May 2014
A bio-pharmaceutical company developing treatments
for hypertension, diabetes , diabetic nephropathy and
metabolic syndrome.
1
Forward-Looking Statements
This document contains forward-looking information pursuant to
applicable securities law. All information that addresses activities or
developments that we expect to occur in the future are forward-looking
statements. Forward-looking statements are based on the estimates and
opinions of management on the date the statements are made. However,
they should not be regarded as a representation that any of the plans or
objectives will be achieved. Actual results may differ materially from those
expressed or implied by the forward-looking information set forth in this
document due to risks and uncertainties affecting the Company, including
access to capital, the successful completion of clinical trials and receipt of
all regulatory approvals. The forward-looking statements in this document
are based on a number of assumptions which may prove to be incorrect,
including assumptions concerning general business and economic
conditions, positive clinical trials and the availability of financing. XORTX
assumes no responsibility to update forward-looking statements in this
document.
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XORTX Company Overview
• XORTX is a bio-pharmaceutical company founded on patents and patent
applications that include US and worldwide rights for the development of uric acid
lowering agents to treat hypertension, diabetic nephropathy, insulin resistance,
metabolic syndrome and diabetes.
• XORTX’s technology has been validated by successful phase II pilot trials in
adolescent hypertension and chronic kidney injury. These trails demonstrated that
when uric acid levels are decreased, clinically meaningful reduction in hypertension
and decrease in progression of chronic kidney injury occurs.
• African Queen Mines Ltd. (TSX-V: AQ) (the “Company”) is acquiring all of the issued
and outstanding securities of XORTX (a private CBCA company with approximately
38 shareholders) in a reverse take-over, by way of a share exchange agreement.
• XORTX will become a wholly-owned subsidiary of the Company, which will change
its name to reflect its new business.
• In connection with or prior to the Closing, the Company will complete a brokered
private placement to raise a minimum CDN $3,000,000 and up to CDN $6,000,000
plus a 20% over-allotment option.
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Chronically increased Serum Uric Acid is a
Multi-modal cause of hypertension.
Uric Acid a Novel Mechanism of Action for Hypertension
1) Uric acid- Decreases Endothelial Nitric Oxide Production
Nakagawa et al, Am J Physiol 2006; 290:F625-631
2) Uric acid- Increases Renin-Angiotensin-Aldosterone Activation
Mazzali et al Hypertension 38:1101-1106, 2001; JASN 2005; 16:35553-3562
3) Uric acid- Increases circulating Insulin concentration
VASOCONSTRICTION
VASOCONSTRICTION
VASOCONSTRICTION
Reaven GM, Lithell H, Landsberg L. N Engl J Med. 1996;334(6):374-381.
4) Insulin in absence during Nitric Oxide
5) Uric Acid induces glomerular - kidney injury
Mazzali et al, AJP Renal Physiol 282:F991, 2002
VASOCONSTRICTION
SALT SENSITIVE
HYPERTENSION
Conclusion: Uric acid can cause
Progressive, Worsening Hypertension
Serum Uric Acid
“Disease Axis”
Non-Clinical Evidence
Serum Uric Acid Causes
“Disease Axis”
Obesity
Clinical Evidence
Lowering Serum Uric Acid . . .
BLOCKS
Weight Gain
Hypertension
Vascular Injury Kidney Injury
Salt Sensitive Hypertension
Insulin Resistance
Diabetes
DECREASES
High Blood Pressure
DECREASES
Renal Injury /Diabetic
Nephropathy
May Decrease
Diabetes /Met Syn
Insulin Resistance
Kidney loss, Blindness,
Ischemic limbs
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The Product Vision: XORLO
New Mechanism of Action: Best “first choice”
for treatment of Early-Stage Hypertension
A Superior Uric Acid
Lowering Agent For
Controlling Blood
Pressure
New formulation
includes proprietary
molecule-Oxypurinol
with additives to
improve bio availability.
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A Solution with Strong Clinical Validation
And Multiple Therapeutic Indications
1. New Onset Hypertension
• 2 Successful Phase II Clinical Trials- Show Uric Acid is a Causative Factor.
• Fieg D, et al, JAMA, 300(8):924:2008
• Soletsky B. and Fieg D., Uric Acid Reduction Rectifies Prehypertension in Obese
Adolescents, Hypertension 60:1148: 2012
2. Prevention of Diabetes/Insulin Resistance
3. Prevention of Diabetic Nephropathy
• 2 Successful Phase II Clinical Trials- Show Uric Acid Drives Injury
• Siu YP, et al., Am J Kidney Dis, 47;1;2006
• Goicoechea, M., et al., Clin J Am Soc Nephrol, 5:1388;2010
XORLO is being developed for the indications of Hypertension
and Diabetic Nephropathy.
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Strong Correlation Between High Blood Pressure
and Increased Serum Uric Acid in Adolescents
Systolic Blood Pressure (mm/Hg)
180
Systolic BP
(mm Hg)
160
R= 0.80
Drug Intervention
140
LifeStyle Change
120
100
Feig D and R Johnson
Hypertension 2003; 42:247252
80
60
1
2
3
4
5
6
7
8
9
10
Serum Uric Acid (mg/dl)
Uric Acid (mg/dl)
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Randomized Independent Phase II Trial Success in
Obese, Hypertensive Adolescents
Randomized trial of 60 obese, pre-hypertensive adolescents, treated for 2
months with Allopurinol to determine effect on blood pressure
Oxypurinol is a metabolic
derivative of Allopurinol.
At 2 Months Allopurinol
significantly decreased:
Uric Acid: -2.4 mg/dL
(p=0.0005)
SBP:
DBP:
(p=0.0001)
(p=0.0002)
-11.8 mmHg
- 9.6 mmHg
> 80% of individuals whose uric acid was
lowered blood pressure was also normalized.
Weight: -3.1 kg
(p=0.039)
(N.B. Placebo Corrected Differences Reported)
Soletsky B. and Fieg D., Uric Acid Reduction Prehypertension in Obese Adolescents, Hypertension 60:1148: 2012
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XORTX Program Milestones (66 Months to NDA)
2014
2015
2016
2017
2019
2018
2020
$6.0 M
$18 M
License / Sell / Series C
XORLO – Early Stage / Type I Hypertension:
FDA mtg. Phase II
PhII
($3.6 M)
Approval
Phase III
Phase III (if necessary)
NDA
($31 M)
($15.2 M)
XORLO –Treatment of Diabetic Nephropathy
Pivotal Phase III
($ XX,XXX,XXX)
XORLO – Treatment of Diabetes/IR/ Met Syn
Pivotal Phase III
XORTX Operations:
($1.2 M/yr)
($1.2 M/yr)
($1.8 M/yr)
($1.8 M/yr)
($1.8 M/yr)
($1.8 M/yr)
($1.8 M/yr)
Patent Portfolio
Comprised of 5 Families
URIC ACID LOWERING AGENTS (UALA)
FDA Approvable Indications:
1- Hypertension: US 7,799,794- Claim Granted “Allopurinol for the treatment of hypertension
CIP: “All UALA for Hypertension” Exp-July 2022
2- Treatment of Diabetes / Insulin Resistance: PCT-Worldwide application “Claims all UALA
for the treatment of insulin resistance.” Granted in US June 2013- Worldwide pending US ExpSept 2028
3- Treatment of Diabetic Nephropathy: PCT-Worldwide application “Claims all UALA for the
treatment of Diabetic Nephropathy” Exp-July 2028
4- Improved Dosing Formulation of Xanthine Oxidase Inhibitor:
“Claims All XOI in dosing formulation for treatment of Hypertension, Insulin Resistance,
Prevention of Diabetes, Prevention of Diabetic Nephropathy” PCT-Worldwide application, ExpMar 2033
5- Treatment of Metabolic Syndrome:
US Patent Application Number 11/995,943 entitled: “Compositions and Methods for Treatment
and Treatment of Hyperuricemia Related Health Consequences” Exp-Jan 2028
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Competitive Analysis: Hypertension
Treats Cause
Cost to
Patient
Lowers
BP
Renal
Concern
1’ Side
Effect
XORLO (UALA)
YES
SUA, RAAS, Insulin
Low
YES ++
None
Rash ~1%
Thiazides (#1)
NO
Low
YES
Known
Worsens Met Syn
RAAS only
Modest
YES
Concern
Dry Cough ~20%
Worsens Met Syn
Contraindicated for hyperuricemia
ACEI (#2)
RAAS = renin-angiotensin-aldosterone system activation
Conclusion
• Niche 1: Only 50% of patient have adequately controlled BP, thus need for new MoA (CDC.gov)
• Niche 2: Physicians first choice- Thiazides are contraindicated further support for new MoA.
(~33% of prescriptions for BP)
• Niche 3: Recent evidence suggests ACEI may worsen kidney function.
• KEY: Treats cause
& does not worsen metabolic syndrome!
• Overall XORLO will be ideal first choice therapy (lower BP and prevent kidney injury)!
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XORLO Target Markets
US Market Size (individuals/year):
• Adolescent Hypertension:
• New Onset Hypertension:
~2.8 million
~63 million
• Treatment of:
• Diabetic Nephropathy:
• Diabetes/ Insulin Resistance:
• Metabolic Syndrome –Fatty Liver
~10 million
~86 million
~10 million
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Strong Management Team
Allen Davidoff, Ph.D., CEO and President
•
•
•
•
Former Co-Founder & CSO of Stem Cell Therapeutics
12 Years Drug Development Experience- Bench to NDA
8 yrs –C Level management experience-CSO, VP- Product Development
2 IND’s – 9 Clinical trials – 1 NDA
Jennifer Toddhunter, CFO
• Current CFO of African Queen Mines.
• Ms. Todhunter has served as VP Financial Administration, and prior to that served as the Finance
Manager of both African Queen Mines and it predecessor , Pan African Mining Corp., since May 2005.
• 14 yrs. experience with public companies, predominantly those in the mining industry.
Irwin Olian, Chairman
• Current Chairman and CEO African Queen Mines Ltd.
• Founder and served as CEO and Chairman of Pan African Mining Corp. until its acquisition by Asia Thai
Mining Co. Ltd. in June 2008.
• Co-founder and principal shareholder of North American Scientific, Inc., a Los Angeles based
manufacturer of radioisotope products for the treatment of prostate cancer.
• Senior Vice President, Investments, with Sutro & Co. Inc., an established investment banking and
brokerage firm in San Francisco.
• He also served as Vice President of Bear Stearns & Co. Inc.
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Strong Management Team (Continued)
Grace Jung, Ph.D., Director Manufacturing and Synthetic Chemistry
• 21 years of experience in drug discovery and development
• Former Senior Director of Research (Chemistry) at Cardiome.
• Led the chemistry team in the discovery of antiarrhythmic vernakalant. Prior to Cardiome, Grace spent 7
years at Boehringer Ingelheim - medicinal chemist- renin inhibitors as antihypertensive drugs.
Brian Mangal, M.Sc., Director Business Development
• 12 years of clinical and regulatory development experience.
• Formerly Director Biostatistics at Cardiome.
• Extensive Clinical , Regulatory and Corporate development experience includes design, analysis and
reporting of over 50 clinical trials, three FDA submissions, one TPD submission, a successful EMEA
submission and numerous interactions with regulatory authorities and large pharma partner accounts.
Alan Moore, Ph.D., Founding Board Member, Executive Consultant : Clinical and Regulatory Affairs
• 27 years pharmaceutical development experience with 23 years of senior management experience in
pharmaceutical R&D with P&G
• Completed 11 investigational new drug ("IND") applications or supplemental IND's, 15 phase I studies, 12
phase II studies, 7 phase III studies and 2 new drug applications. Most recently CEO of BetaStem Inc.
Bob Rieder, President and CEO- EssaPharmaceuticals
• Current Chairman and Former Co-Founder & CEO Cardiome Pharma
• Led successful development of antiarrythmic drug Vernakalant through European Registration &
Partnership
• 25 yrs –C Level management experience-President, CEO, director
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Clinical Advisory Board
Dr. Richard J. Johnson:
Dr. Johnson is Chief of the Division of Renal Diseases and Hypertension at the University of
Colorado. Temple Hoyne Buell and NKF of Colorado Endowed Professor of Medicine Chief, Division
of Renal Diseases & Hypertension University of Colorado Denver. Dr. Johnson is nationally and
internationally renowned for his work on mechanisms of renal injury and progression, including in
glomerulonephritis, diabetes, and hypertension. Recent studies have focused on the pathogenesis
of essential hypertension and the role of subtle renal injury. He has also performed extensive
research on the role of uric acid and fructose in the epidemic of obesity, metabolic syndrome,
diabetes, and hypertension.
Dr. Daniel Fieg:
Dr. Fieg is Director of the Pediatric Hypertension Program and Pediatric Renal Transplant Program
at the University of Alabama, Birmingham. He also serves on the steering/planning committee for
the hypertension studies being conducted by the Pediatric Trials Network.
Dr. William Hiatt:
Dr. Hiatt has successfully led CPC as President since 1996. He is a past Chair of the United States
Food and Drug Administration (FDA) Cardiovascular and Renal Advisory Committee (2003-08) and
currently serves on the Endocrinologic and Metabolic Drugs Advisory Committee. In addition, Dr.
Hiatt is the Novartis Foundation endowed professor for cardiovascular research in the Department
of Medicine, Division of Cardiology, University of Colorado School of Medicine.
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The Future
The current funding will be utilized to plan, develop and carry-out
a Phase II program of FDA clinical trials. This could lead to the
following:
• Licensing Deal (anticipated as early as 2016-2017)
• Acquisition
Recent Comparative Post Phase II deals:
2012- $1.26 Billion , AstraZeneca acquired Ardea
Lead Product: Uric acid lowering agent for Gout
2009- $900 M , Novartis acquired Speedel
Lead Product: Hypertension agent.
Average deal value - $1.1 B
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Potential Pharmaceutical Partners
• Takeda
 Febuxostat
• AstraZeneca  Lesurinad (repurposed drugs 50%)
• GSK
 Allopurinol
• Novartis
 Hypertension
• Merck
 Hypertension
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Brokered Private Placement
$ 3 million to $ 6 million CAD
12 Million Units @ $0.50 per Unit (Each Unit will be comprised of
one common share and one-half of one share purchase warrant
entitling the holder to purchase one additional share at an
exercise price $0.75 for two years.)
Use of Proceeds:
 API manufacturing
 Pre-IND FDA, IND, Phase II protocol
 XORLO Phase II Hypertension Study
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XORTX Pharma Corp.
Proforma Capitalization (Post Merger and Financing)
Shares Outstanding: ~ 41,000,000
Options and Warrants Outstanding: ~ 10,550,000
Offering Price: $0.50 CAD
Market Cap: $ 20.5 M CAD
Management and Insiders approximately 20%
Note: These numbers assume the full $ 6 M financing.
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The XORTX Corporate Highlights
1. KEY Thought Leaders: Dr. Richard Johnson has defined ‘causative’ role of Serum Uric Acid
in hypertension, insulin resistance, diabetes, Diabetic Nephropathy. Dr. Will Hiatt former
FDA head of Cardio-Renal advisory committee and now advises on the XORTX Scientific
Advisory Board.
2. XORTX Controls Intellectual Property Portfolio - claims for five patent families that cover
use of “all uric acid lowering agents” for of Hypertension, Insulin Resistance, Metabolic
Syndrome, Diabetes Prevention.
3. Strong Management Team - experience in early drug development to market approval,
tailored to developing Oxypurinol through New Drug Application (NDA).
4. Lower development costs and faster time to market – pursuing 505(b)(2) FDA Pathway,
targeting hypertension market launch possible in 2019.
5. Four Phase II clinical trials validate IP concept: show clinically meaningful and statistically
significant effects of lowering serum uric on Early-Stage Hypertension & Progressive
Renal Injury.
6. Recent relevant M&A transactions demonstrates market appetite for this therapeutic
space and validates the return on investment opportunity.
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Innovation, Discovery and Practical Solutions for the
Management of Hypertension and the Prevention of
Diabetes and Diabetic Nephropathy
Contact Information:
Dr. Allen Davidoff,
XORTX Pharma Corp.
www.xortx.com
adavidoff@xortx.com
1-403-607-2621
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