A bio-pharmaceutical company developing treatments for hypertension, - - PowerPoint PPT Presentation

May 2014

A bio-pharmaceutical company developing treatments for hypertension, diabetes , diabetic nephropathy and metabolic syndrome.

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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
• pinions of management on the date the statements are made. However,

they should not be regarded as a representation that any of the plans or

• bjectives 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 2) Uric acid- Increases Renin-Angiotensin-Aldosterone Activation 3) Uric acid- Increases circulating Insulin concentration 4) Insulin in absence during Nitric Oxide 5) Uric Acid induces glomerular - kidney injury

VASOCONSTRICTION

Mazzali et al Hypertension 38:1101-1106, 2001; JASN 2005; 16:35553-3562 Nakagawa et al, Am J Physiol 2006; 290:F625-631 Mazzali et al, AJP Renal Physiol 282:F991, 2002

SALT SENSITIVE HYPERTENSION

Reaven GM, Lithell H, Landsberg L. N Engl J Med. 1996;334(6):374-381.

Conclusion: Uric acid can cause Progressive, Worsening Hypertension

VASOCONSTRICTION VASOCONSTRICTION VASOCONSTRICTION

Serum Uric Acid “Disease Axis”

Hypertension Serum Uric Acid Causes “Disease Axis” Salt Sensitive Hypertension Insulin Resistance

Diabetes

Obesity Vascular Injury Kidney Injury Kidney loss, Blindness, Ischemic limbs BLOCKS

Weight Gain

DECREASES

High Blood Pressure

May Decrease

Diabetes /Met Syn Insulin Resistance

DECREASES

Renal Injury /Diabetic Nephropathy

Lowering Serum Uric Acid . . .

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Non-Clinical Evidence Clinical Evidence

The Product Vision: XORLO

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A Superior Uric Acid Lowering Agent For Controlling Blood Pressure New formulation includes proprietary molecule-Oxypurinol with additives to improve bio availability.

New Mechanism of Action: Best “first choice” for treatment of Early-Stage Hypertension

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

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XORLO is being developed for the indications of Hypertension and Diabetic Nephropathy.

Strong Correlation Between High Blood Pressure and Increased Serum Uric Acid in Adolescents

60 80 100 120 140 160 180 1 2 3 4 5 6 7 8 9 10

R= 0.80

Feig D and R Johnson Hypertension 2003; 42:247- 252

Uric Acid (mg/dl) Systolic BP (mm Hg)

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Drug Intervention LifeStyle Change

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

Soletsky B. and Fieg D., Uric Acid Reduction Prehypertension in Obese Adolescents, Hypertension 60:1148: 2012

Oxypurinol is a metabolic derivative of Allopurinol. At 2 Months Allopurinol significantly decreased:

Uric Acid: -2.4 mg/dL (p=0.0005) SBP: -11.8 mmHg (p=0.0001) DBP: - 9.6 mmHg (p=0.0002)

> 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)

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$6.0 M

XORTX Program Milestones (66 Months to NDA)

2014 2015 2016

XORLO – Early Stage / Type I Hypertension:

($15.2 M) Phase II Phase III Phase III (if necessary)

XORLO –Treatment of Diabetic Nephropathy XORTX Operations:

($1.2 M/yr) ($1.2 M/yr) ($1.8 M/yr)

2017 2018

($1.8 M/yr) ($1.8 M/yr)

NDA

XORLO – Treatment of Diabetes/IR/ Met Syn

($31 M) ($3.6 M)

2019

($1.8 M/yr) ($ XX,XXX,XXX) FDA mtg. PhII Approval

2020

$18 M ($1.8 M/yr) Pivotal Phase III Pivotal Phase III License / Sell / Series C

Patent Portfolio Comprised of 5 Families

URIC ACID LOWERING AGENTS (UALA)

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 Exp- Sept 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, Exp- Mar 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

FDA Approvable Indications:

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RAAS = renin-angiotensin-aldosterone system activation

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 ACEI (#2) RAAS only Modest YES Concern Worsens Met Syn Dry Cough ~20%

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Contraindicated for hyperuricemia

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)!

XORLO Target Markets

US Market Size (individuals/year):

• Adolescent Hypertension:

~2.8 million

• New Onset Hypertension:

~63 million

• Treatment of:
• Diabetic Nephropathy:

~10 million

• Diabetes/ Insulin Resistance:

~86 million

• Metabolic Syndrome –Fatty Liver

~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
• f 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

• f 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

• f 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

• ne 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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Contact Information:

Innovation, Discovery and Practical Solutions for the Management of Hypertension and the Prevention of Diabetes and Diabetic Nephropathy

• Dr. Allen Davidoff,

XORTX Pharma Corp. www.xortx.com adavidoff@xortx.com

1-403-607-2621

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