Download pdf - Investor Presentation - · PDF fileSpeakers Investor Presentation Page 3 Elias Papatheodorou Chief Executive Officer (Genkyotex) More than 20 years of experience in private and public

Investor Presentation

December 22, 2016

Proposed Strategic Combination betweenGenticel and Genkyotex

Disclaimer

IMPORTANT INFORMATION

This presentation does not constitute and shall not be construed as an offer or the solicitation of an offer to purchase, sell or exchange anysecurities of Genticel. In addition, it does not constitute an offer or the solicitation of an offer to purchase, sell or exchange of securities in anyjurisdiction (including the US and the United Kingdom) in which it would be unlawful or subject to registration or qualification under the laws ofsuch jurisdiction.

In connection with the proposed contribution transaction described in this presentation (the “Contribution”), an information document(Document E) will be submitted to the registration of the Autorité des marchés financiers (“AMF”) prior to the shareholders meeting of Genticelwhich will be convened, at the latest on February 28, 2017, to approve the Contribution. Investors and shareholders are strongly advised to read,when available, the Document E that will be filed by Genticel with the AMF and any other relevant document that may be made public or filedwith the AMF as well as any related amendment if any and/or supplements because they will contain important information. Shareholders andinvestors may obtain free copies of documents filed with the AMF at www.amf-france.org or on the website of the company atwww.genticel.com.

FORWARD-LOOKING STATEMENTS

This presentation contains information and statements that might be deemed forward-looking information and statements with respect toGenticel or Genkyotex, including following and subject to the approval and completion of the projected Contribution. They do not constitutehistorical facts. These information and statements include projections that are based upon certain assumptions and assessments made byGenticel and/or Genkyotex managements in light of their experience and their perception of historical trends, current economic and industryconditions, expected future developments and other factors they believe to be appropriate. Forward-looking statements include statementstypically using conditional and containing verbs such as “expect”, “anticipate”, target”, “plan”, or “estimate”, their declensions and conjugationsand words of similar import.

Although the respective management of Genticel and Genkyotex believes that the forward-looking statements and information are reasonable,Genticel’s shareholders and other investors are cautioned that the completion of such expectations is by nature subject to various risks anduncertainties may of which are difficult to predict and generally beyond the control of Genticel and Genkyotex. These risks could cause actualresults and developments to differ materially from those expressed in or implied or projected by the forward-looking statements. These risksinclude those discussed or identified in the public filings made or to be made by Genticel and Genkyotex with the AMF, including notably in theDocument E that will be published in relation to the Contribution. Such forward-looking statements are not guarantees of future performance.Neither Genticel nor Genkyotex undertakes any obligation to update or revise the forward-looking statements and information except to theextent legally required.

Page 2Investor Presentation

Speakers


Elias Papatheodorou

Chief Executive Officer(Genkyotex)

More than 20 years of experience in private and public biotechnologycompanies as well as in multinational corporations (Philip MorrisInternational, The Coca Cola Company, Covagen AG). At Covagen he wasinstrumental in the closing of a CHF46 million series B round and in thesubsequent sale of Covagen to Jannsen Pharmaceuticals, a J&JCompany.

Strong track record in fundraising, business and corporate developmentand licensing transactions

Philippe Wiesel

Chief Medical Officer(Genkyotex)

Lead clinical research programs at Serono’s EU and US offices, includingthe phase 3 program (ex-US) for Raptiva in psoriasis, leading to the firstEMA approval of a biologic agent for psoriasis

Conducted basic research for over five years in the laboratories ofProfessor Edgar Haber at Harvard Medical School, and of Professor HansBrunner at the Division of Hypertension in Lausanne

Alexandre Grassin

Head of Finance and Administration(Genkyotex)

Diverse experiences in Finance with Novartis from 2007-2010 andAlexion from 2010 to 2012

Financial Auditor with KPMG

Benedikt Timmerman

Founder, Chairman of the Management Board and Chief Executive Officer (Genticel)

More than 25 years of experience in life science companies

Co-founded Genticel with Ludovic de Meeus d'Argenteuil in 2001 underthe name of BT Pharma

Genticel’s strategy to extend its pipeline with promising drug candidates

Context

— Process started in 2014: pipeline extension envisioned BOTH in case of lead candidate success or failure

— July 2016: poor results GTL001 phase 2 accelerated engagement of financial advisor Eumedix to assist in acquisition process

Objective: strategic transaction with the most promising Biotech at right valuation vs growth potential

— 4 step evaluation / elimination process of many opportunities led to selection of Genkyotex

Why Genkyotex ?

— Genkyotex focuses on large pharmaceutical markets with unmet need

— Leader in a new therapeutic class of molecules focused on well-understood pathways

— Clinical milestones of lead assets are within reasonable time horizon (1 to 2 years)

— Significant cash available for the clinical development of the existing assets

— Solid intellectual property position and freedom to operate

— Experienced management team with strong track record in clinical and business development

— Business development opportunities for its products candidates


Innovative biotechnology company developing first-in-class NOX therapies

Genkyotex at a glance


NASH: Nonalcoholic steatohepatitis

Founded in 2006 in Geneva (Switzerland) with a subsidiary in Archamps (France)

Specialized in the development of NOX therapies through orally-active small molecules discovered in-house

2 first-in-class product candidates for 2 large therapeutic areas with unmet medical need:

— GKT831 for fibrotic diseases: phase II in Primary Biliary Cholangitis (PBC) orphan disease to be launched in H1 2017 potential to address other fibrotic diseases like NASH as well as fibrosis in other organs

— GKT771 for inflammatory pain: clinical candidate targeting multiple pain processing and angiogenic pathways

Discovery programs: CNS, Hearing Loss and Oncology

Raised CHF87m to date

Main Investors: Eclosion, EdRIP, Vesalius, Neomed, Biomedinvest & VI Partners

Transaction rationale

Acquisition of Genkyotex by Genticel will result into a solid company with strong development potential

Investor Presentation

Leader in the development of NOX inhibitors

BREAKTHROUGH THERAPEUTIC APPROACH

Fibrosis

Inflammatory pain

MARKET OPPORTUNITY IN HIGH-POTENTIAL

THERAPEUTIC SEGMENTS

A phase 2 drug candidate

2nd drug candidate to enter a phase 1 clinical study

A PIPELINE OF TWO FIRST-IN-CLASS MOLECULES

Genticel: — €12.3m in cash at September 30,

2016— Partnership with Serum Institute of

India with potential milestone payments up to $57m

Genkyotex cash position estimated at CHF15.7m at December 16, 2016

BALANCE SHEET STRENGTH

Page 6

A pipeline of 2 first-in-class product candidates


Fibrosis: Primary biliary cholangitis (PBC)

H1

GKT831 NOX1/4

Inflammatory pain & angiogenesis

GKT771 NOX1

R&D

H2 H1 H2 H1 H2

Phase 2

Phase 1 program with

pharmacodynamics readout

New NOX inhibitors for CNS & hearing loss NOX inhibitor for oncology

2017 2018 2019

Sufficient resources to achieve POC in liver disease, complete the phase I with the second asset and pursue research programs

Use of proceeds


Use of consolidated cash position after the

transaction

R&DPursuit of

research programs

Completion of aphase I study

Completion of the phase II study in PBC

1 2 3

GKT831 GKT771

NOX: a new therapeutic space related to protein oxidation


1960’ 1980’ 2000’

Kinase inhibitors

Ligase and proteasome inhibitors

NOX inhibitors

OXIDATIONUBIQUITINATIONPHOSPHORYLATION

Controlling protein networks:

Multiple pathways Multiple signalling levels

NADPH oxidase

SOHSH

Protein oxidoreductase

Gleevec Velcade

NOX involved in multiple diseases – initial focus is fibrotic diseases

NOX: NADPH Oxidase

NOX NOX1 NOX2 NOX3 NOX4 NOX5 NOX6(DUOX 1)

NOX7(DUOX 2)

PATHWAYS

DISEASE PROCESSES

Angiogenesis Inflammation Fibrosis Proliferation

A family of 7 enzymes that amplify multiple signaling pathways

VEGF PI3K TRPV1 NF-kB

NMDA(CNS)

TRPV1 (hearing loss)

TGFb RAS RANKL TLR4 NA Thyroid hormone iodination


NOX1 and NOX4 are two of the most promising NOX targets

NOX 1 & 4: the two most important NOX targets in fibrosis

*Sources: Brenner DA, Hepatology 2012, Brenner DA, PLoS One, 2015, Torok N, Free Radic Biol Med, 2012


Quiescentstellate cell

INJURY

NOX/ROS

Proliferation

Contractility

Fibrogenesis

Matrix degradationMMP-2

Chemotaxis

Retinoid loss

WBC chemoattraction

Fibrosis

Pathways amplified by NOX1/4

Torok N, Gastroenterology, 2015; Thannickal V, Science Trans Med, 2014; Gray SP, Circulation, 2013

Activated myofibroblast

SteatosisCholestasis

Hep C/HepBAlcohol

PATHWAYS

NOX1 & NOX4 involved in multiple clinically validated fibrosis pathways*

Fibrosis: ~45% of all deaths in the developed world 1

Fibrosis, a severe disease reaching multiple organs

Note: 1 The Journal of Clinical Investigation; Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases; March 2007.

GKT831

Eye

Diabetic macular edema Age-related macular degeneration Glaucoma Dry eye syndrome

Liver

Primary biliary cholangitis (PBC)│Orphan disease Non-alcoholic steatohepatitis (NASH) Primary biliary sclerosis (PSC) │Orphan disease Viral hepatitis Alcoholic steatohepatitis

Gastrointestinal

Crohn’s disease

Reproductive

Infertility

Lung

Idiopathic pulmonary fibrosis│Orphan disease Cystic fibrosis│ Orphan disease Scleroderma│ Orphan disease Refractory asthma COPD

Kidney

Diabetic kidney disease Focal segmental

glomerulosclerosis│Orphan disease

Skin

Scleroderma│Orphan disease Keloids Radiation & burn induced fibrosis


Cancer

Host derived tumor stroma Myelofibrosis

Liver fibrosis impacts 300 to 700 million people worldwide2

Liver Fibrosis: a large market opportunity with high unmet need


Sources: 1(Banini BA, et al. Abstract #46. Presented at: American College of Gastroenterology Annual Scientific Meeting; Oct. 14-19, 2016; Las Vegas, NV.)2The 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.

Liver fibrosis can be caused by a multitude of liver insults: fat accumulation, cholestasis and viruses

Cholestasis (Primary biliary cholangitis, primary sclerosing cholangitis, progressive familial intra-hepatic cholestasis)

Nonalcoholic fatty liver disease and non-alcoholic steatohepatitis (NAFLD and NASH)

— in 2016 NASH has become the leading cause of liver transplant in the US1

— liver cirrhosis is the 6th cause of death in developed countries and the 9th in developing countries2

Viral hepatitis (HBV, HCV)

GKT831

F0 F1 F2 F3 F4

SIGNIFICANT FIBROSIS

SEVERE FIBROSIS

CIRRHOSISMILD

FIBROSISNO

FIBROSIS

Reversible Reversible Reversible Irreversible

A gateway to a large fibrosis market

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

A quicker proof of concept (PoC) in smaller and shorter trials


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

Description

— Chronic autoimmune liver disease leading to the progressive destruction of the bile ducts

— Bile, a fluid produced in the liver, plays a role in digesting food and helps rid the body of worn-out red blood cells, cholesterol and toxins

Prevalence

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

— Women make up about 90% of PBC cases

The disease most often develops during middle age and is usually diagnosed in people between the ages of 35 to 60 years

There appears to be a genetic component to developing PBC

Current treatment

— Current medications only slow disease progression and manage symptoms

GKT831

Primary Biliary Cholangitis

Inflammed Bile DuctsNormal Bile Ducts

Over 30 publications in leading peer-reviewed journals

GKT831: extensive preclinical and clinical programme

Sources: 1 Torok N, UC Davis - Free Radic Biol Med, 2012; D. Brenner, UCSD - Hepatology 2012; 2 D. Brenner, UCD - preliminary results; 3 Stelic Institute, Tokyo - Keystone Fibrosis Symposia 2014;4 N. Torok, UC Davis - Gastroenterology 2015; 5 D. Brenner, UCSD - Hepatology 2012


GKT831

12‐week treatment Indication: diabetic kidney

disease

Phase 2

(136 patients)SAFETY PK PD

Efficacy in secondary endpoints 2015

24-week treatment Indication: PBC To start in H1 2017

Phase 2

(90 patients)SAFETY PK PD Clinical efficacy H2 2018

Preclinical

PBC Models:Bile duct ligation1

MDR2 KO mice2

NASH models: STAM mice3

Fast food diet4

Toxic hepatitis modelCCL4-induced

hepatitis and fibrosis5

Established fibrotic models

Single ascending dose Multiple ascending dose Food effect Drug interaction

Phase 1

(4 studies in 117 healthy subjects)

SAFETYPK / Food effect / Drug interactions

Exploratory PD 2013No dose limiting toxicity or safety signals observed in phase 1

Sources: 1 http://www.nature.com/nm/journal/v21/n11/full/nm.3961.html; 2 http://www.nature.com/nm/journal/v22/n9/full/nm.4153.html 3 www.ScienceTranslationalMedicine.org, 9 April 2014, Vol 6 Issue 231 231ra47; 4 http://www.gastrojournal.org/article/S0016-5085(15)00509-0/abstract

Preclinical studies: publications in leading peer-reviewed journals


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 Mice12 October 2015, www.gastrojournal.org4

Over 30 publications to date

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

Reversal of Persistent Fibrosis in Aging by Targeting Nox4-Nrf2 Redox Imbalance9 April 2014, Science Translational Medicine3

“[…] 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 25 July 2016, Advance online publication2

“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 mice12 October 2015, Advance online publication1

Four Phase I studies: very good safety and pharmacodynamics profile


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

GKT831

900mg OD

Med

ian

ch

ange

in M

inim

a Er

yth

ema

Do

se (

mJ/

cm2)

RO

S (r

elat

ive

flu

ore

sce

nce

)

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

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

Initial phase II results in diabetic kidney disease

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)


GKT831

GKT831 significantly reduces the incidence of adverse events

Adverse events

Severity Placebo GKT831 Diff.

All 119 69 -42%

Mild 62 54 -12%

Moderate 44 14 -68%

Severe 13 1 -93%

p < 0.001 (CMH analysis)

Despite not achieving the primary endpoint, GKT831 significantly improved multiple predefined secondary efficacy endpoints in diabetic kidney disease. Most importantly, results support development in inflammatory and fibrotic indications

Phase 2 trial in orphan liver fibrosis indication: PBC


GKT831

90 PBC patients 24-week treatment Placebo and 2 doses (400 mg once-daily and 400 mg twice a day)

Trial # patients Design

Markers of cholestasis and liver injury (ALP, bilirubin, AST, ALT, CK-18)1

Markers of inflammation (hsCRP, fibrinogen, IL-6)

Markers of liver fibrosis (collagen fragments)

Exploratory liver biopsies in a subset of patients

Phase II

Secondary endpoint

A marker of liver injury (Change in serum Gamma Glutamyl Transferase - GGT)

Primary endpoint

A phase II study to start in H1 2017, with interim results expected in H1 2018 and final results H2 2018

Sources: 1ALP: alkaline phosphatase; AST: aspartate aminotransferase; ALT: alanine aminotransferase; CK-18: cytokeratin-18; hsCRP: high sensitivity C-reactive protein; IL-6: interleukin-6)

GKT831’s mechanism of action includes direct anti-inflammatory and anti-fibrotic effects

A unique positioning within the PBC/NASH competitive environment


GKT831

Steatosis Cholestasis

Most products in development in liver fibrosis indications focus on metabolic or cholestatic pathways

Metabolic / cholestatic Inflammatory / fibrotic

Inflammation Fibrosis

Conatus Pharmaceuticals (licensed to Novartis)

InterceptGenfitTobira

(acquired by Allergan)

A selective NOX1 inhibitor with broad therapeutic potential

GKT771: potential to address multiple pain processing and angiogenic pathways


GKT771

Analgesic

Anti-inflammatory

Anti-angiogenic

Potent, highly selective NOX1 inhibitor

NOX1 plays key role in angiogenesis, inflammation, and Inflammatory pain

GKT771 targets the NGF / TrkA / TRPV1 pain processing pathway: a clinically validated target for pain therapies

GKT771 blocks angiogenesis through the VEGF pathway, a clinically validated anti-angiogenic target

GKT771 shows potent activity in vitro and in vivo models of angiogenesis and inflammatory pain

Combined MoA consistent with therapeutic potential in inflammatory pain, as well as in chronic inflammatory diseases

Further therapeutic potential in oncology, eye diseases, endometriosis and pruritus

Excellent ADME profile

IP protection with NCE/use patent running until 2034

GKT771

Multiple potentially value-creating milestones expected in the next 24 months

Sustained newsflow


Beginning of phase II study

(PBC)

2017

Final Results phase II study

(PBC)

Beginning of the phase I program with pharmacodynamics

readout

Final results phase I program with pharmacodynamics

readout

Beginning of a phase II study

H1

2018

Interim Results phase II study

(PBC)Fibrosis: Primary biliary cholangitis (PBC)

GKT831

Inflammation & pain

GKT771

R&DExpected newsflow from the R&D over the coming 2 years

H2 H1 H2

Terms of the transaction

Transaction type: contribution in kind by the existing shareholders of Genkyotex of 100% of the shares they hold in Genkyotex (on a fully diluted basis) to Genticel pursuant to Article 225-147 of the French Code of commerce

Exchange ratio: Genkyotex’s shareholders will receive 11.8355 newly issued shares of Genticel in remuneration for each contributed share of Genkyotex

Ownership:

— Genticel expected to issue 62,279,975 new shares to Genkyotex’s shareholders so that they will hold 80% of Genticel’sshare capital and voting rights (on a non-diluted basis)

— No shareholder of Genkyotex or Genticel is expected, alone or in concert, to hold or control more than 30% of the shares or voting rights of Genticel

Completion of the transaction subject to certain standard conditions including:

— Filing of an information document (Document E) with the French financial market authority (Autorité des marchésfinancier - “AMF”)

— Favorable reports from contribution appraisers

— Approval by Genticel’s shareholders’ general meeting of the proposed contribution and the issuance of the new shares

— Principal shareholders and certain directors of Genticel representing 51% of Genticel share capital and voting rights have undertaken to vote in favor of the proposed contribution transaction

Governance:

— Elias Papatheodorou will become the CEO of the group while Benedikt Timmerman will resign from his mandate as Chairman of the Management Board and continue to focus on business development


Estimated timetable of the transaction

December 22, 2016:

— Execution of the contribution agreement by Genticel and the shareholders of Genkyotex

February 8, 2017 at the latest:

— Filing of (i) the reports of the court appointed appraisers with the registry of the commercial court of Toulouse in compliance with applicable laws and (ii) registration of an information document (Document E) with the AMF in accordance with article 212-34 of the AMF general regulation

February 28, 2017 at the latest:

— General shareholders’ meeting of Genticel to approve the proposed contribution and decide the issuance of Genticel’s new shares to GenKyotex’s shareholders in remuneration of their contributed shares.


Innovative biotechnology company developing first-in-class NOX therapies

Investment highlights


NASH: Nonalcoholic steatohepatitis

NOX therapy specialist

2 first-in-class product candidates for 2 large therapeutic areas with unmet medical need:

— GKT831 for fibrotic diseases: phase II in Primary Biliary Cholangitis (PBC) orphan disease to be launched in H1 2017

potential to address other fibrotic diseases like NASH as well as fibrosis in other organs

— GKT771 for inflammatory pain: clinical candidate targeting multiple pain processing and angiogenic pathways

Discovery programs: CNS, Hearing Loss and Oncology

Main Investors: Eclosion, EdRIP, Vesalius, Neomed, Biomedinvest & VI Partners

APPENDICES

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

Solid patent protection in key countries


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 22.09.2029 NCE/use

Europe 9787271.7 2344492 22.09.2029 NCE/use

Europe 14190340.1 Pending 22.09.2029 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