A Leader Redefining How Kidney Disease is Treated Investor - - PowerPoint PPT Presentation

Non Confidential

A Leader Redefining How Kidney Disease is Treated Investor Presentation – July 2020

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Forward Looking Statements

This document contains forward-looking information pursuant t o applicable securities law. All information that addresses activities or development s that XORTX expect s t o occur in t he future are forward-looking statement s. Forward-looking st at ement s are based on the estimat es and opinions of management on t he date the statement s are

• made. However, t hey should not be regarded as a representation t hat any of the plans or obj ectives will be achieved

as act ual result s may differ materially from t hose expressed or implied by the forward-looking information set forth in this document due t o risks and uncert ainties affecting XORTX, including access t o capital, t he successful completion of clinical t rials and receipt of all regulat ory approvals. The forward-looking st atement s in t his document are based on a number of assumptions which may prove t o be incorrect, including assumptions concerning general business and economic conditions, positive clinical t rials and t he availabilit y of financing. XORTX assumes no responsibilit y t o update forward-looking st at ements in t his document .

Key Highlights

XORTX clinical development stage products target uric acid lowering, which has been shown to have an important clinical effect. Significant global market opportunities.

Focused on developing clinical stage assets to treat kidney disease

Three lead products in development with strong IP and established proof of concept. XRx-008 for Autosomal Dominant Polycystic Kidney Disease (ADPKD) - Orphan Market XRx-101 for Coronavirus infection/ COVID-19 XRx-221 for type 2 Diabetic Nephropathy ( T2DN) – Large Market

Three Proprietary Products

U.S. Phase 2 study of Uric Acid Lowering in type 2 Diabetic Nephropathy Patients; Topline Phase 2a data readout - August 2019

Positive Phase 2a clinical data readout for T2DN and Uric Acid

Expected initiation of a pivotal registration study in Polycystic Kidney Disease within 12 months - potentially under an SPA Expected initiation of a phase 2/3 study in Coronavirus/COVID-19 with 12 Months

Orphan drug

• pportunity in

polycystic kidney disease.

XORTX’ Senior team was responsible for Oxypurinol and Vernakalant development at Cardiome Pharma

Experienced Management Team

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Endothelial NO Depletion Oxidative Stress Activation Renin Angiotensin System Systemic Inflammation

High Blood Pressure Vascular Damage Fibrosis Kidney Inflammation Proteinuria Decline of Filtering Capacity Normalized Blood Pressure Decreased Proteinuria Decrease and Reversal of Decline in Filtering Capacity

Momeni A, Effect of Allopurinol on Decreasing Prot einuria in Type 2 Diabet ic Pat ient s, Int J Kid Dis, 4(128), 2010 Goicoechea et al. (2010) Effect of allopurinol in CKD progression and CV risk. Clin J Am S

• c

Nephrol 5:1388-1393 S

• let sky B et . al., Uric Acid Reduct ion Rect ifies

Prehypert ension in Obese Adolescent s, Hypert ension 2012;60:1148-1156

Xanthine Oxidase and Uric Acid (UA): Injury  Kidney Disease

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High UA Levels Predict Diabetic Nephropathy Lowering UA Protects Kidney Health in Human Clinical Trials

Decreasing Uric Acid levels in Diabetes Patients may delay progression to ESRD and the need for dialysis or transplant

ESRD –A Life Altering Event

• 4 hours per day on dialysis
• Loss of ability to work full time
• Dependence on family
• Pain and declining health are constant burden
• S

hortened survival – only 50%

• f patients survive

two years

• In progressive kidney

disease uric acid hastens loss of filtering capacity of kidneys

• A therapy that maintains

and extends kidney health can redefine kidney disease treatment in the future

S

• urce: Curr Opin Nephrol Hypert ens – 22(2): 185-192, 2013

XORTX Therapies are designed to delay or reverse progression

• f kidney disease, to prevent ESRD

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Patent Claims Term US 9,155,740 Method of use claims covering uric acid lowering agents (Xanthine Oxidase Inhibitors) in the treatment of “ Diabetic Nephropathy” Acid 2025 * * est imat ed GATT ext ension of 4 - 5 years PCT/ US 14/ 30292 Formulations patent covering Xanthine Oxidase Inhibitors: specifically for Oxypurinol (XRx-008) 2034 Prophetic Patent A novel formulation for treatment of co-morbidity and mortality associate with coronavirus infection 2040 Note: Orphan exclusivity adds to product protection in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Strong Patent Protection – Covering all Uric Acid Lowering Agents Use in Progressive Kidney Disease

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CLASS IP ADVANTAGES LIMITATIONS Uricosurics Varied Decrease uric acid absorption/ reuptake Inappropriate: Increase kidney stone formation Uricase Off Patent Acute IV use Cannot be used chronically Xanthine Oxidase Inhibitors Allopurinol Off Patent Decreases UA production and serum uric acid ~2-3 mg/ dL. Well Characterized Acceptable side effect profile Only approved for GOUT Only works well in ~28%

• f individuals

Modest effect (~2-3 mg/ dL) S ide effects: Rash, Liver Enzymes, Kidney Febuxostat 2019 Higher Potency - decreases UA production and serum uric acid ~2-6 mg/ dL Only approved for GOUT and Cancer * Recent FDA Boxed Warning Oxypurinol (free acid) 2034 Decreases UA production ~2-3 mg/ dL Improved tolerability Modest effect Poor Bioavailability XRx-008 2034 Decreases UA production ~2-3 mg/dL Improved tolerability 3X increase in Bioavailability Comparable efficacy to Allopurinol XRx-101 2040 Inhibits Xanthine Oxidase, decreases uric acid production Clean safety profile and improved tolerability None observed to date

Current Agents are Ineffective at Best

Competitive Landscape Analysis - Well Differentiated Compared to Landscape

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XRx-008: A Novel Formulation of Oxypurinol

• XRx-008 - a proprietary formulation of Oxypurinol with 3X increased

bioavailability – wholly owned by XORTX Therapeutics Inc. and developed “ In- house”

• Increased tolerability increases compliance and supports chronic dosing
• Increased bioavailability increases oral dosing range
• Independent Phase 2 clinical trials show Oxypurinol lowers uric acid, improves

vascular function

• Negotiating Phase 3 Registration Trial with FDA and Company also intends to seek

S pecial Protocol Assessment

• XRx-008 - pre-IND work and FDA Investigational New Drug application (IND)

meeting completed, Orphan Drug Designation (ODD) application initiated

• Orphan Drug Classification: ~150,000 U.S

. patients

XRx-008 in Polycystic Kidney Disease (PKD)

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(Han M, et al., Hyperuricemia and Deterioration of Renal function in ADPKD, BMC Nephrol 15:63-2014)

(n=32)

• 9
• 9
• 7
• 7
• 5
• 5
• 3
• 3
• 1
• 1

1 3 5 7

e-GFR R change (ml/min/1. 1.73m 73m^2) ^2)

Time e (yrs rs)

eGFR (ml/min/1. 1.73m 73m^2/ ^2/yr)

PreTx (-1yr) Post Tx (1yr)

• 5
• 5
• 4
• 4
• 3
• 3
• 2
• 2
• 1
• 1

1 2

Chang hange in n Serum um Uric Ac Acid (mg/dL)

Time e (yrs)

Seru rum Uri ric Aci cid ( mg/dL)

PreTx (-1yr) Post Tx (1yr)

p=0.001 p=0.001

Serum uric acid (SUA) concentrations are higher in APDKD patients than

• controls. (Mej ias et al. Hyperuricemia, gout, and

autosomal dominant polycystic kidney disease. Am J Med Sci 1989; 297: 145– 148)

Higher SUA is associated with increased kidney volumes, increased End S tage Renal Disease (ES RD), and ADPKD disease

• progression. (Helal, 2013)

Increased SUA is strongly associated with endothelial dysfunction (ED) via decreased nitric oxide bioavailability.

(Khosla, 2005, Zoccali 2006, Kurowska 2002, Portaluppi 2004)

In early stage ADPKD patients, uric acid levels (p<0.001) and eGFR (p<0.001) predict ED. (Kocygit et al. Clinical Practice, Nephron

Clin Pract 123:157-164, 2013.)

Decreasing uric acid in ADPKD patients reverses the rate of glomerular filtration rate decline. (Han et al.)

Losing ~ -4.5 (ml/min/year) Gains ~ +2.2 (ml/min/year)

Exceeds FDA improvement necessary for approval !

XRx-008 – Uric Acid Lowering in ADPKD Provides Clinically Meaningful Benefit

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Development Timeline: ** Planning to Initiate Pivotal S tudy under S P A in second half of 2020 **

Mfg GMP(9 mont hs) Finalize IND Finalize ODD BA S t udy Prot ocol/ S P A Ph III Ph3 Pivotal Study under SPA - (30 months) NDA filing

(Accelerated Review)

Marketing Approval

2020 2021 2022 2023 2024 2025

GMP - Good Manufacturing Process Standards IND - Investigational New Drug ODD - Orphan Drug Designation BA - Bio-availability Study in Man SPA - Special Protocol Assessment NDA - New Drug Application for marketing

XRx-008 –Autosomal Dominant Polycystic Kidney Disease (ADPKD)

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XRx-101 –A Novel Formulation of Oxypurinol for the treatment of COVID-19 / Coronavirus

• XRx-101 - a proprietary formulation of

Oxypurinol designed inhibit xanthine oxidase, inhibit oxygen radical and uric acid production, ameliorate kidney injury associated with COVID- 19 infection.

• Current evidence suggests anti-viral effects

Akaike et al, 1990; El-Farrash et al, 2003

• Xanthine oxidase inhibition suppressed influenza

symptoms and increases survival in mouse model.

Akaike et al, 1990

• Xanthine oxidase inhibition suppressed herpes

infection in individuals. El-Farrash, et al, 2003

• Viral infection due to influenza increases xanthine
• xidase activity 400 fold in the mouse. Akaike et al, 1990
• Xanthine oxidase expression is increased in adult

respiratory syndrome (S ARS ). Grum et al 1987

• Coronavirus infections are often associated with

increased IL-6, TNF-a and NF KappaB expression and inflammatory inj ury. Liu B et al, 2020; DeDiego ML et al, 2014 &

Dosch S F et al, 2009

• Xanthine oxidase inhibition can decreases IL-6,

TNF-a and block NF Kappa B signaling. 11

XRx-101 – COVID-19 / Coronavirus Infection

COVID-19 Infection

Week 1 2 3 4 5 -->

No S ymptoms Lung S ymptoms2 Viral Pneumonia 2’ Bacterial Pneumonia Fever Rhabdomyolysis Muscle cell lysis1 Inflammatory Cascade/ S torm Escalating Inflammation Accumulating cell components (Uric Acid)1,3 Kidney4 and Multi-organ Failure Death Extended recovery from Lung, Kidney and Multi-organ Fibrosis

Proposed Oxypurinol Effect

80%

• Few sympt oms -- --14%

Hospit alized-- --6%

• Vent ilat ion support -- -- 5%

Dialysis-- -- 1.5% Death Hospitalized-----Respirator--------------------------Dialysis

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• “ Indicates proposed therapeutic effect of xanthine oxidase inhibition
• 1. Gois PHF, et al, Allopurinol attenuates Rhabdomyolysis- Associated Acute Kidney Injury, Free Radic Biol Med, 101:176-189-2016
• 2. Kuipers MT, et al Pretreatment with Allopurinol attenuates barrier dysfuntion in VI lung Injury, PLOS ONE 2012
• 3. Alakel N, et al, Prevention and treatment of tumor lysis syndrome, Onco Targets Ther_10:597-605-2012
• 4. Abu-Alfa AK, et al, Tumor Lysis Syndrome and Acute Kidney Injury, Am J Kid Dis, 55_5_3_S1-s13_2010

Endothelial Dysfunction: Diabetes, Hypertension

XRx-101 for Coronavirus Induced Acute Kidney Disease XRx-101 in Coronavirus Infection Suppression of Viral and Acute Kidney Injury

Opportunity #1a: Orphan Disease – Phase 3

Compassionate use or, Registration Study Initiation 2020 Data Readout 2021 U.S. Marketing Approval TBD ~ Hospitalized Individuals 16,000,000 U.S. ~200,000,000 Individuals Worldwide

A Crisis Driven – Significant Market Opportunity

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Development Timeline: ** Depending on FDA Feedback Compassionate Use or Initiate Pivotal S tudy Q4 of 2020 **

Mfg GMP(7 mont hs) Finalize IND Compassionate use / clinical t rial Finalize ODD BA S t udy Prot ocol/ S P A Ph III Ph3 Pivotal Study (8 months) XRx-101 + other anti-viral(s) NDA filing Clincl & Commrcl Drug supply (Accelerated Review) Marketing Approval

2020 2021 2022 2023 2024 2025

GMP - Good Manufacturing Process Standards IND - Investigational New Drug ODD - Orphan Drug Designation BA - Bio-availability Study in Man SPA - Special Protocol Assessment NDA - New Drug Application for marketing

XRx-101 –A Coronavirus / Acute Kidney Injury Therapy

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Progressive Kidney Disease XRx-221 in Type 2 Diabetic Nephropathy XRx-008 in Autosomal Dominant Polycystic Kidney Disease (ADPDK)

Opportunity #1: Orphan Disease – Phase 3 Opportunity #2: Diabetic Kidney Disease – Phase 2

Phase 2a Topline August 2019 Phase 2b Initiation 2020 Phase 3a Topline Phase 3b Topline August 2024 August 2025 U.S. Market Approval 2027

Two Significant Market Opportunities

Registration Study Initiation 2020 Data Readout 2022 U.S. Marketing Approval 2023 / 2024 ~ 150,000 Individuals U.S. ~1,500,000 Individuals Worldwide ~ 10,000,000 Individuals U.S. ~100,000,000 Individuals Worldwide

Estimated Peak Sales – USA $1.8B/year Worldwide  $4B/year Estimated Peak Sales – USA $2.4B/year Worldwide  $5B/year 15

Capital Structure

Market Capitalization ~$13 million Common S hares Outstanding 81,179,118 – 85% tightly held Warrants 18,399,084 Options 2,150,000 Fully-diluted S hares Outstanding 101,728,202 Public Listings Longer term plan for NAS DAQ listing

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Key Takeaways

Scarce Assets Addressing a Large Market Opportunity Strong Intellectual Property Portfolio Initial Data Strongly Positions the Company For Clinical Success Important Interim Data Readouts Experienced Management Team With Significant Expertise in Drug Development

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Non Confidential

Contact Information:

• Dr. Allen Davidoff

adavidoff@ xortx.com or 1-403-455-7727

In 2018 and 2019, XORTX focused

• n program value creation:

1. Advanced and accelerated ADPKD program with FDA 2. Type 2 Diabetic Nephropathy with Teij in Pharma –

• Next Gen molecule
• XORTX – Custodian of TMX-049
• VALIDATION of XORTX path

XORTX is a Company with: a phase 3 program in ADPKD and a phase 2 program in T2DN provides signif icant valuat ion, current ly unrecognized

In 2020 and 2021, XORTX will focus on value recogntion:

1. Investor Relations



Roadshows - North America, EU, US



Market makers 2. Liquidity



Nasdaq listing



Uplisting 3. ADPKD



Manufacture XRx-008



Regulatory Filings



BA S tudy 4. T2DN



Manufacturing



Phase 2a announcement (S ep 2019)



Phase 2b preparations

TRANS ITION Value Creation Value Recognition

Listed Company Lead Program Status Market Cap Products Arena ( ARNA) Phase 2 $ 2.11 B None Akebia Phase 3 (4 readouts) $728.21 M FDA approved Auryxia Allena Pre-Phase 3 $200 M None Diamedica Phase 2 $45 M None DaVita Revenue Dialysis $9.16 B Yes Keryx Acquired by AKEBIA $750M valuation See Akebia Reata Phase 3 (3) Phase 3 $2.11 B Alport Syndrome (CKD) Bardoxalone ADPKD Rockewell Medical (RTMI) Triferic – Fe supplement $183 M Yes Tricida +ve Phase 3: Pre-NDA $1B None

Comparable pre-phase 3 NAS DAQ traded companies:

Action Item Plan for Value Creation / Recognition

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Non Confidential

INVESTOR PRESENTATION

Appendix

• Dr. Allen W. Davidoff,

Ph.D.

James Fairbairn, CPA,

ICD.D

• Dr. Alan Moore,

Ph.D.

Brian Mangal Co-founder, CEO CFO Co-founder, S enior Clinical and Regulatory Consultant Director, Business Development

• 15 years drug

development experience focused on clinical and regulatory program development as senior management in pharmaceutical R&D (two IND applications, two phase 1 studies, seven phase 2 studies, and one NDA

• Former Chief S

cientific Officer, VP Product Development/ co-founder

• f S

tem Cell Therapeutics

• Corp. (now Trillium TRIL:

NAS DAQ and TS X) and S enior S cientist and Head

• f Pharmacology,

Cardiome Pharma Corp.

• 20+ years in senior finance

roles with emerging

• companies. He is a

Chartered Professional Accountant, having

• btained his CPA

designation in 1987 and is an Institute-certified

• Director. James Fairbairn

holds a Bachelor of Arts from the University of Western Ontario. He is a director of several j unior listed companies.

• Extensive clinical

development experience and 23 years of senior management experience in pharmaceutical R&D. During his esteemed career, he has completed 11 investigational new drug (“ IND” ) applications or supplemental IND’ s, 15 phase 1 studies, 12 phase 2 studies, 7 phase 3 studies and two new drug applications. Most recently CEO

• f BetaS

tem Inc.

• 15 years of clinical

development experience was former Director of Biostatistics for Cardiome Pharma Corp, Led Biotmetrix of Cardiome’ s clinical programs. Clinical development experience includes design, analysis and reporting on over 50 clinical trials, three FDA submissions, one TPD submission, a successful EMEA submission. Prior to Cardiome, Bostatistician at Pharmacia/ Pfizer, worked on the successful NDA for Linezolid and numerous successful trials with Celecoxib.

Management Team

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Board of Directors

• W. Bruce Rowlands – Chairman, Audit Committee Member
• Biotechnology and investment banking background
• Former S

enior VP, Lorus Therapeutics, a leading Canadian biotechnology company and VP and Director, Dominick and Dominick S ecurities Canada

• Former Chairman and CEO, Eurocontrol Technics Group Inc., a TS

X Venture Exchange listed company

Allen W. Davidoff, Ph.D. - Co-founder, CEO Bruce Cousins – Director, Audit Committee Member

• Accomplished biopharma industry senior finance and operations executive with experience spanning small, early stage

growth to large, international companies

• S

ignificant public company experience, both TS X and NAS DAQ as well as extensive financing and M&A experience

• Former Executive VP and CFO Arbutus Biopharma Corporation, a Nasdaq listed biotech company and Aspreva

Pharmaceutical Inc. and Worldwide Finance Director, Johnson & Johnson

Paul van Damme – Director, Audit Committee Chair

• Extensive career in industry and finance including senior positions with a number of Canadian and US

public companies

• Biotech industry focus through experience with GlycoDesign, Allelix Pharmaceuticals Inc. including participating in the

sale of Allelix to NPS Pharmaceuticals, Inc.

• Currently Managing Director, WCM Capital

Allan Williams – Director

• 30+ years capital market and public company experience including being instrumental in raising over $250 million in

proj ect capital

• Extensive mergers and acquisitions experience

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Advisory Board

• Dr. Petter Bjornstad, MD - Neprhologist
• Clinical Researcher and Assistant Professor of Pediatrics and Medicine, University of Colorado S

chool of Medicine

• NIH and NDRF funded translational research with a track record of research potential and success
• Authored over 70 peer reviewed manuscripts and several high impact j ournals
• Principal investigator of several ongoing studies related to kidney disease and diabetes
• Dr. Richard J. Johnson Jr., MD - Nephrologist
• Tomas Berl Professor, Division of Renal Diseases and Hypertension, University of Colorado S

chool of Medicine, Anschutz Medical Campus

• Dr. Anjay Rastogi – MD, PhD - Nephrologist
• Anj ay Rastogi, MD PhD is Professor and Clinical Chief of Nephrology at the David Geffen S

chool of Medicine at UCLA, Los Angeles, California. Dr. Rastogi is board certified in Nephrology and has a doctoral degree (PhD) in Pharmacology. He is heavily involved in research and serves as the Director of Nephrology Clinical Research Program, Medical Director

• f the ES

RD | Dialysis Program, and Living Kidney Donor Program. Dr. Rastogi’ s research interests include, Adult PKD, Fabry's Disease, Alport S yndrome and Diabetic Kidney Disease.

• Dr. Federico Maese, MD
• Cardiologist and Clinical Researcher focused on preventative cardiology and prevention of coronary artery disease
• Extensive clinical experience in the management of diabetic patients with insulin resistance, metabolic syndrome and

extensive inflammation

• Dr. Henk E. D. J. ter Keurs, MD, Ph.D.
• Cardiologist, LIBIN Cardiovascular Institute of Alberta

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Effect of Xanthine Oxidase Inhibition in Influenza in Mice

Purpose: Evaluate biochemical parameters of influenza virus lung infection Model: sBALF – influenza virus infected mice Biochemical Characteristics: After infection, mice showed 170x increase in adensine deaminase (ADA) and 400 fold increase in Xanthine Oxidase (XO) activity per volume of alveolar lavage fluid Results:

• XO activity peaked at day six of infection.
• ADA metabolites were increased: inosine, hypoxanthine,

xanthine and uric acid in serum.

• Uric acid treatment improved survival rate of influenza virus

infected mice. Conclusion: Increased nucleotide turnover in influenza virus and oxygen radical generation is a pathogenic principle in influenza virus infection.

Akaike T et al_Dependence on oxygen radical generat ion by XO of Pat hogenesis of Influenza Virus Infect ion in Mice_ J Clin invest _ Volume 85_ March 1990_739

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Figure 4: Catabolic profile of adenosine in s-BALF. On day 2 on day 8 uric acid increases substantially. Figure 6: Therapeutic effect of allopurinol on influenza virus-infected mice. Allopurinol was administered orally every 24 h at 1 mg/ mouse ( ) (n=11) or 2 mg per mouse ( ) (n=11), from days 4-7. Vehicle ( PBS ) alone was given in the same manner to the control group ( ) ( n=14).

Ctrl 1mg

(p=0.04)

2mg

(p=0.01)

Effect of Xanthine Oxidase Inhibition in Influenza in Mice

Uric acid increases substantially as influenza infection progresses. Xanthine oxidase inhibition, greatly increases survival during influenza infection. Xanthine oxidase inhibition represents a potentially important therapy

Akaike T et al_Dependence on oxygen radical generat ion by XO of Pat hogenesis of Influenza Virus Infect ion in Mice_ J Clin invest _ Volume 85_ March 1990_739

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Effect of Xanthine Oxidase Inhibition in Herpes Infection

Purpose: Evaluate effect of XOI on Herpes Infection: duration, severity, recurrence. Model: Humans with Recurrent Herpes labialis (RHL). RHL Characteristics: Recurrence, pain, severity are key issues with RHL given oral allopurinol 3x per day 300 mg for 5 days of treatment. Results:

• XO activity decreased duration of recurrence by 2-4 days

(~25% reduction)

• XO decreased severity of lesions (~30%

reduction)

• XO terminated progression (81.6%

showed aborted lesions) Conclusion: Five days of oral XOI at 300 X T .I.D resulted in decreased recurrence, severity and duration of infection.

El-Farrash et al Allopurinol as a pot ent ial t herapeut ic agent for recurrent herpes labialis_J Med and Dent al S ci_2003

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Oxypurinol –Two Key Properties for Viral Suppression

Oxypurinol has demonstrated anti-viral properties (1,2)

1/ El-Farrash, Youssef JM., and El-Mongy S E., Allopurinol as a pot ent ial t herapeut ic agent for recurrent herpes labialis, J Med Dent S ci, Jun 50(2):147-154 2/ Akaike T et al_Dependence on oxygen radical genreat ion by XO of Pat hogenesis of Influenza Virus Infect ion in Mice_ J Clin invest _ Volume 85_ March 1990_739

In the setting of acute tissue inj ury - Oxypurinol inhibits break down of purine and pyrimidine nucleotides to uric acid, decreasing the production of uric acid and serum uric acid from reaching saturation and crystal formation. Blocks Acute Kidney Inj ury in the setting of active tissue inj ury due to Coronavirus infection.

Elion 1968, Nobel Prize for Rational Design

Oxypurinol inhibits synthesis of purine and pyrimidines (1), suggesting that the supply

• f nucleotides necessary for replication of RNA and DNA and formation of viral particles

may be diminished.

1/ Kelly WN., Wyngaarden JB., Effects of Allopurinol and Oxypurinol on Purine S ynthesis in Cultured Human Cells_J Clin Investigation_49_602_1970

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