase and 3 pending at the
international PCT phase
Next generation therapeutic laser dramatically increases efficacy over existing
technologies for a pain management market that exceeds $100B in the US alone

Therapeutics division has a high margin, highly scalable, recurring revenue model
Oncology PDT Division has shown to be more than 99% effective in killing cancer when
light activated with 0% toxicity to healthy tissue during in-vitro and in-vivo testing
Company expects to commence a Phase 1b Clinical Study for Non-Muscle Invasive
Bladder Cancer (NMIBC) in 4Q2016
Company led by a proven and experienced management team that has partnered with
world renowned doctors at leading medical centers
5

Key Customers
Business relationships with world-class research institutions and
professional sports teams:
Research Institutions

Sports Teams and Organizations

Therapeutic Laser Division

Second generation technology (TLC-1000)
currently installed at approximately 600 locations in
Canada and 400 locations in the US and
internationally

Clinically proven via a FDA cleared, double blind,

randomized controlled clinical study to eliminate
pain 1
Up to approximately 65% gross margin (35%
COGS) as of September 30, 2016
Generates approximately $2 M annually as of
December 31, 2015
Used by numerous professional athletes to return
to competition faster and stronger

Marquina, Nelson, Dumoulin-White, Roger, Mandel, Arkady*, Lilge, Lothar, Laser therapy applications for osteoarthritis and chronic joint pain A randomized
placebo-controlled clinical trial, Photon Lasers Med 2012; 1(4): 299307

TLC-2000
Cell Sensing technology uses patented algorithms to
determine the depth of a condition and the amount of laser
light required to optimally treat it, then delivers this laser light
automatically (Uses set powers and time for chronic knee
pain)
Dramatically increases efficacy over existing technologies by
precisely targeting injured tissue

8 issued international patents

FDA cleared /Health Canada approved in December 2015
Patients report 90% efficacy rate in healing nerve, muscle and
joint conditions
Rotator cuff clinical study to be commenced with Dr. James
Andrews in 1Q2017

Up to 65% gross margin business (35% COGS) as of

September 30, 2016

Pain Market
US pain market exceeds $100B annually and
growing rapidly2
45% of this population remain in significant pain post
surgery or prescribed pain medicine3 Patients are
seeking alternative treatment methods as their pain
is still present. Doctors are not prescribing pain
medication due to high addiction rates and
government restrictions
TLC-2000 expected to be eligible for a unique
reimbursable Current Procedural Terminology
(CPT) code in the U.S. for national insurance
reimbursement due to Cell Sensing technology.
This allows easier sale of the TLC-2000 to doctors
and physical therapists that rely on CPT codes to
bill, as well as allows access to Medicare and
Medicaid

2. Institute of Medicine of the National Academies Report. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research, 2011. The
National Academies Press, Washington DC.
3. Peter D. Hart Research Associates. Page 3. KEY FINDINGS. Americans in Pain.

Practitioner Business Model

Approximately 600 TLC-1000 systems installed in Canada and 400 TLC-1000 systems
installed in the United States and internationally
Of the 1,000 locations, healthcare practitioners charge between $20 to $150 per 10 to
15 minute treatment
On average, they charge $50 per treatment per treatment session
These healthcare practitioners perform between 100 and 500 treatment sessions per
month, with an average of 200 treatment sessions per month
Healthcare practitioner generates on average $50 x 200 treatment sessions or $10,000
per month
Theralase TLC-2000 retails for between $20,000 (1 probe) to $40,000 (4 probe) or $400
to $800 per month on a 5 year lease* (average $500 per month for 2 probe laser system)

Up to 2000% Monthly Return on Investment ($10,000 / $500 = 20 x or 2000%)

*Lease price includes: TLC-2000 product, in-person and video training, 5 year warranty,
5 year marketing support, direct patient referrals and 5 year software updates
10

Theralase Business Model

Moving away from a capital equipment model to a recurring
revenue model
Theralase plans to generate recurring fees of on average $500 per month per unit
Direct sales force of 5 Territory Sales Managers in Canada and 5 (3 currently) in United
States (expected to be increased to 13 in US in 2017), currently selling the TLC-2000

Theralase has partnered with the largest medical leasing companies (National Leasing in
Canada and Partners Capital Group in the United States) to provide 5 year financing to
healthcare practitioners allowing Theralase to be paid in full immediately upon delivery
and installation of product
Theralase repurchases the asset from the lease company at the end of the 5 year term
for 2% of value ($25,000 product purchased for $500)
At end of lease, practitioner has the following options:
Return equipment to Theralase and discontinue use
Pay 10% residual to Theralase, keep technology and discontinue support
Pay $200 to $400 per month (average $250 per month) indefinitely to maintain warranty and
marketing support
Purchase latest Theralase technology and recommence lease process
11

Photo Dynamic Therapy Division

Effective:

Patented anti-cancer drugs able to destroy cancer cells > 99% when
light activated (Lead drug is TLD-1433, a Ruthenium based PS) based
on pre-clinical studies

Safe:

Virtually 0% toxicity to healthy tissue

Targeted:

Targets only cancer cells

Immune Response: Proven ability to prevent recurrence of cancer even after repeated
exposures

Diagnostic:

Proven ability to detect cancer cells

Versatile

Able to be activated at a various tissue depths

Issued U.S. Patents Licensed to Theralase: 6,962,910, 7,612,057, 8,148,360, 8,445,475

Pending U.S. Patent Applications Licensed to Theralase: PCT/US14/30194, 13/863,089,
PCT/US13/36595
Highly Accredited: Preclinical research performed at the one of the top 3 cancer research
institutes in the world, Princess Margaret Cancer Centre, University
Health Network (UHN) has substantiated these results and the data has
been peer-reviewed and published
Clinical Studies:

Phase Ib clinical study for bladder cancer expected to commence in

4Q2016. Theralase expects to submit to FDA an Investigational New Drug
(IND) application for the Phase II clinical study in 1Q2017
12

Anti Cancer Technology

Efficacy

Safety
120

45 J cm-2 120
90 J cm-2
100

100

80

Cell Kill (%)

Cell Kill (%)

80

45 J cm-2
90 J cm-2

60
40

60
40

20

20

0
0.00125 0.0025

0.005

0.01

0.02

Concentration (mM)

0.04

0
0.00125 0.0025

0.005

0.01

0.02

0.04

Concentration (mM)

In-vitro study completed at PMCC with HT-1376 (human bladder cancer cell line) with TLD-1433 (Theralases lead
PDC) comparing cell kill (y axis) versus TLD-1433 concentration (x axis)

The left hand graph shows HT1376 cancer cells mixed with various concentrations of TLD-1433, but not light activated,
demonstrating a high safety and tolerability, as there is virtually no cell kill
The right hand graph shows HT1376 cancer cells mixed with various concentrations of TLD-1433 and light activated at
two different levels of light (45 J/cm2 and 90 J/cm2) demonstrating up to 100% efficacy at various concentrations of
TLD-1433

13

TLD-1433 Effectiveness
Safety

Mouse colon cancer

(carcinoma)

80

80

Cell Kill (%)

100

Cell Kill (%)

100

60
40
20
0

Efficacy

ALA
TPDC

60
40
20
0

0.00016 0.0003 0.0008 0.025

Concentration (mM)

0.00016

0.0003 0.0008
0.025
Concentration (mM)

In-vitro study completed at PMCC with CT26.WT (mouse colon carcinoma cancer cell line) with TLD-1433 (Theralases
lead PDC) comparing cell kill (y axis) versus TLD-1433 concentration (x axis)
The left hand graph shows CT26.WT cancer cells mixed with various concentrations of TLD-1433, but not light
activated, demonstrating a high safety and tolerability, as there is virtually no cell kill
The right hand graph shows CT26.WT cancer cells mixed with various concentrations of TLD-1433 and light activated
at 90 J/cm2 demonstrating up to 100% efficacy at various concentrations of TLD-1433
Amino Levulinic Acid (ALA) has virtually no impact on CT26.WT cancer cells at these concentrations
Up to 100% cell kill is achieved at concentrations as low as 0.00016 mM or 0.16 nM (micrograms of TLD-1433)

14

TLD-1433 Effectiveness (Continued)

100
80
60
40
20
0

Cell Kill (%)

Rat brain cancer

(glioma)

0.0001 0.0002 0.0005 0.017

Concentration (mM)

Efficacy

Human brain cancer

(glioblastoma)

100
80
60
40
20
0

ALA

Cell Kill (%)

Safety

TPDC

0.0001 0.0002 0.0005 0.017

Concentration (mM)

In-vitro study completed at PMCC with U87 (human glioblastoma brain cancer cell line) and F98 (rat brain glioma
cancer cell line) with TLD-1433 (Theralases lead PDC) comparing cell kill (y axis) versus TLD-1433 concentration (x
axis)
The left hand graph shows U87 and F98 cancer cells mixed with various concentrations of TLD-1433, but not light
activated, demonstrating a high safety and tolerability, as there is virtually no cell kill. The right hand graph shows U87
and F98 cancer cells mixed with various concentrations of TLD-1433 and light activated at 90 J/cm2 demonstrating up
to 100% efficacy at various concentrations of TLD-1433
ALA has virtually no impact on U87 and F98 cancer cells at these concentrations. The current limitation of ALA and
Photofrin is that they are porphyrin based PSs that are predominantly systemically injected and activated by red laser
light, limiting their use to various cancers. Photofrin was approved for bladder cancer in 1993, but has never been used
clinically due to the toxicity and morbidity exhibited to the bladder structure. They also may render the patient
extremely light sensitive for 30 to 90 days post treatment

15

First Clinical Bladder Cancer

Bladder Cancer by the Numbers:4,6
$3.9 Billion (2016), 76,960 new cases, 16,390 deaths in the US each
year
Bladder cancer starts from the inside of the organ and grows into the
organ, making it a prime target for intravesical PDT
5th most common cancer, 4th in men, 8th in women
70% of new bladder cancer cases are early stage disease and 90%
of bladder cancers are Transitional Cell Carcinoma (TCC)
Current Standard of Care:5
Early stage disease (Carcinoma In-Situ (CIS), Ta, T1): Trans Urethral Resection of
the Bladder Tumour (TURBT) followed by treatment with bacillus Calmette-Gurin
(BCG) 5 year survival rate of 96%
Mid Stage disease (T2, T3a/b): Entire bladder removed along with nearby reproductive
organs and lymph nodes in a procedure called a radical cystectomy - 5 year survival rate
of 34 to 70% depending on progression of disease
Late stage disease (T4): Disease has spread to distant sites, such as the bones, liver and
lungs and is generally regarded as incurable - 5 year survival rate of 5%
4. American Cancer Society
5. http://www.cancer.net/cancer-types/bladder-cancer/statistics
6. National Cancer Institute

16

In-Vivo Targeted Therapy

(>>99% destruction of bladder cancer tumours)

Left Image indicates elongated bladder removed from orthotopic rat model (in-situ AY-27 rat bladder cancer cells) after
intravesical instillation of TLD-1433 PDC demonstrating that TLD-1433 (yellow compound) localizes preferentially to
bladder cancer tumours at a rate 180 times greater than that of healthy urothelium. (Arrows indicate localization of
TLD-1433 in main bladder cancer tumours and in microscopic tumours (may indicate why TURBT / BCG procedure
has 80% recurrence issue
Center Image indicates biopsy of bladder cancer prior to PDT treatment demonstrating 100% viable bladder cancer
cells
Right Image indicates biopsy of bladder cancer after PDT treatment demonstrating virtually 0% viable bladder cancer
cells as verified by histopathology (>>99% destruction of bladder cancer tumours)

17

Immune Response
First slide 350,000 colon cancer cells injected into
mouse subcutaneously (below skin surface). Tumor
allowed to grow to approximately 5 mm in diameter
and then 53 mg/kg of TLD-1433 injected intra-tumorly
Second slide TLD-1433 allowed to absorb into
colon cancer cells for 4 hours. (pre-light activation)
Third slide 24 hours after light activation, colon
cancer cells demonstrating clear necrosis (cell death)
Fourth slide same mouse 20 months later (mice
only live 18 to 20 months) demonstrating no cancer
cells (no recurrence) and no scarring (no destruction
of healthy cells). Same mouse cohort injected up to
three times with 350,000 colon cancer cells, with no
further intervention. Cancer is unable to grow
suggesting that the immune system (Killer T cells)
have memorized the signature of the colon cancer
cells and have provided an immune-mediated
response preventing recurrence

Cancer necrosis
(cell death)

18

Mechanisms of Action
Transferrin combines with PDC to target cancer cells and destroy
them

Transferrin is an endogenous (naturally occurring) glyco-protein that transports iron (Fe) to every cell in our body. Iron is
a transitional VIII metal, as is Ruthenium (Ru) and Osmium (Os) (main centers of Theralase PDCs); therefore, TLD1433 (Ru centered PDC) is able to combine with transferrin to be transported through the blood stream to every cell with
a Transferrin Receptor Site (TfR). It is well documented that cancer cells have a larger number of transferrin receptors
versus healthy cells.7,8 Thus, the combination of TLD-1433 with endogenous transferrin provides a selectivity and
specificity of TLD-1433 to a wide variety of cancer cells, allowing TLD-1433 to cross the cancer cell cellular membrane
into the interior of the cell; whereby, when it is light activated it produces a powerful cytotoxic (cell killing) singlet oxygen
known as Reactive Oxygen Species (ROS) making it a very potent cancer destruction agent to a wide range of cancer
cells. (i.e.: bladder, lung, brain and melanoma to name a few). The colored slide indicates DAPI staining, where the
nucleus of the cancer cell stains blue and TLD-1433 stains red, suggesting that TLD-1433 localizes to the cytoplasm of
the cell and not the nucleus.
7. Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation. Jeong SM, Hwang S, Seong RH
8. A novel transferrin receptor-targeted hybrid peptide disintegrates cancer cell membrane to induce rapid killing of cancer cells. Megumi Kawamoto, Tomohisa Horibe,
Masayuki Kohno, Koji Kawakami

19

Next Steps
Therapeutic Laser Technology (TLT) Division
Complete:
4Q2015 - Health Canada Approval and FDA Clearance of Theralase TLC-2000 Therapeutic Laser
2Q2016 - Hiring of 2 Canadian Territory Sales Managers (TSMs) for a total of 5, including the
National Sales Manager (NSM)

3Q2016 - Hiring of 2 United States TSMs

Pending (Approximate Anticipated Timing):
2Q2017 - Hiring additional United States TSMs

20

Next Steps
Photo Dynamic Therapy (PDT) Division
Complete:
4Q2015 - Health Canada Clinical Trial Application (CTA) approval and University Health Network
Research Ethics Board (UHN REB) Approval
4Q2016 - Health Canada Investigational Testing Authorization (ITA) approval and commence Phase
Ib clinical study for NMIBC
Pending (Approximate Anticipated Timing):
1Q2017 - FDA pre-Investigational New Drug Application (IND) approval for NMIBC
3Q2017 - FDA pre-Investigational New Drug Application (IND) approval for brain cancer.
Commence enrolling patients into Health Canada and FDA Phase Ib clinical study for brain
cancer
4Q2017 - Complete Health Canada Phase Ib clinical study for NMIBC
1Q2018 - Commence enrolling subjects into Health Canada / FDA / CE Phase II clinical study for
NMIBC

3Q2018 - Complete Health Canada and FDA Phase Ib clinical study for brain cancer
4Q2018 - Commence enrolling patients into Health Canada / FDA / CE Phase II clinical study for
brain cancer
4Q2019 - Complete Health Canada / FDA / CE Phase II clinical study for NMIBC

4Q2020 - Complete Health Canada / FDA / CE Phase II clinical study for brain cancer
21

Management Team
Roger Dumoulin-White President & Chief Executive Officer

President and CEO of Theralase Technologies Inc. since 2004 (Theralase Inc. since 1994)
Before founding Theralase Inc., served as a Product Team Manager with Ford Electronics
Manufacturing Corporation, a division of Ford Motor Corporation (NYSE:F), where he
managed a $40 million a year business (subset of $400 million annual business), with
approximately 400 employees reporting to him (subset of 2,500 total employees)
Graduated from the University of Western (London, Ontario) with a bachelor degree in
Electrical Engineering (B.E.Sc)

Dr. Arkady Mandel Chief Scientific Officer

One of the key founders of the therapeutic use of lasers in dermatology and other areas of
clinical medicine, as well as the originator and developer of phototherapy methods

Over 100 original papers and scientific monographs to his name, combined with over 200
international patents

Dr. Mandel earned his designation as a medical doctor from the Moscow State Medical
University

Doctor of Science accreditation majored in: biochemistry, microbiology, immunology,

biophysics, and photobiology

22

Advisors (TLT Division)

James Andrews, MD:
World renowned orthopaedic sports surgeon. Founder of the American Sports Medicine
Institute (ASMI) President and Chairman of the Andrews Research and Education
Foundation dedicated to prevention, education and research at the Andrews Institute.
Mentored more than 314 orthopaedic/sports medicine Fellows and more than 84 primary
care sports medicine Fellows who have trained under him through the Sports Medicine
Fellowship Program

Jeffrey Dugas, MD:

Orthopaedic sports surgeon. Member of American Academy of Orthopedic Surgeons
(AAOS), ASMI, International Cartilage Repair Society, Treats all types of orthopedic sports
injuries, including injuries of the shoulder, elbow and knee, including total joint replacement
surgery of the shoulder and knee

Lyle Cain, MD:

Orthopaedic sports surgeon. Specializes in arthroscopy and treatment of sports related
injuries, as well as open and arthroscopic treatment of knee, ankle, shoulder and elbow
injuries. Performs surgical joint replacement for arthritis of the knee and shoulder. Certified to
treat cartilage injuries in the knee with articular cartilage implantation and meniscal
transplantation

Kevin Wilk, DPT:

Distinguished career as a clinical physical therapist for the past 29 years and as a leading
authority in rehabilitation of sports injuries and orthopaedic lesions. Provided significant
contributions to laboratory research, bio-mechanical research and clinical outcome studies

23

Advisors (PDT Division)

Michael Jewett, MD: (UHN)
Professor of Surgery (Urology) at the University of Toronto, Surgical Oncology at Princess Margaret Cancer
Centre, University Health Network (UHN). Clinical practice is in urologic oncology with research interests in
testicular cancer and superficial bladder cancer

Lothar Lilge, Ph.D.: (UHN)

Professor in the Department of Medical Biophysics, University of Toronto and Senior Scientist at the Ontario
Cancer Institute, Princess Margaret Cancer Centre, UHN. Research is focused on Photo Dynamic Therapy
(PDT), optical diagnostics, destruction of cancer and bacteria by light activated PDTs and the use of light as a
microscopic tool for biomedical research

Ashish Kamat, MD: (MD Anderson)

Uro-oncologist. Internationally recognized expert in urologic oncology and an authority in the management of
urologic cancers. Expertise in bladder cancer, organ sparing and minimally invasive techniques. Maintains an
active research portfolio with a focus on efforts to develop novel therapies and identifying predictors of response
to therapy (e.g. intravesical immunotherapy), as a first step towards personalized cancer therapeutics. Initiated,
led and been active in several large studies including multinational trials in bladder cancer, with findings
published in high impact journals

Michael ODonnell, MD: (University of Iowa)

Uro-oncologist. Long history of focusing on bladder immunology and bladder cancer immunotherapy,
particularly the anti-cancer mechanisms of bacillus Calmette-Guerin (BCG) and its enhancement with
combination therapies. Recently headed a national trial of bladder cancer treatment utilizing BCG plus interferon
(a natural protein which induces healthy cells to combat disease) comprised of over 1,000 patients and holds
several U.S. patents for his work

Brian Wilson, Ph.D: (UHN)

Senior Scientist and Head of the Applied Biophotonics group at Princess Margaret Cancer Centre, UHN
Professor in the Department of Medical Biophysics at the University of Toronto. Research focus of the Applied
Biophotonics group is the development and application of new therapeutic and diagnostic techniques based on
the use of lasers and other optical technologies

24

Key Metrics
Company Information
In Business Since

1994

Number of Employees

34

Ticker
Corporate and Head Office

TSXV:TLT, OTC:TLTFF
1945 Queen St. East, Toronto, ON,
M4L 1H7, Canada

President and CEO

Roger Dumoulin-White

Work

1-866-THE-LASE (843-5273) x 225

Email

rwhite@theralase.com

Website

www.theralase.com

Market Data (As of December 20, 2016)

Stock Price
52 Week Hi/Lo
Market Capitalization

C$0.28
C$0.455/$0.175
C$34 M

Basic Shares Outstanding

121,284,062

Warrants

35,290,539

Options

8,690,000

Fully Diluted Shares Outstanding

Insider Ownership
Institutional Ownership

165,264,601
6.8% (8.9% fully diluted)
20%

25

Research - TLT Division

1. Action of a Diode Laser in Orthopaedics and Traumatology:
http://theralase.com/wp-content/uploads/2014/09/Action-of-Diode-Laser-in-Orthopaedic-and-Traumatology.pdf
2. A Renaissance in Low-Level Laser Therapy:
http://theralase.com/wp-content/uploads/2014/05/A-Renaissance-in-Low-Level-Laser-light-Therapy.pdf
3. A role of INOS Gene Expression in the Anti-Inflammatory and Tissue Protection Mechanisms of 905 nm Pulse:
http://theralase.com/wp-content/uploads/2014/05/A-Role-of-iNOS-Gene-Expression-in-the-Anti-inflammatory-and-Tissue-ProtectiveMechanisms-of-905-nm-Pulse.pdf
4. In-Vivo Effects of Low Level Laser Therapy on Inducible Nitric Oxide Synthase:
http://theralase.com/wp-content/uploads/2014/05/In-Vivo-Effects-of-Low-Level-Laser-Therapy-on-Inducible-Nitric-Oxide-Synthase.pdf
5. Laser Therapy Applications for Osteoarthritis and Chronic Joint Pain A Randomized Placebo Controlled Clinical Trial:
http://theralase.com/wp-content/uploads/2014/05/Laser-Therapy-Applications-for-Osteoarthritis-and-Chronic-Joint-Pain-Clinical-Trial.pdf
6. Laser Acupuncture Therapy for the Treatment of Tobacco Addiction:
http://theralase.com/wp-content/uploads/2014/05/Smoking-Cessation-Clinical-Study.pdf

26

Research for PDT Division

1. Arenas, Yaxal, Susan Monro, Ge Shi, Arkady Mandel, Sherri McFarland, and Lothar Lilge. 2013. Photodynamic Inactivation of
Staphylococcus Aureus and Methicillin-Resistant Staphylococcus Aureus with Ru(II)-Based Type I/type II Photosensitizers. Photodiagnosis
and Photodynamic Therapy 10 (4): 61525. doi:10.1016/j.pdpdt.2013.07.001.
2. Fong, Jamie, Kamola Kasimova, Yaxal Arenas, Pavel Kaspler, Savo Lazic, Arkady Mandel, and Lothar Lilge. 2015. A Novel Class of
Ruthenium-Based Photosensitizers Effectively Kills in Vitro Cancer Cells and in Vivo Tumors. Photochemical & Photobiological Sciences:
Official Journal of the European Photochemistry Association and the European Society for Photobiology 14 (11): 201423.
doi:10.1039/c4pp00438h.
3. Holder, Alvin A., David F. Zigler, Maria T. Tarrago-Trani, Brian Storrie, and Karen J. Brewer. 2007. Photobiological Impact of
[{(bpy)2Ru(dpp)}2RhCl2]Cl5 and [{(bpy)2Os(dpp)}2RhCl2]Cl5 [bpy=2,2-Bipyridine; dpp=2,3-Bis(2-Pyridyl)pyrazine] on Vero Cells.
Inorganic Chemistry 46 (12): 476062. doi:10.1021/ic0619916.
4. Kaspler, Pavel, Savo Lazic, Sarah Forward, Yaxal Arenas, Arkady Mandel, and Lothar Lilge. 2016. A Ruthenium(ii) Based Photosensitizer
and Transferrin Complexes Enhance Photo-Physical Properties, Cell Uptake, and Photodynamic Therapy Safety and Efficacy.
Photochemical & Photobiological Sciences: Official Journal of the European Photochemistry Association and the European Society for
Photobiology 15 (4): 48195. doi:10.1039/c5pp00450k.
5. Lincoln, Richard, Lars Kohler, Susan Monro, Huimin Yin, Mat Stephenson, Ruifa Zong, Abdellatif Chouai, et al. 2013. Exploitation of LongLived 3IL Excited States for Metal-Organic Photodynamic Therapy: Verification in a Metastatic Melanoma Model. Journal of the American
Chemical Society 135 (45): 1716175. doi:10.1021/ja408426z.
6. Reichardt, Christian, Mitch Pinto, Maria Wchtler, Mat Stephenson, Stephan Kupfer, Tariq Sainuddin, Julien Guthmuller, Sherri A.
McFarland, and Benjamin Dietzek. 2015. Photophysics of Ru(II) Dyads Derived from Pyrenyl-Substitued Imidazo[4,5-f][1,10]phenanthroline
Ligands. The Journal of Physical Chemistry. A 119 (17): 398694. doi:10.1021/acs.jpca.5b01737.

7. Shi, Ge, Susan Monro, Robie Hennigar, Julie Colpitts, Jamie Fong, Kamola Kasimova, Huimin Yin, et al. 2015. Ru(II) Dyads Derived from
-Oligothiophenes: A New Class of Potent and Versatile Photosensitizers for PDT. Coordination Chemistry Reviews 282-283 (January):
12738. doi:10.1016/j.ccr.2014.04.012.
8. Stephenson, Mat, Christian Reichardt, Mitch Pinto, Maria Wchtler, Tariq Sainuddin, Ge Shi, Huimin Yin, et al. 2014. Ru(II) Dyads Derived
from 2-(1-Pyrenyl)-1H-imidazo[4,5-f][1,10]phenanthroline: Versatile Photosensitizers for Photodynamic Applications. The Journal of
Physical Chemistry. A 118 (45): 1050721. doi:10.1021/jp504330s.
9. Yin, Huimin, Mat Stephenson, Jordan Gibson, Eric Sampson, Ge Shi, Tariq Sainuddin, Susan Monro, and Sherri A. McFarland. 2014. In
Vitro Multiwavelength PDT with 3IL States: Teaching Old Molecules New Tricks. Inorganic Chemistry 53 (9): 454859.
doi:10.1021/ic5002368.

27

Competitive Analysis
Theralase Therapeutic Laser Comparison vs. Competitors*
Theralase
TLC -2000

Microlight ML830

Erchonia

Quantum

MEDX

Meditech

Wavelength (nm)

905 and 660

830

635

635

785

840

Drive Platform /
FDA Approval

Super Pulse /
NHN

Continuous Wave
/ NHN

Continuous Wave
/ NHN

Continuous Wave
/ ILY

Continuous Wave
/ ILY

Continuous Wave
/ ILY / NHN

Indicated Use

Knee Pain

Hand and Wrist

Pain

Neck and
Shoulder Pain

Heat

Heat

Heat / Rotator
Cuff Tendonitis

Average Power
(mW)

5 X 200 mW
4 x 100 mW

3 X 30 mW

2 X 5 mW

4 X 5 mW

16 X 5 mW

100 X 15 mW

Peak Power
(mW)

100,000 mW

30 mW

10 mW

5 mW

5 mW

15 mW

Total Actual
Tested Power

1400

90

10

20

72

150

Photon Density
Per Laser Diode
(W/cm2)

10,000

0.5

0.5

1.5

Approximate List
Price (USD)

$20,000

$10,000

$14,000

$12,000

$8,000

$30,000

Approximate
cost per mW
(USD)

$15

$112

$1,400

$600

$112

$200

*Information of competitive devices on this slide is derived from generally available sources, while Theralase believes such sources to be accurate, Theralase has not
conducted any independent investigation of such data

28

What is PDT?
Photo Dynamic Therapy (PDT) is a treatment that uses a drug, called a Photo Sensitizer (PS) or
photosensitizing agent, and a particular type of light. When photosensitizers are exposed to a specific
wavelength of light, they produce a form of oxygen that kills nearby cells

Each photosensitizer is activated by light of a specific wavelength. This wavelength determines how
far the light can travel into the body. Thus, doctors use specific photosensitizers and wavelengths of
light to treat different areas of the body with PDT
PDT is used to treat cancer by localizing and penetrating the cellular wall of the cancer cells. Once
inside the cell they produce Reactive Oxygen Species (ROS), a radical form of oxygen which
destroys the cancer cell from the inside out
Two FDA approved PSs are Amino Levulinic Acid (ALA), which is used to treat Actinic Keratosis
(precursor to melanoma) and Photofrin, which is used to treat certain forms of esophageal cancer
(expand on types of cancer)
The current limitation of ALA and Photofrin is that they are porphyrin based PSs that are only able to
be systemically injected and activated by red laser light, limiting their use to various cancers. Photofrin
was approved for bladder cancer in 1993, but has never been used clinically due to the toxicity and
morbidity to the bladder. They also render the patient extremely light sensitive for 30 to 90 days post
treatment
Theralase expects to overcome these limitations with its technology by designing black body PSs
that can be systemically or intravesically installed in the body and activated from Ultaviolet (UV)
laser light (1/100 of an inch) to Near Infrared laser (NIR) light (4 inches). The PS is completely
removed from the body intravesically in 1 hour and systemically in 7 days, dramatically shortening the
time that the patient is light sensitive
Theralase has a patent pending multi-wavelength laser (UV to NIR) to activate its PDCs and a patent
pending Dosimetry Fibre Optic Cage (DFOC) to activate the PDC inside the bladder of the patient

29

Clinical Trial Design

Lead Institution:
Princess Margaret Cancer Centre (PMCC)
Lead Scientific Principal Investigator:
Lothar Lilge Ph.D.
Lead Clinical Principal Investigator:
Girish Kulkarni MD
Title:
A Phase Ib Trial of Intravesical Photodynamic Therapy in Patients with Non-Muscle Invasive Bladder Cancer at High Risk of Progression Who are
Refractory to Therapy with Bacillus Calmette-Guerin (BCG) and Who are Medically Unfit for or Refuse a Cystectomy
Objectives:
Primary: Evaluate the safety of PDT employing TLD1433 and controlled uniform laser light (TLC-3200 System) in subjects with high risk, Ta/T1 or
Tis non-muscle invasive bladder cancer (NMIBC) that are intolerant or refractory to BCG, and who are not candidates or refuse radical
cystectomy
Secondary: Evaluate the pharmacokinetics (PK) of TLD1433
Exploratory: Efficacy of PDT employing TLD1433 and controlled uniform laser light (TLC-3200 System)
Methodology:
Phase Ib, open-label, single-arm, single-center study conducted in Canada. BCG intolerance or refractory disease are defined as inability to
tolerate or failure to achieve a tumour-free state after at least one induction (a minimum of 5 instillations) followed by either a second induction
(a minimum of 5 instillations) or at least 2 maintenance instillations. Subjects experiencing disease relapse within 12 months or less after
finishing the second course of BCG therapy are also considered refractory. 2 phases: In the first phase, 3 subjects will receive PDT (TLC-3200
System) employing 0.35 mg/cm 2 (maximum recommended starting dose) TLD1433. If treatment with the maximum recommended starting
dose does not raise significant safety concerns, as determined by the safety monitoring committee, an additional 6 subjects will receive PDT
with 0.70 mg/cm2 (therapeutic dose) TLD1433
NMIBC PDT Treatment:
Insert catheter into urethra and install PDC into bladder intravesically for 60 minutes to allow localization into bladder cancer cells
Flush bladder three times to remove any non-adhering PDC
Insert rigid cystoscope through urethra into bladder, fill bladder with distilled water, insert fibre optic bundle and activate PDC for 30 minutes
Void bladder to remove destroyed bladder cancer cells

30