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FINANCE AVENUE 2017

FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

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Page 1: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

FINANCE AVENUE 2017

Page 2: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

DisclaimerThis presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra Pharmaceutical’s clinical trials; its ability tosuccessfully gain regulatory approvals and commercialize products; its ability to successfully advance its pipeline of product candidates; the rate and degree of market acceptance of itsproducts ;and itsabilitytodevelopsales and marketingcapabilities.

Forward looking statements are subject to a number of risks, uncertainties and assumptions. Moreover, Mithra Pharmaceutical operates in a very competitive and rapidly changingenvironment.New risks emerge from time to time. It is not possible for Mithra Pharmaceutical’s management to predict all risks, nor can Mithra Pharmaceutical assess the impact of all factorson itsbusinessor the extent to which any factor,or combination of factors, may cause actual results to differ materially fromthose contained in any forward looking statements it may make. Inlight of these risks, uncertainties and assumptions, the forward looking events and circumstances discussed in this presentation may not occur and actual results could differ materially andadverselyfromthose anticipatedor implied intheforward lookingstatements.

You should not rely upon forward looking statements as predictions of future events. Although Mithra Pharmaceutical believes that the expectations reflected in the forward looking statementsare reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward looking statements will be achieved or occur.Moreover,exceptasrequiredby law,neitherMithraPharmaceuticalnor anyotherperson assumesresponsibility for the accuracyandcompletenessof theforward lookingstatements.Forwardlooking statements in thispresentation represent MithraPharmaceutical’sviewsonly asof the date of thispresentation.MithraPharmaceuticalundertakes no obligation to update or review anyforward lookingstatement, whetheras aresultof newinformation, futuredevelopmentsor otherwise,exceptas requiredby law.

This presentation has been prepared by the management of Mithra Pharmaceuticals. It does not constitute or form part of, and should not be construed as, an offer, solicitation or invitation tosubscribe for, underwrite or otherwise acquire, any securities of Mithra Pharmaceuticals or any member of its group nor should it or any part of it form the basis of, or be relied on in connectionwith, any contract to purchase or subscribe for any securities of Mithra Pharmaceuticals or any member of its group, nor shall it or any part of it form the basis of or be relied on in connectionwithany contractorcommitment whatsoever.

The information included in this presentation has been provided to you solely for your information and background and is subject to updating, completion, revision and amendment and suchinformation may change materially. No person is under any obligation to update or keep current the information contained in this presentation and any opinions expressed in relation thereto aresubject to change without notice. No representation or warranty, express or implied, is made as to the fairness, accuracy, reasonableness or completeness of the information contained herein.NeitherMithraPharmaceuticals noranyotherpersonacceptsany liabilityfor any loss howsoeverarising,directlyor indirectly,fromthispresentationor itscontents.

© 2017 | Mithra Investor Presentation | November 2017 | 1

Page 3: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Mithra: Innovatie in Women’s Health

Expert in Women’s Health, met focus op contraceptie (markt: $22 miljard) en menopauze (markt: $USD 8.6 miljard) - Hernieuwde interesse van ‘Big Pharma’ in domein van vrouwelijke gezondheid- Unieke portfolio rond (1) natuurlijk, potentieel veiliger oestrogeen, E4 en (2) Complex Therapeutics

E4: twee potentiële blockbustersmet lancering mogelijk vanaf 2020 Estelle® - 5de generatie anticonceptiepil (Fase III); Donesta® - volgende generatie menopauze-pil (Fase II)

Mithra CDMO : state-of-the-art ecosysteem voor research, development & manufacturingOntwikkeling van ‘Proof of Concept’ tot lancering, voor eigen portfolioproducten en voor partners

- Unieke portfolio rond (1)natuurlijk, potentieel veiligerestrogen, E4 en (2) ComplexTherapeutics

Expertise in Complex TherapeuticsPipeline van complexe, polymeer-baseerde generische producten (bijv. MyringTM; lancering gepland 2018)

| 2© 2017 | Mithra Investor Presentation | November 2017

Groeistrategie: Partnerships met specialisten in Women’s Health, naast bestaande commerciële portefeuille - Waarde van E4- en Complex Therapeutics-porfolio maximaliseren- Marktleider in anticonceptie in Benelux

Page 4: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Transforming Women’s Health through innovation

| 3© 2017 | Mithra Investor Presentation | November 2017

Expert in Women’s Health, met focus op contraceptie (markt: $22 miljard) en menopause (markt: $USD 8.6 miljard) - Hernieuwde interesse van ‘Big Pharma’ in domein van vrouwelijke gezondheid- Unieke portfolio rond (1) natuurlijk, potentieel veiliger oestrogeen, E4 en (2) Complex Therapeutics

E4: twee potentiële blockbustersmet lancering mogelijk vanaf 2020 Estelle® - 5de generatie anticonceptiepil (Fase III); Donesta® - volgende generatie menopauze-pil (Fase II)

Mithra CDMO : state-of-the-art ecosystem voor research, development & manufacturingOntwikkeling van ‘Proof of Concept’ tot lancering, voor eigen portfolioproducten en voor partners

- Unieke portfolio rond (1)natuurlijk, potentieel veiligerestrogen, E4 en (2) ComplexTherapeutics

Expertise in Complex TherapeuticsPipeline van complexe, polymeer-baseerde generische producten(bijv. MyringTM; lancering gepland2018)

Groeistrategie: Partnerships met specialisten in Women’s Health, naast bestaande commerciële portefeuille - Waarde van E4- en Complex Therapeutics-porfolio maximaliseren- Marktleider in anticonceptie in Benelux

Page 5: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Product Indicatie Fase 1 Fase 2 Fase 3 Volgendemilestone

E4* Estelle® Anticonceptie Fase III resultaten:Q3 2018-Q1 2019

Donesta® Menopauze Fase II resultaten:Q1 2018

*Preklinisch: Neuroprotectie (ODD in neonatale encephalopathie)

PK/PD BioEq Filing Goed-keuring

Volgendemilestone

Complex Therapeutics

Myring™ Anticonceptie(Nuvaring®)

Q1 2018: Indienen MA in US

Zoreline® Kanker(Zoladex®)

H2 2017: 1 & 3 maanden PK

Tibelia® Menopauze(Livial®)

H1 2018: 36-maanden shelf life; lanceringen

Unieke portfolio rond E4 en Complex Therapeutics

| 4© 2017 | Mithra Investor Presentation | November 2017

Page 6: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

| 5© 2017 | Mithra Investor Presentation | November 2017

Transforming Women’s Health through innovation

Expert in Women’s Health , met focus op contraceptie (markt: $22 miljard) en menopause (markt: $USD 8.6 miljard) - Hernieuwde interesse van ‘Big Pharma’ in domein van vrouwelijke gezondheid- Unieke portfolio rond (1) natuurlijk, potentieel veiliger estrogen, E4 en (2) Complex Therapeutics

E4: twee potentiële blockbustersmet lancering mogelijk vanaf 2020 Estelle® - 5de generatie anticonceptiepil (Fase III); Donesta® - volgende generatie menopauze-pil (Fase II)

Mithra CDMO : state-of-the-art ecosystem voor research, development & manufacturingOntwikkeling van ‘Proof of Concept’ tot lancering, voor eigen portfolioproducten en voor partners

- Unieke portfolio rond (1)natuurlijk, potentieel veiligerestrogen, E4 en (2) ComplexTherapeutics

Expertise in Complex TherapeuticsPipeline van complexe, polymeer-baseerde generische producten(bijv. MyringTM; lancering gepland2018)

Groeistrategie: Partnerships met specialisten in Women’s Health, naast bestaande commerciële portefeuille - Waarde van E4- en Complex Therapeutics-porfolio maximaliseren- Marktleider in anticonceptie in Benelux

Page 7: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

E4 (Estetrol)

| 6© 2017 | Mithra Investor Presentation | November 2017

Page 8: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

E4 (Estetrol) –Natuurlijkoestrogenmet uniekpotentieel

1 Kluft C et al., Contraception 2016.; 2 Gerard C et al., Oncotarget 2015;6(19):17621-36.; 3 Visser M et al., Horm Mol Biol Clin Invest. 2012;9:95-103.; 4 Visser M et al., Climacteric 2008;11 Suppl 1:64-8.; 5 Mawet M et al., Eur. J. Contracept. Reprod. Healthcare 2015:1-13.; 6 Apter D. et al., Contraception 2016;94(4):366-73; 7 Abot et al., EMBO 2014: 6 (10)

| 7

E4: ingeboren oestrogeen geproduceerd door menselijke foetusvanaf week 9

Plasmaconcentratie in foetus 12x hoger dan moeder

Potentieel van E4 voor Women’s Health gevalideerd in gerenommeerde wetenschappelijke publicaties1-7

E4-programma’s beschermd door 26 patentfamilies, waaronder syntheseproces tot 2032

© 2017 | Mithra Investor Presentation | November 2017

Page 9: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

E4 (Estetrol) –Uniekeagonistische-antagonistischeMode of Action

Cellen hebben 2 types oestrogeenreceptoren (ERα): op niveau van membraan en nucleus

Afhankelijk van het type cel/weefsel is of de membraanreceptor of de nucleaire receptor actief

E4 werkt anders dan oestrogenen die al op de markt zijn:

• Agonist voor nucleaire receptor: E4 gedraagt zich zoals andere oestrogenen in bot, vagina, endometrium en hart

=> zelfde voordelen als andere oestrogenen

• Antagonist voor de membraanreceptor: E4 blokkeert de oestrogeenreceptor in de borst en heeft neutraal effect op lever

=> unieke werking met potentieel beter risicoprofiel

| 8© 2017 | Mithra Investor Presentation | November 2017

Page 10: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

E4: belangrijke potentiële voordelen vs hormonen op markt

> Beter risicoprofiel wat betreft VTE (veneuze thrombo-embolie): longembolie, bloedklonters

> Beter profiel wat betreft combinatie met andere geneesmiddelen (drug-drug interaction)⁴

> Minimale toename van triglyceriden (belangrijk voor diabetes)5

> Minder pijn/gevoeligheid aan borsten6 and verlaagd risico op kanker in aanwezigheid van E21,2,3

> Uitstekende ‘user acceptability’: controle van gewicht en maandelijkese cyclus, lichameliijk & mental welzijn6,7,8

| 9© 2017 | Mithra Investor Presentation | November 2017

1 Kluft C et al., Contraception. 2016.; 2 Gerard C et al., Oncotarget. 2015;6(19):17621-36.; 3 Visser M et al., Horm Mol Biol Clin Invest. 2012;9:95-103.; 4 Visser M et al., Climacteric. 2008;11 Suppl 1:64-8.; 5 Mawet M et al., Eur. J. Contracept. Reprod. Healthcare 2015:1-13.; 6 Data on file ; 7 Apter D. et al., Contraception. 2016;94(4):366-73; 8 Apter D. et al., Eur. J. Contracept. Reprod. Healthcare 2017; 22:4

Klinische resultaten in > 500 vrouwen wijzen op uitstekend profile wat betreft veiligheid en werking voorEstelle® (anticonceptie) & Donesta® (menopause)

Page 11: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Estelle®

| 10© 2017 | Mithra Investor Presentation | November 2017

Page 12: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

1 Transparency market research 2017. $22bn is total hormonal contraceptive market. The oral contraceptive market stands at $9,6bn. 2 IMS Health Data 3 In the 8 biggest markets: US, France, Germany, UK, Spain, Italy, Belgium & Netherlands. United Nations, Department of Economic and Social Affairs, World Bank4 K. Daniels et al., National Health Statistics report n° 62, 2013

Estelle® for anticonceptie, een markt van $22 miljard1

Autoriteiten, o.a. in Europa en de USA, moedigen innovatie aan in sector via bijv. (gebrek aan) terugbetaling en black box warnings

Generatie Welbevinden Veiligheid

1e & 2e generatie

3e & 4e generatie(bijv. Yaz /Yasmin: peak sales €1.2 miljard;

EE + DRSP)1

Potentieel 5e generatie(E4 + DRSP)

24%gebruikt

alternatievemethodes1

27% gebruikt geenvoorbehoeds-

middel2

30% van vrouwen in VS

gebruikt geen pil doorbezorgdheid over

veiligheid ofwelbevinden4

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© 2017 | Mithra Investor Presentation | November 2017

Page 13: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

EU / Rusland : June 2016 (Resultaten: Q3 2018)

Contraceptievewerking

1,577 vrouwen, leeftijd: 18-50

1,350 vrouwen, leeftijd: 18-35

Substudie: veiligheidendometrium

175 vrouwen, leeftijd: 18-50

Estelle® - Fase III studie – Resultaten in Q3 2018 - Q1 2019Twee multicenter, open-label, single arm studies, 13 cycli

VS / Canada : Sept 2016 (Resultaten: Q1 2019)

Contraceptieve werking 2000 vrouwen, leeftijd: 16-50

1800 vrouwen, leeftijd: 16-35

PK substudie(gewicht, ras, roken, …)

500 vrouwen, leeftijd: 16-50

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Eindpunten

Primair eindpunt:

Contraceptieve werking, gemetendoor Pearl Index (PI)

Secondaire eindpunten: Controle cyclus; veiligheid; welbevinden vrouw, substudie over verschillendepopulaties (USA/Canada), endometriale veiligheid (EU)

(1) From 18 years of age in EU © 2017 | Mithra Investor Presentation | November 2017

Page 14: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Donesta®

| 13© 2017 | Mithra Investor Presentation | November 2017

Page 15: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

6.34.1

2002 2005 2016 2025

Menopauzemarkt (in $ miljard)³,⁴

16

Donesta® voormenopauzeand hormoontherapie(HT; markt: $8.6 miljard)1

> 78%¹ van vrouwen in menopauze heeft symptomen van VMS (‘opvliegers’) - slechts 7.8% krijgt HT²

> Reden: veiligheidsrisico’s (VTE, trombose, borstkanker)

> Geen innovatie in laatste decennium, maar hernieuwde interesse (hormonale & niet-hormonale aanpak)

> Potentieel van HT is $10+ miljard potentieel in 2025

> Donesta®: potentieel veiligere pil voor menopauze

(1) Symphony Health Solutions: “The Hormone Replacement Therapy Market for the Treatment of Menopausal Symptoms in the U.S“ Dec 2013 ; (2) KBC company report Aug 2015 (3) IMS link Q2 2016; (4) Datamonitor 2014; Transparency Market Research 2017

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8.6

Potentiële waardeHuidige waarde

© 2017 | Mithra Investor Presentation | November 2017

Page 16: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Donesta® - Fase IIb studie – Top-line resultaten in Q1 2018

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Studie:> 260 vrouwen (rekrutering afgerond)> Leeftijd: 45 -65> Minstens 7 opvliegers per dag of 50/week> 4 dosissen E4 of placebo gedurende 13 weeks (2.5 – 5 – 10 –

15 mg)

Primair eindpunt:

Minimale effectieve dosis E4 voor opvliegers

Belangrijkste secondaire eindpunten:> Vulvovaginale atrofie (vaginale droogte; VVA)> Vaginale maturatie-index> Vaginale pH> Verandering in Menopause Rating Scale (MRS)> Metabolisme lipiden en glucose> Meting hemostatische variabelen en botdensiteit

Multicenter, gerandomiseerde, dubbelblinde, placebo-gecontroleerde study om de beste dagelijksedosis E4 te selecteren voor behandeling van VMS (‘opvliegers’) in menopauze

© 2017 | Mithra Investor Presentation | November 2017

Page 17: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Transforming Women’s Health through innovation

| 16

Expert in Women’s Health , met focus op contraceptie (markt: $22 miljard) en menopause (markt: $USD 8.6 miljard) - Hernieuwde interesse van ‘Big Pharma’ in domein van vrouwelijke gezondheid- Unieke portfolio rond (1) natuurlijk, potentieel veiliger estrogen, E4 en (2) Complex Therapeutics

E4: twee potentiële blockbustersmet lancering mogelijk vanaf 2020 Estelle® - 5de generatie anticonceptiepil (Fase III); Donesta® - volgende generatie menopauze-pil (Fase II)

Mithra CDMO : state-of-the-art ecosystem voor research, development & manufacturingOntwikkeling van ‘Proof of Concept’ tot lancering, voor eigen portfolioproducten en voor partners

- Unieke portfolio rond (1)natuurlijk, potentieel veiligerestrogen, E4 en (2) ComplexTherapeutics

Expertise in Complex TherapeuticsPipeline van complexe, polymeer-baseerde generische producten(bijv. MyringTM; lancering gepland2018)

Groeistrategie: Partnerships met specialisten in Women’s Health, naast bestaande commerciële portefeuille - Waarde van E4- en Complex Therapeutics-porfolio maximaliseren- Marktleider in anticonceptie in Benelux

© 2017 | Mithra Investor Presentation | November 2017

Page 18: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Expertise in Complex Therapeutics

• Experten in ontwikkeling van complexe en innovatieve polymeer-gebaseerde producten

• Focus op hormonalebehandelingen, met veilige, gecontroleerde release van 1 maand tot 5 jaar

• Als een van weinig bedrijven gespecialiseerd in verschillendetoedieningswijzes(incl. vaginale ring, implantaten, spiraaltjes)

• Ontwikkeling en productie in Mithra‘sCDMO - research, ontwikkeling en gespecialiseerde productie

| 17© 2017 | Mithra Investor Presentation | November 2017

Page 19: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

| 18

Transforming Women’s Health through innovation

Expert in Women’s Health , met focus op contraceptie (markt: $22 miljard) en menopause (markt: $USD 8.6 miljard) - Hernieuwde interesse van ‘Big Pharma’ in domein van vrouwelijke gezondheid- Unieke portfolio rond (1) natuurlijk, potentieel veiliger estrogen, E4 en (2) Complex Therapeutics

E4: twee potentiële blockbustersmet lancering mogelijk vanaf 2020 Estelle® - 5de generatie anticonceptiepil (Fase III); Donesta® - volgende generatie menopauze-pil (Fase II)

Mithra CDMO : state-of-the-art ecosysteem voor research, development & manufacturingOntwikkeling van ‘Proof of Concept’ tot lancering, voor eigen portfolioproducten en voor partners

- Unieke portfolio rond (1)natuurlijk, potentieel veiligerestrogen, E4 en (2) ComplexTherapeutics

Expertise in Complex TherapeuticsPipeline van complexe, polymeer-baseerde generische producten(bijv. MyringTM; lancering gepland2018)

Groeistrategie: Partnerships met specialisten in Women’s Health, naast bestaande commerciële portefeuille - Waarde van E4- en Complex Therapeutics-porfolio maximaliseren- Marktleider in anticonceptie in Benelux

© 2017 | Mithra Investor Presentation | November 2017

Page 20: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Mithra CDMO: State-of-the art platform voorontwikkeling& productie

Gespecialiseerd farmaceutisch ecosystem

Voordelen van CDMO:

> Behouden kwaliteitscontrole, IP en expertise > Onafhankelijkheid van 3e partijen> Bijkomde bron van inkomsten dankzij ontwikkeling en productie voor

(gepartnerde) programma’s

Oplevering van tweede deel in H1 2019:

> H2 2016: R&D faciliteit en productielijn voor polymeren, implantaten, injectables

> Europese GMP (Good Manufacturing Practice) goedkeuring voor MyringTM

(mei 2017); FDA goedkeuring verwacht in H1 2018> H1 2019: Productielijn tabletten

| 19© 2017 | Mithra Investor Presentation | November 2017

Page 21: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

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Transforming Women’s Health through innovation

Expert in Women’s Health , met focus op contraceptie (markt: $22 miljard) en menopause (markt: $USD 8.6 miljard) - Hernieuwde interesse van ‘Big Pharma’ in domein van vrouwelijke gezondheid- Unieke portfolio rond (1) natuurlijk, potentieel veiliger estrogen, E4 en (2) Complex Therapeutics

E4: twee potentiële blockbustersmet lancering mogelijk vanaf 2020 Estelle® - 5de generatie anticonceptiepil (Fase III); Donesta® - volgende generatie menopauze-pil (Fase II)

Mithra CDMO : state-of-the-art ecosystem voor research, development & manufacturingOntwikkeling van ‘Proof of Concept’ tot lancering, voor eigen portfolioproducten en voor partners

- Unieke portfolio rond (1)natuurlijk, potentieel veiligerestrogen, E4 en (2) ComplexTherapeutics

Expertise in Complex TherapeuticsPipeline van complexe, polymeer-baseerde generische producten(bijv. MyringTM; lancering gepland2018)

Groeistrategie: Partnerships met specialisten in Women’s Health, naast bestaande commerciële portefeuille - Waarde van E4- en Complex Therapeutics-porfolio maximaliseren- Marktleider in anticonceptie in Benelux

© 2017 | Mithra Investor Presentation | November 2017

Page 22: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

EU VS Andereterritoria

Estelle® Partnering na Fase III

Brazil Japan & ASEAN

Donesta® Partnering na Fase II

Japan & ASEAN

Myring™Partnering-

discussies

Austria

Partneringdiscussies

Other products(incl. Zoreline® ; Tibelia®)

Partneringdiscussies* Partneringdiscussies Partneringdiscussies

Groeistrategie: Partnerships met specialisten in Women’sHealth

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*Tibelia® distributiepartners: o.a. Gedeon, Mercury, Procare, Campus

© 2017 | Mithra Investor Presentation | November 2017

Page 23: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

HY 2016 HY 2017

Revenues 8.4 12.7

R&D Expenses (16.8) (25.5)

G&A (3.8) (3.9)

Selling expenses (4.5) (2.4)

Operating loss (21.518) (24.416)

* Shareholdership in accordance with transparency declarations received by the company and notified managers’ transactions. Market Cap: € 361m as of November 2017 (Euronext: MITRA)** CEO (François Fornieri) holds warrants for 1,211,100 additional shares of Mithra

30.43%CEO**

18.27%Alychlo/ Mylecke

28 .20% Free Float

2.98% Scorpiaux/Verlsluys BVBA

4.33% OGEO Fund OFP

15.80%Meusinvest

Share capital vanaf August 2017* IFRS P&L en cash balance (in k€, FY vanaf 07/30/2017)**

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OTC producten in Women’s Health: EUR 8.8m

Licenties: EUR 3.9m recognized

Donesta®: Fuji Pharma (EUR 1.5m)

Myring™: Mayne Pharma (US) and Gynial (EUR 2..4m)

Cash flow dankzij stabiele generischebusiness en parterningstrategie

Post-period: Estelle® partnership met Libbs in Braziilië (EUR 20m voorafbetaling)

Financiële informatie

© 2017 | Mithra Investor Presentation | November 2017

FY 2016 HY 2017

Cash & Equivalents 45.8 44.7

Page 24: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

VerderbouwenaaneenuniekWomen’s Health-bedrijf

• Meerdere milestones en productlanceringen op korteen middellange termijn

• Estelle® en Donesta®: vergevorderdeonderzoeksprogramma en potentiële blockbusters op basis van uniek E4-platform

• Verschillende partnerships met leiders op het domeinvan de vrouwelijke gezondheid

• Gespecialiseerde research, development & productiecapaciteitmet de Mithra CDMO

• Gediversifieerd model spreidt risico en maximaliseertwaarde van portfolio

2017

Complex Therapeutics

2018 -2020

Estelle®

Complex Therapeutics

> 2020

Complex Therapeutics

Estelle®

Donesta®

Bijkomende indicaties(bijv. neuroprotectie)

| 23© 2017 | Mithra Investor Presentation | November 2017

Page 25: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Contact Us

Website: investors.mithra.com

MithraMITRA (Euronext)

Rue Saint-Georges 5/74000, Liège

Belgium

François [email protected]

Sofie Van GijselIR [email protected]

| 24© 2017 | Mithra Investor Presentation | November 2017

Page 26: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Thank youinvestors.mithra.com

Page 27: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Appendices

| 26© 2017 | Mithra Investor Presentation | November 2017

Page 28: FINANCE AVENUE 2017 - De Tijd...Disclaimer This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of Mithra

Program Trial Patients Characteristics Objectives Results

Estelle® Phase IIa 109 Healthy premenopausalwomen of childbearing potential

Ovulation inhibitionEffect on liver function (surrogate markers of VTE)

No ovulationOnly slight increase vs EE of SHBG1

plasmatic concentration (surrogate marker of VTE risk)

Estelle® Phase IIb 389 Healthy premenopausalwomen of childbearing potential

Vaginal bleeding profileCycle control

Well controlled bleeding patternIndications of reduced VTE risks

Donesta® Phase Ia 32 Healthy postmenopausal women

Safety and tolerability Fast oral absorptionHalf life +/- 28 hours

Donesta® Phase Ib 49 Healthy postmenopausal women: Hysterectomized & non-hysterectomized

Safety and tolerabilityNumber of hot flushes & sweating

Decrease in number of hot flushesE4 as efficient as 2 mgE2V in decreasing hot flushes

1Sex hormone-binding globulin

E4 – Klinische resultaten in > 500 vrouwen

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Uitstekende resultaten wat betreft veiligheid en werking voorEstelle® (15 mg E4/3mg DRSP) & Donesta® (E4 alone)

© 2017 | Mithra Investor Presentation | November 2017

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Note: Hoogland score is a validated tool to assess ovarian function and evaluate ovulation inhibition, which is assessed by transvaginal ultrasounds (TVUS) monitoring of follicle size and analysis of serum E2 and progesterone levels, and consequently classified according to a 6-point scoring (1 = no ovarian activity; 2 = potential activity; 3 = non-active follicle-like structure (FLS); 4 = active FLS; 5 = luteinised unruptured follicle (LUF); 6 = ovulation).

1 Duijkers et al. 2015, Eur.J. Contracept. Reprod. Healthcare

Evaluation of ovulation inhibition: % of patients scored according to Hoogland score (treatment cycle 3; n= 109 healthy premenopausal women of child bearing age)1

0

20

40

60

80

100

5 mg E4/DRSP(n=17)

10 mg E4/DRSP(n=19)

20 µg EE/3 mgDRSP (Yaz)

(n=20)

5 mg E4/LNG(n=18)

10 mg E4/LNG(n=17)

20 mg E4/LNG(n=18)

No activity Potential activity Non-active FLS Active FLS LUF Ovulation

E4 inhibits ovulation in association with a progestin and allows rapid & complete return to fertility

Estelle® Phase IIa: Not a single ovulation

| 28© 2017 | Mithra Investor Presentation | November 2017

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Low increase in SHBG demonstrating significantly reduced VTE risk as compared to Yaz®1

050

100150200250300350400450

Day 3 Day 3 Day 24 Day 3 Day 24 Follow-up

Change of sex hormone-binding globulin (SHBG)plasma levels, as marker of VTE risk

20µg EE/DRSP (Yaz)(n=20)5mg E4/3 mg DRSP(n=17)10mg E4/3 mg DRSP(n=19)

1 Kluft C et al., Contraception. 2016

Estelle® Phase IIa: Reduced VTE risk profile

| 29© 2017 | Mithra Investor Presentation | November 2017

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0

20

40

60

80

100

E2V/DNG(n=78)

15 mgE4/DRSP

(n=79)

20 mgE4/DRSP

(n=79)

15 mgE4/LNG(n=80)

20 mgE4/LNG(n=77)

Higher rates of withdrawal bleeding

0102030405060708090

100

E2V/DNG(n=78)

15 mgE4/DRSP

(n=79)

20 mgE4/DRSP

(n=79)

15 mgE4/LNG(n=80)

20 mgE4/LNG(n=77)

% o

f sub

ject

s

Unscheduled bleeding / spotting after6 treatment cycles

1 Apter D. et al., Contraception. 2016;94(4):366-73

Estelle® Phase IIb: Dose-finding study shows well-controlled bleeding pattern1

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75)

% o

f sub

ject

s

75)QIairaTMQIairaTM Estelle® Estelle®

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Donesta® Phase Ib: Dose-dependent effect on number of hot flushes

Consistent decrease in the mean number ofhot flushes was observed in all dose groups(49 subjects with 35+ hot flushes per week atscreening)

0

2

4

6

8

10

12

14

2mg E2V 2 mg E4 10 mg E4

Mea

n nu

mbe

r of h

ot fl

ushe

s pe

r da

y (ra

nge)

Screening Day 14 Day 28 Day 56 (follow up)

11.5(5-18)

8(4-16)

6.8(2-14)

1.8(0-5)

9(6-16)

5(2-8)

5.6(5-6)

1.8(0-6)

1.8(0-6)

8.4(2-14)

6.5(1-17) 5

(0-15)

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1 Coelingh Bennink et,al. Menopause. 2017.

Donesta® Phase Ib: Minimal increase of triglycerides, a key marker for coronary heart disease

Elevated triglyceride levels are associated with coronary heart disease

Different dose levels of E4 show minimal impact on triglyceride levels1

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Compound CYP 1A2 CYP 2C9 CYP 2C19 CYP 2D6 CYP 3A4

EE <10 <10 82 <10 45

E2 19 <10 63 <10 <10

E4 <10 <10 <10 <10 <10

% inhibition of cytochrome P450 enzymes

1 Visser M et al., Horm Mol Biol Clin Invest. 2012;9:95-103

Pre-clinical results: Lower risk of drug-drug interaction

Minimal interference with liver cells and drug degradation processNo unwanted inhibition of cytochrome P450, major family of drug degradation enzyme1

| 33© 2017 | Mithra Investor Presentation | November 2017

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1 Yagi E et al., Carcinogenesis. 2001;22(9):1505-10.2 Gerard C et al., Oncotarget. 2015;6(19):17621-36.;3 Visser M et al., Horm Mol Biol Clin Invest. 2012;9:95-103.11 Suppl 1:64-8.

E4: Low carcinogenic potential

Lower carcinogenic potential¹

No production of carcinogenic catechol estrogens metabolites

No stimulation of normal or malignant breast cell growth at therapeutic doses

Anti-estrogenic effects in the presence of E2²,³

In the laboratory, E4 was shown to protect against breast cancer development and to decrease size of already existing tumors

Female rats exposed to DMBA for 8 weeks and receiving E4 in parallel

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E4 Recruitment Estelle®

hemostasis study completed

Recruitment Estelle®

Ph III EU/Russia completed

ODD in neonatal encephalopathy (EMA)

Initiation Estelle®

PK ethnobridgingstudy

Donesta® contract with Fuji Pharma

Recruitment PK substudy in Estelle®

completed

Estelle® contract withLibbs for Brazil

Recruitment Donesta®

Phase II studycompleted

Recruitment Estelle® PhIII US/Canada completed

Estelle® QT evaluation

Results PK study for E4 alone

Results Estelle® hemostasis study

Topline results Donesta® Phase II

Completion of ovarian function inhibition data Estelle® : 15 mg E4/3mg DRSP

Results Estelle®

PK ethnobridgingstudy (Japan)

ComplexTherapeutics

Zoreline® 1 month profile &update reformulation 3 month profile

CDMO CDMO Phase II

Multiple near-term catalystsH1 2017 H2 2017 H1 2018 H2 2018 H1 2019

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Submission US MA Myring™

Q3 2018 (Europe/Russia) – Q1 2019 (US/Canada): Top line results of Estelle®

Phase III studies

FDA GMP approval

Myring™ US/EU MA expected

European GMP approval Myring™

Myring™ EU MA submitted

Myring™ contract with Mayne Pharma (US) and Gynial (Austria)

Tibelia®: agreement Canada

Tibelia®: 36-month shelf life

Tibelia®: approvalCanada

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Advisory boards and clinical collaborations1

> EU and US-based advisory boards of key opinion leaders for both Donesta® and Estelle®

> Endorsement of the major potential of E4, providing strategic guidance on clinical programs

> Clinical collaborations with world renowned leaders in women’s health

NNon-exhaustive list

| 36© 2017 | Mithra Investor Presentation | November 2017