2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an...

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Corporate Presentation June 2019 Inhibiting NOX enzymes to treat multiple diseases with high medical need Euronext: GKTX

Transcript of 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an...

Page 1: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Corporate Presentation

June 2019

Inhibiting NOX enzymes to treat multiple diseases with high medical need

Euronext: GKTX

Page 2: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

DisclaimerThis document has been prepared by Genkyotex (the "Company") and is for information and background purposes only.

While the information contained herein has been prepared in good faith, neither the Company, nor its shareholders, directors, officers, agents, employees, or advisors give, havegiven or have authority to give, any representations or warranties (express or implied) as to, or in relation to, the fairness, accuracy, reliability or completeness of the informationin this document, or any revision thereof, or of any other written or oral information made or to be made available to any interested party or its advisers, including financialinformation (all such information being referred to as “Information”), and liability therefor is expressly disclaimed. Accordingly, neither the Company nor any of its shareholders,directors, officers, agents, employees, affiliates, representatives or advisers take any responsibility for, or will accept any liability whether direct or indirect express or implied,contractual, tortuous, statutory or otherwise, in respect of the accuracy or completeness of the Information or for any of the opinions contained herein or for any errors, omissionsor misstatements or for any loss, howsoever arising from this document.

The information and opinions contained in this document are provided as of the date of this document only and may be updated, supplemented, revised, verified or amended,and thus such information may be subject to significant changes. The Company is not under any obligation to update the information or opinions contained herein which aresubject to change without prior notice.

The information contained in this document has not been subject to independent verification and are qualified in their entirety by the business, financial and other informationthat the Company is required to publish in accordance with the rules, regulations and practices applicable to companies listed on the regulated market of Euronext in Paris,including in particular the risk factors and other information in the Company’s Document de référence (Registration Document) registered by the French Autorité des marchésfinanciers (Financial Markets Authority) (the “AMF”) on April 26, 2019 under no. R. 19-014, and in any other periodic report, which are available free of charge on the websites ofthe Company (www.genkyotex.com) and the AMF (www.amf-france.org).

No representation, warranty or undertaking, express or implied, is made as to the accuracy, completeness or appropriateness of the information and opinions contained in thisdocument. The Company, its subsidiaries, its advisors and representatives accept no responsibility for and shall not be held liable for any loss or damage that may arise from theuse of this document or the information or opinions contained herein.

This document contains information on the Company’s markets and competitive position, and more specifically, on the size of its markets. This information has been drawn fromvarious sources or from the Company’s own estimates which may not be accurate and thus no reliance should be placed on such information. Any prospective investors mustmake their own investigation and assessments and consult with their own advisers concerning any evaluation of the Company and its prospects, and this document, or any part ofit, may not form the basis of or be relied on in connection with any investment decision.

This document contains certain forward-looking statements. These statements are not guarantees of the Company's future performance. These forward-looking statements relateto the Company's future prospects, developments and marketing strategy and are based on analyses of earnings forecasts and estimates of amounts not yet determinable.Forward-looking statements are subject to a variety of risks and uncertainties as they relate to future events and are dependent on circumstances that may or may not materializein the future. Forward-looking statements cannot, under any circumstance, be construed as a guarantee of the Company's future performance and the Company’s actual financialposition, results and cash flow, as well as the trends in the sector in which the Company operates, may differ materially from those proposed or reflected in the forward-lookingstatements contained in this document. Even if the Company’s financial position, results, cash-flows and developments in the sector in which the Company operates were toconform to the forward-looking statements contained in this document, such results or developments cannot be construed as a reliable indication of the Company's future resultsor developments. The Company does not undertake any obligation to update or to confirm projections or estimates made by analysts or to make public any correction to anyprospective information in order to reflect an event or circumstance that may occur after the date of this document.

By reading or otherwise accessing this document, you agree to be bound by the foregoing limitations.

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Ph2 PBC highlight the potential of GKT831 as an anti-fibrotic therapy in the liver, lung, skin, kidney and other organs

Genkyotex: Establishing NOX inhibition as a new therapeutic class

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� We discover and develop oral small molecule NOX inhibitors— NOX enzymes are important since they control multiple stress responses pathways simultaneously — Activation of NOX enzymes is key in many multifactorial diseases

� Lead asset GKT831: a potent anti fibrotic oral small molecule currently in Phase 2 testing— JDRF-funded Phase 2 trial in kidney fibrosis (DKD) ongoing— NIH-funded Phase 2 trial in idiopathic pulmonary fibrosis (IPF) to be launched in H1 2019— Further potential in NASH, PSC, and immuno-oncology

� PBC Phase 2 provides clinical evidence of anti-fibrotic activity in liver fibrosis – a reduction of ~3kPa indicating an average of 1 point liver fibrosis improvement

� Partnership with Serum Institute of India Private Ltd valued at up to €150 million + royalties

� Trading on Euronext as GKTX since March 2017— Cash and cash equivalents of €7.3 million as of March 31 2019, cash runway to April 2020

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Seasoned management team with international life sciences experience

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Elias Papatheodorou Chief Executive Officer

� 25 years of experience in biotechnology and multinational companies� Ex- Philip Morris International, The Coca Cola Company, Novosom AG, Medigene AG

and Covagen AG� Covagen was acquired by Janssen Pharmaceuticals, a J&J Company

� Strong track record in fundraising, business & corporate development and licensingtransactions

Philippe WieselChief Medical Officer & EVP

� Lead clinical research programs at Serono’s EU and US offices, including the phase 3program (ex-US) for Raptiva in psoriasis, leading to the first EMA approval of a biologicagent for psoriasis

� Conducted basic research in the laboratories of Professor Edgar Haber at HarvardMedical School, and of Professor Hans Brunner at the Division of Hypertension inLausanne

Alexandre GrassinVP Finance & Administration

� Diverse experiences in Finance with Novartis from 2007-2010 & Alexion from 2010 to2012

� Financial Auditor with KPMG

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Discovery platform delivers broad pipeline in diseases with high medical needGKT831 Phase 2 PBC data support development in multiple fibrotic diseases

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GKT831 - Liver Fibrosis(NOX1/4 inhibitor)

Primary Biliary Cholangitis (PBC)Top-line results published May 2019

GKT831 - Kidney Fibrosis(NOX1/4 inhibitor)

Diabetic Kidney Disease (DKD) in T1D(IIT1 funded by JDRF2 - Trial launched in H2 2017)

GKT831 - Lung Fibrosis(NOX1/4 inhibitor)

Idiopathic Pulmonary Fibrosis (IPF)(IIT funded by US NIH3 - Trial launch H1 2019)

NOX1 inhibitors Preclinical

Novel NOX inhibitors

Vaxiclase Pertussis vaccine (Licensed to SIIPL)

Preclinical Phase 1 Phase 2 Phase 3Program

Discovery

1Investigator initiated trial2 Juvenile Diabetes Research Foundation3 National Institutes of Health

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NOX inhibitors: pathway based medicine addressing validated disease targets

NOX stands for a group of enzymes called NADPH Oxidases

NOX NOX1 NOX2 NOX3 NOX4 NOX5 DUOX1 DUOX2

VALIDATED DISEASE

PATHWAYS

DISEASE PROCESSES

Inflammation Angiogenesis Fibrosis Proliferation

A family of 7 enzymes that amplify multiple signaling pathways

NF-kB PI3K TRPV1 VEGF

NMDA(CNS)

TRPV1 (hearing loss)

TGF-b PDGF RANKL TLR4 NA Thyroid hormone iodination

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We focus on fibrotic diseases by targeting NOX1 and NOX4 with GKT831

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NOX 1 & 4 are major drivers of fibrogenesis in multiple organsNOXs activates pathways such as TGF-b, PDGF, Hedgehog, TLR4, and CCL2

*Sources: Brenner DA, Hepatology 2012, Brenner DA, PLoS One, 2015, Torok N, Free Radic Biol Med, 2012. Torok N, Gastroenterology, 2015; Thannickal V, Science Trans Med, 2014; Gray SP, Circulation, 2013

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Quiescentfibroblast

LIVER INJURY

NOX/ROS

ProliferationHedgehog

PDGF

ContractilityET-1

FibrogenesisTGF-b1

Matrix degradationMMP-2

ChemotaxisTLR4

MCP-1

Retinoid lossPDGF

MCP-1WBC chemoattraction

FIBROSIS

Pathways amplified by NOX1/4

Activated myofibroblast

SteatosisCholestasis

Hep C/HepBAlcohol

FIBROGENIC PATHWAYS

GKT831 downregulates the activation of multiple clinically validated fibrogenic and apoptotic pathways*

LUNG INJURYSmoking

Toxic chemicalsInflammation

RENAL INJURYHyperglycemia

High blood pressureInflammation

LIVER

FIBROSISKIDNEY

FIBROSISLUNG

GKT831

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Fibrosis: ~45% of all deaths in the developed world1

We focus on Key fibrosis markets with GKT831

Source 1: The Journal of Clinical Investigation; Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases; March 2007. Source 2: The global impact of hepatic fibrosis and end-stage liver disease ; Lim YS1,Kim WR.ClinLiver Dis.2008 Nov;12(4):733-46, vii. doi: 10.1016/j.cld.2008.07.007. Source 3: Nalysnyk L., et al. Incidence and Prevalence of Idiopathic Pulmonary Fibrosis: Review of the Literature. Eur Respir Rev. 2012;21(126):355-361. Source 4: HovindP, Tarnow L, Rossing K, et al. Diabetes care 2003;26:1258-64. Source 5: Groop PH, Thomas MC, Moran JL, et al. Diabetes 2009;58:1651-8. Source 6: Diabetes Care, American Diabetes Association, 2014 Jan;37 Suppl 1:S14-80. doi: 10.2337/dc14-S014.

GKT831

Liver fibrosis impacts 300 to 700 million people worldwide2

� 1st product in NASH to be approved based on anti-fibrotic activity in only 23% of patients

� Fibrosis drives transplants and remains the unmet medical need

Idiopathic Pulmonary Fibrosis (IPF) affects 3 million people

worldwide3

� 2 approved products in IPF each with sales around 1 billion USD sales per year

� Pirfenidone to become generic allowing combination strategies

Diabetic Kidney Disease develops in 20% to 40% of all

diabetics6

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Immuno-oncology therapies not as effective in highly

fibrotic tumors

� Cancer associated fibroblasts (CAFs) oppose immunotherapies by shielding tumors from T-cells

� Targeting CAFs with GKT831 restores response to immunotherapies

� Diabetic Kidney Disease (DKD) is the leading cause of end-stage renal disease4

� Affects 14% to 31% of people with type 1 diabetes after 20 years of diabetes5

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� GKT831 - Orally available small molecule (NCE) with nanomolar potency— NOX1 and NOX4 inhibitor with Ki ~ 100nM in membrane assays

— ~12 hour half-life in humans

— Composition of matter protection till 2028/2029 without any extensions

� Rationale for GKT831 in liver fibrosis— NADPH oxidases NOX1 & NOX4 produce ROS and modulate signaling through oxidation of signaling proteins

— NOX1/4 drive multiple inflammatory & fibrogenic pathways (TGFb, PDGF, TLR4, Hedgehog, NF-kB, CCL2,…)

— NOX1 also activates pathways thought to mediate itching, such as TRPV1

— GKT831 shows marked activity in animal models (bile duct ligation, MDR2 KO, STAM, diet-induced NASH, CCL4)

Rationale for NOX1/4 inhibition with GKT831 in inflammatory and fibrotic disorders

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TGFb signalingNOX structure

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Phase 2 trial of GKT831 in patients with PBC – Top-line final results

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GKT831 ideally positioned to complement the anti-cholestatic activity of generically available drugs like UCDA and fibrates

Primary Biliary Cholangitis (PBC):an orphan disease in the large liver fibrosis market

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Source 1 : In Europe, USA and Japan. Boonstra K. et al. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J Hepatol. 2012 May;56(5):1181-8

� Disease overview• Chronic autoimmune liver disease - progressive destruction of bile ducts

• Prevalence of between 2 - 40 cases per hundred thousand-population1

• Women make up about 90% of PBC cases

• Diagnosis based on presence of auto-Abs and elevated markers of cholestasis including alkaline phosphatase (ALP) & gamma glutamyl transpeptidase (GGT)

� Therapy• Current medications mainly target cholestasis and include generic anti-

cholestatic drugs (UDCA and fibrates) and obeticholic acid

� Unmet medical need• Anti-fibrotic agents to delay disease progression and obviate transplant

• Effective agents targeting itching and fatigue to restore quality of life

• Safe, well tolerated therapy suitable for combination with anti-cholestatic therapies (UDCA, fibrates, OCA)

GKT831

Primary Biliary Cholangitis

Inflammation and scar tissue destroy ducts

Normal bile ducts

Gallbladder

Hepatic ductCommon bile duct

Liver

Cystic duct

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� Primary efficacy endpoint: change in GGT at week 24

� Key secondary endpoints: liver stiffness assessed by Fibroscan®, changes in ALP & QoL

� Key eligibility criteria

— ALP ≥1.5XULN & GGT ≥1.5XULN (stratification according to baseline GGT (> or < 2.5XULN)

— On UDCA for ≥ 6 months & stable dose for ≥ 3 months – stable UDCA dose continued throughout 24-week treatment period

— Exclusion of history of cirrhosis with complications or current MELD score ≥ 15

— ALT > 3XULN or total bilirubin > 1XULN

— Prohibited medications: fibrates and obeticholic acid (12-week wash out)

GKT831 was evaluated in a large 24-week Phase 2 trial

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Placebo

GKT831 400mg once a day (OD)

GKT831 400mg twice a day (BID)

Follow up

Follow up

Follow up

111 randomized (initial target 102)

ALP ≥1.5XULNGGT ≥1.5XULN

Inadequate biochemical response to UDCA

Baseline Week 6 Week 24

GKT831

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Liver fibrosis progressively disrupt liver structure and function

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GKT831

F3 F4

Liver fibrosis is the best predictor of long-term outcomes in multiple liver diseases

F1 F2

Page 14: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Non-invasive assessment of GKT831 effect on fibrosis with Fibroscan®In PBC, liver stiffness ≥ 9.6 kPa corresponds to advanced liver fibrosis of ≥F3

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GKT831

Elas

ticity

(kPa

)

• In multiple liver diseases including PBC, NASH and PSC, liver stiffness correlates with the histologic liver fibrosis stage (F0 to F4)1

• In PSC, elevated liver stiffness is associated with adverse disease outcomes, including liver transplant, hepatic complication and death1

• Our pre-defined cutoff value of 9.6 kPa has been extensively validated and used in previous trials1

1Corpechot C et al. Baseline Values and Changes in Liver Stiffness Measured by Transient Elastography Are Associated With Severity of Fibrosis and Outcomes of Patients With Primary Sclerosing Cholangitis. Gastroenterology 2014;146:970–979. Corpechot C et al. Assessment of Biliary Fibrosis by Transient Elastography in Patients With PBC and PSC. Hepatology 2006;43:1118-1124. Park CC et al. Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients with Biopsy-proven Nonalcoholic Fatty Liver Disease. Gastroenterology 2017; 152(3): 598–607.

Liver stiffness is an indicator of liver inflammation, cholestasis and fibrosis

Fibrosis stage

Histologic fibrosis score

Liver stiffness

Page 15: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Phase 2 trial of GKT831 in PBC: Baseline patient characteristics

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GKT831

Baseline characteristics in line with the targeted population of active PBC patients

1 Once daily; 2 Twice daily

Baseline patient characteristics PlaceboGKT831

400mg ODGKT831

400mg BIDALL

N 37 38 36 111

Age (years) 56 (9) 57 (9) 56 (9) 56 (9)

Females (%) 95 79 94 89

Body weight (kg) 73 (15) 73 (13) 70 (16) 72 (15)

UDCA dose (mg/kg) 13.0 (4.1) 15.9 (5.6) 16.4 (10.4) 15.1 (7.3)

Liver stiffness measurement (kPa) 10.7 (7.0) 12.5 (13.7) 8.3 (3.7) 10.7 (9.5)

GGT (IU/L) 227 (200) 242 (167) 242 (181) 237 (182)

ALP (IU/L) 300 (141) 302 (121) 346 (164) 315 (143)

ALT (IU/L) 43 (16) 45 (22) 56 (35) 48 (26)

AST (IU/L) 43 (17) 44 (21) 50 (31) 46 (24)

Total bilirubin (µmol/L) 10.7 (4.3) 11.1 (4.6) 10.4 (4.6) 10.7 (4.5)

hsCRP (mg/L) 4.8 (4.6) 5.8 (5.2) 5.1 (5.1) 5.3 (4.9)

Values expressed as mean (±SD)

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GKT831 400mg BID achieves significant reduction in GGT over 24-week treatment period (p<0.002)

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GKT831

Perc

ent c

hang

e in

GG

T fr

om B

asel

ine

-7%

-12%

GGT reduction statistically significant over 24-week treatment period. Statistical significance observed at interim not achieved at week 24

Treatment duration (week)

Percent changes in GGT (%)

-6.2-7.5

-5.5

-5.2-8.4

-7

-11.8

1.7

-4.5 -4.9

-17

-22

-18.6 -18.7 -19

-30

-25

-20

-15

-10

-5

0

5

10

15

0 2 6 12 18 24

Mean ± SEM

Placebo (n=37)

GKT831 400mg OD (n=38)

GKT831 400mg BID (n=36)

p=NS

p<0.002 400mg BID vs placebo over 24 weeks

p<0.01

Page 17: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Robust GGT reductions in patients with high baseline GGT (≥2.5XULN, n=86)

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GKT831

Perc

ent c

hang

e in

GG

T fr

om

Base

line

to W

eek

24

These results suggest that GKT831 offers superior benefit to patients with more active disease (higher baseline GGT)

Mean ± SEM

-21%

-30

-25

-20

-15

-10

-5

0

-21%

-6%

-14%

Percent changes in GGT (%)

N=27 N=30 N=29

400mgOD

Placebo 400mgBID

p=0.039

Page 18: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

GKT831 400mg BID achieves significant reduction in ALP over 24-week treatment period (p<0.001)

GKT831

PlaceboGKT831

400mg ODGKT831

400mg BID

Response rate for composite endpoint1 5% 18% 25%

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Perc

ent c

hang

e in

ALP

from

Bas

elin

e

Treatment duration (week)

-3.6 -1.4

-0.6 -0.5

-3.1

-5.5

-8.6

-3.9

-7.8-9.7

-13

-16.3-14.6

-15.8

-12.9

-20

-15

-10

-5

0

50 2 6 12 18 24

Percent changes in ALP (%)

p<0.001

1 ALP<1.67XULN, ALP reduction≥15%, TB <ULN

Placebo (n=37)

GKT831 400mg OD (n=38)

GKT831 400mg BID (n=36)

p=0.049

p<0.001 400mg BID vs placebo over 24 weeks

Mean ± SEM

Page 19: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

GKT831 achieved a positive trend in reduction liver stiffness in full population

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GKT831

Perc

ent c

hang

e in

live

r st

iffne

ss a

t Wee

k 24

(%)

Trend seems to be dose dependent. Baseline values are 10.7 for placebo, 12.5 for 400mg OD and 8.3 kPa for 400mg BID

-0.5

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0.5

Abso

lute

cha

nge

in li

ver

stiff

ness

at W

eek

24 (k

Pa)

Percent change in liver stiffness (%) Absolute change in liver stiffness (kPa)

-6

-5

-4

-3

-2

-1

0

1

2

3

4

5 +4%

-5%

+1%

+0.4

+0.1

-0.4

N=32 N=33

N=26N=32 N=33

N=26

400mg ODPlacebo 400mg BID

Median values Median values

Page 20: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

GKT831 achieved clinically meaningful reduction in liver stiffness in patientswith estimated liver fibrosis score of ≥ F3

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GKT831

Patients with baseline liver stiffness < 9.6 kPa

Patients with baseline liver stiffness ≥ 9.6 kPa

0

2

4

6

8

10

12

14

16

0

2

4

6

8

10

12

14

16

Week 24Baseline

Median values Median values

Live

r stif

fnes

s at B

asel

ine

and

wee

k 24

(kPa

)

Placebo(n=18)

400mg OD(n=21)

400mg BID(n=20)

Placebo(n=17)

400mg OD(n=14)

400mg BID(n=14)

Live

r stif

fnes

s at B

asel

ine

and

wee

k 24

(kPa

)

5.7 6.2 6.2 6.37.0 6.8

12.7

14.2 14.113.1

12.2

9.1

Page 21: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

In just 24 weeks of treatment GKT831 achieves average reduction of 3kPa –an estimated one point fibrosis score reduction

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GKT831

Percent change in liver stiffness Absolute change in liver stiffness

400mg OD (n=14)Placebo (n=17) 400mg BID (n=14)

Abso

lute

cha

nge

in li

ver

stiff

ness

at w

eek

24 (k

Pa)

-5

-4

-3

-2

-1

0

1

2

+0.4

-1.9

-2.7

Mean ± SEM

Perc

ent c

hang

e in

live

r st

iffne

ss a

t wee

k 24

(%)

-35

-30

-25

-20

-15

-10

-5

0

5

10

15

+4.2

-5.3

-20.9

Mean ± SEM

p=0.039

GKT831 achieves clinically significant reduction in liver stiffness in PBC patients with elevated liver stiffness

~3 kPa

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GKT831 400mg BID achieves significantly improves Quality of Life domainsincluding fatigue

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GKT831

GKT831 400mg BID improved quality of life across multiple domains important to PBC patients

1 Once daily; 2 Twice daily

PBC-40 questionnaire

PBC-40 QoL domains PlaceboGKT831

400mg OD1

GKT831400mg BID2

p value (400mg BID vs placebo at week 24)

General symptoms 1.1 1.1 -3.7 0.156Itch (Pruritus) -6.8 -11.4 -9.5 0.443Emotional 8.7 4.9 -16.9 0.031Fatigue 2.4 0.3 -9.9 0.027Social 9.3 8.1 -7.7 0.003Cognitive 5.2 16 -1.9 0.332Mean percent changes from Baseline to Week 24 in Quality of Life domains included in the PBC-40 questionnaire.p values for comparison of changes in the 400mg BID dose against placebo are shown.

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GKT831 was safe & well tolerated at all doses over the 24-week treatmentperiod

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GKT831

Excellent safety profile supports combination therapy with generically available anti-cholestatic agents including UDCA and fibrates

PlaceboGKT831

400mg ODGKT831

400mg BIDSAEs 1 0 1AEs 121 119 100AEs leading to patient discontinuation 0 2 2AEs leading to drug interruption 1 1 2Gastrointestinal 22 25 25Infections 24 12 11Skin and subcutaneous tissue 12 15 14Nervous system 12 17 9General disorders 14 6 12Musculoskeletal and connective tissue 10 12 6Investigations 3 7 7Injury, poisoning, procedural complications 4 4 5Respiratory, thoracic, and mediastinal 4 5 4Psychiatric disorders 7 1 0

Incidence of Treatment-Emergent Adverse Events by System Organ Class (top 10 system organ classes ranked according to AE incidence)

Page 24: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Conclusions & Corporate Information

Page 24

Page 25: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Fibroscan data highlight the potential of GKT831 as an anti-fibrotic therapy

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GKT831

• Clinically significant reduction in liver stiffness suggests average of 1-point improvement in liver fibrosis score in just 24 weeks

• GKT831 400mg BID achieved statistically significant reduction in GGT and ALP over 24-week treatment period (p<0.002 and p<0.001, respectively)

• Significant improvement in quality of life domains important to PBC patients and especially fatigue

• Company planning to advance GKT831 into late stage clinical trials in PBC and other fibrotic liver diseases, like NASH and PSC

• JDRF funded Phase 2 diabetic kidney disease (DKD) trial ongoing

• NIH funded Phase 2 idiopathic pulmonary fibrosis (IPF) trial to be launched in the next months

Page 26: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Corporate information

Page 26

§ Stock market information– Markets: Euronext Paris and Euronext Brussels– Number of shares: 8,022,786 (as of Apr. 2019)

§ Cash Position– €7.3 m in Cash & Cash equivalent (31 Mar. 2019)– Cash runway to April 2020

§ Stock codes– Name: GENKYOTEX– Mnemonic: GKTX– ISIN code: FR0011790542

§ Contacts Genkyotex– Elias Papatheodorou – CEO– Alexandre Grassin – VP Finance and

Administration

Tel.: +33 4 80 16 06 07E-mail: [email protected]: www.genkyotex.com

§ Shareholding structure (as at April 26, 2019):

Page 27: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Appendix – Additional Information on Genkyotex

Page 27

Page 28: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Solid IP portfolio with potential of term extensions in the US, Europe and Japan

Composition of matter protection till 2028/2029 without any extensions

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� GKT831 (per se) and its derivatives in treating NADPH related disorders

GKT831

Country Application No. Patent No. Anticipated expiry Type of protection

USA 12/532,336 8,389,518 12.04.2028 Pharmaceutical formulations/use

USA 13/734,205 9,073,919 20.03.2028 Pharmaceutical formulations/use

Europe 08718102.0 2139477 20.03.2028 Pharmaceutical formulations/use

Europe 12187254.3 2545918 20.03.2028 Pharmaceutical formulations/use

Japan 2009-554036 5715340 20.03.2028 Pharmaceutical formulations/use

Japan 2015-050104 6047189 20.03.2028 Pharmaceutical formulations/use

Country Application No. Patent No. Anticipated expiry Type of protection

USA 13/120,440 9,096,588 22.09.2029 NCE/use

USA 14/750,019 Pending - NCE/use

Europe 9787271.7 2344492 22.09.2029 NCE/use

Europe 14190340.1 Pending - NCE/use

Japan 2011-527466 5700837 22.09.2029 NCE/use

Japan 2014-254651 5932008 22.09.2029 NCE/use

� GKT831 (generically) and its derivatives in treating NADPH related disorders

Page 29: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Phase 2 trial in type 1 diabetes-induced kidney disease (DKD)

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GKT831

l 142 T1D DKD patientsl 48-week treatment in up to 15 centers in Australia. Trials

conducted by Baker Heart and Diabetes Institute in Melbourne

l GKT831 200mg BID against matching placebo, twice daily

Trial # patients Design

l Renal function: estimated glomerular filtration rate (eGFR), and cystatin Cl Renal injury: NGAL, KIM-1

l Inflammation: hsCRP, fibrinogen, IL-6

l Metabolomics and lipidomics profilesl Exploratory epigenetics and transcriptomics studies

Phase 2

Secondary endpoint

l Change in urinary albumin to creatinine ratio (UACR), adjusted for baseline

Primary endpoint

The IIT DKD phase 2 trial funded by JDRF is currently recruiting

Sources 1NGAL: neutrophil gelatinase-associated lipocalin; KIM-1: kidney injury marker 1; hsCRP: high sensitivity C-reactive protein; IL-6: interleukin-6; T1D: type 1 diabetes

Page 30: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Initial phase 2 results in diabetic kidney disease (DKD)

� Excellent safety profile up to 200mg BID for 12 weeks— Well tolerated with fewer adverse events than placebo : moderate

to severe AEs 57 vs 15 (p<0.001) n=68/arm

� Primary endpoint: no significant difference on renal outcomes— Possible reasons:

§ Duration of treatment: 12 weeks sufficient for drugs acting on intra-renal hemodynamics, but not to demonstrate direct anti-inflammatory or anti-fibrotic effects

§ Dose

� Secondary endpoints: pharmacological activity demonstrated— Statistically significant reduction in liver enzymes – GGT (p<0.05)— Strong trend for reduction in triglycerides (p=0.066)— Statistically significant reduction in inflammation - hsCRP (p<0.05)— Strong trend for reduction in additional inflammatory markers –

serum amyloid protein A (p<0.08), IL-6 (p=0.2)

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GKT831

� GKT831 significantly reduces the incidence of adverse events

Adverse eventsSeverity Placebo GKT831 Diff.

All 119 69 -42%Mild 62 54 -12%Moderate 44 14 -68%Severe 13 1 -93%

p<0.001 (CMH analysis)

GKT831 significantly improved multiple predefined secondary efficacy endpoints of liver inflammation and injury. Importantly, the study confirmed the favourable safety profile of GKT831

Page 31: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Preclinical studies: over 50 publications in leading peer-reviewed journals

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GKT831

“Inhibition of NOX4 by GKT831 improves inflammation and fibrosis in fast food diet-fed mice. […]”

Hepatocyte NADPH Oxidase 4 Regulates Stress Signaling, Fibrosis, and Insulin Sensitivity During Development of Steatohepatitis in MiceGastroenterology. 2015 Aug;149(2):468-80

“GKT831 treatment led to a reversal of age-associated persistent fibrosis and reduced mortality. […]” in an IPF model

Reversal of Persistent Fibrosis in Aging by Targeting Nox4-Nrf2 Redox ImbalanceSci Transl Med. 2014 Apr 9;6(231):231ra47

“[…] our results demonstrate the potential of the NOX1 and NOX4 inhibitor GKT831, which is currently in phase 2human clinical trials, as an NLRP3 inflammasome inhibitor […]”

NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages Nat Med. 2016 Sep;22(9):1002-12

“GKT831 treatment prevented skeletal muscle oxidation and nitrosylation of RyR1, restored calstabin1 binding andimproved EDL muscle–specific force. […]”

Excess TGF-b mediates muscle weakness associated with bone metastases in miceNat Med. 2015 Nov;21(11):1262-1271

“[…] pharmacological inhibition of NOX4 may have broad applicability for stromal targeting across cancer types. […]”

Targeting the Myofibroblastic Cancer-Associated Fibroblast Phenotype Through Inhibition of NOX4 J Natl Cancer Inst. 2018 Jan 1;110(1)

Page 32: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

GKT831 markedly reduces fibrosis and inflammation in diet-induced NASH modelRobust anti-fibrotic activity despite sustained steatosis

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Reduced inflammation and fibrosis despite sustained steatosis

Fast food diet model of NASH

831 831

831 831

Source: Torok N et al, Gastroenterology 2015

GKT831

GKT831

Page 33: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Source: Victor Thannickal et al., University of Alabama. Science Translational Medicine, 2014

GKT831 reverses fibrosis & improves survival in a model of irreversible lung fibrosisThe bleomycin model conducted in aged mice induces irreversible lung fibrosis

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n = 21-23/group

Start of treatment

Weeks post injury

Body

wei

ght (

g)

Days post injury

p = 0.043

6 weeks post injury

Hydr

oxyp

rolin

e(µ

g/lu

ng)

Perc

ent s

urvi

val

Control Vehicle GKT831

GKTVehicle

GKTVehicle

GKT831

Page 34: 2019.06 GKTX Corp Presentation FINAL - Biotech Agora · Primary Biliary Cholangitis (PBC): an orphan disease in the large liver fibrosis market Page 11 Source 1: In Europe, USA and

Four Phase 1 studies: very good safety and pharmacodynamics (PD) profile

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� No dose limiting toxicity

� No safety signal

� Dose proportional PK up to 900mg/day

� GKT831 is rapidly absorbed after oral dosing(median tmax ~ 1h)

� Mean half-life of parent compound is 8-15 hours

� Minimal renal elimination (<2%)

� Multiple dosing does not affect PK parameters

� Very low probability of DDI* through CYP3A4

� Low variability in PK parameters when taken with meals

GKT831

Pharmacodynamics

0

2

4

6

8

10

Placebo 100mg OD2

300mg OD

400mg BID3

GKT831900mg

OD

Med

ian

chan

ge in

Min

ima

Eryt

hem

a Do

se (m

J/cm

2 )

ROS

(rel

ativ

e flu

ores

cenc

e)

Time after UV (minutes)

UV + GKT831 2 uM

UV + GKT831 0.2 uM

UV + GKT831 20 uM

No UV

UV + vehicle

UV + Trolox

UV + DPI

120000

100000

80000

60000

40000

20000

0 10 20 30 40 50 60 700

� GKT831 reduces ROS production induced by UVB4 in vitro1

� GKT831 is pharmacologically active in healthy subjects

Safety and PK

Single and multiple doses of GKT831 were well-tolerated and pharmacologically active in healthy subjects

• Drug-drug interactions studies • Sources: 1 In vitro studies conducted at StratiCELL for Genkyotex, unpublished; 2 Once-daily; 3 Twice a day; 4Ultra-violet