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OBSEVA SA filed this Form 6-K on 03/30/2018
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6-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 6-K

 

 

REPORT OF FOREIGN PRIVATE ISSUER

PURSUANT TO RULE 13a-16 OR 15d-16

UNDER THE SECURITIES EXCHANGE ACT OF 1934

For the Month of March 2018

Commission File Number: 001-37993

 

 

OBSEVA SA

(Translation of registrant’s name into English)

 

 

Chemin des Aulx, 12

1228 Plan-les-Ouates

Geneva, Switzerland

(Address of principal executive office)

 

 

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F:

☒  Form 20-F            ☐  Form 40-F

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):  ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7):  ☐

 

 

 


INCORPORATION BY REFERENCE

This report on Form 6-K shall be deemed to be incorporated by reference into the registration statements on Form F-3, as amended (No. 333-222820 and 333-221462) of ObsEva SA (the “Company”) (including any prospectuses forming a part of such registration statements) and to be a part thereof from the date on which this report is filed, to the extent not superseded by documents or reports subsequently filed or furnished.


EXHIBIT LIST

 

Exhibit

  

Description

99.1    ObsEva SA Corporate Presentation dated April 2018.


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

 

    OBSEVA
Date: March 30, 2018     By:   /s/ Ernest Loumaye
      Name   Ernest Loumaye
      Title:   Chief Executive Officer
EX-99.1

Exhibit 99.1

 

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Matters discussed in this presentation may constitute forward-looking statements. The forward-looking statements contained in this presentation reflect our views as of the date of this presentation about future events and are subject to risks, uncertainties, assumptions, and changes in circumstances that may cause our actual results, performance, or achievements to differ significantly from those expressed or implied in any forward-looking statement. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future events, results, performance, or achievements. Some of the key factors that could cause actual results to differ from our expectations include our plans to develop and potentially commercialize our product candidates; our planned clinical trials and preclinical studies for our product candidates; the timing of and our ability to obtain and maintain regulatory approvals for our product candidates; the extent of clinical trials potentially required for our product candidates; the clinical utility and market acceptance of our product candidates; our commercialization, marketing and manufacturing capabilities and strategy; our intellectual property position; and our ability to identify and in-license additional product candidates. For further information regarding these risks, uncertainties and other factors that could cause our actual results to differ from our expectations, you should read our Annual Report on Form 20-F for the year ended December 31, 2017, as filed with the Securities and Exchange Commission on March 9, 2018 and our other filings it makes with the Securities and Exchange Commission from time to time. We expressly disclaim any obligation to update or revise the information herein, including the forward-looking statements, except as required by law. Please also note that this presentation does not constitute an offer to sell or a solicitation of an offer to buy any securities. This presentation concerns products that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration. It is currently limited by federal law to investigational use, and no representation is made as to its safety or effectiveness for the purposes for which it is being investigated. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.


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Strategic Focus: Large populations with high unmet medical need & limited competition Age 15+ Adolescent & Young Adult Gynecology Oral Contraception Anti-Infectives Pregnancy Supplements OTC / Generics Age 15—Age 49 ObsEva Focus Uterine Fibroids Endometriosis Infertility- ART Preterm Labor Preeclampsia Age 50+ Menopause Menopause Symptoms Hormone Replacement Therapy Osteoporosis Generics / Innovation by Big Pharma


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Unique mix of clinical and operational experience provides in-depth understanding of patient & physician needs Ernest Loumaye, MD, PhD, OB/GYN CEO and Co-founder Tim Adams CFO Jean-Pierre Gotteland, PhD CSO Elke Bestel, MD CMO Ben T.G. Tan, MSc VP Commercial & BD A team of 35+ based in Geneva and Boston, with successful experience in world-wide development and commercialization of women health products ObsEva is listed on The NASDAQ Global Select Market and trades under the ticker symbol “OBSV”


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Robust late-stage pipeline for women’s reproductive health & pregnancy PRODUCT CANDIDATE OBE2109* Oral GnRH receptor antagonist NOLASIBAN Oral oxytocin receptor antagonist OBE022 Oral PGF2α receptor antagonist * Kissei developing for Asia PRECLINICAL    PHASE 1 PHASE 2PHASE 3STATUS & NEXTCOMMERCIAL MILESTONERIGHTS US/EU Phase 2b Endometriosis: EDELWEISS** Data mid-2018Worldwide US/EU Phase 3ex-Asia Uterine Fibroids: PRIMROSE1 & 2 Primary Endpoint Data 2H 2019 EU Phase 3 IVF: IMPLANT2EU***Live birth 4Q 2018 US Phase 3Worldwide IVF: IMPLANT3USInitiation 4Q 2018 EU Phase 2a Preterm Labor: PROLONGInterim DataWorldwide Late 2018 ** Patient recruitment completed *** Week10 pregnancy, primary endpoint met in Feb 2018


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2017 Accomplishments and 2018-19 Expected Milestones     Milestone Timing OBE2109 (Endometriosis): Completed EDELWEISS trial EU/US patient enrollment4Q2017 NOLASIBAN (IVF): Completed IMPLANT2 trial recruitment 3Q2017 OBE022 (Preterm labor): Initiate Phase 2a PROLONG proof-of-concept clinical trial 4Q2017 NOLASIBAN (IVF): IMPLANT2 Phase 3 primary endpoint data 1Q2018 OBE2109 (Endometriosis): Phase 2b EDELWEISS 12 week primary endpoint data (pain)Mid-2018 NOLASIBAN (IVF): Live birth rate (LBR) results from IMPLANT2 trial4Q 2018 NOLASIBAN (IVF): Initiation of IMPLANT3 Trial in the U.S.4Q2018 OBE2109(Endometriosis): Phase 2b EDELWEISS 24 week BMD safety results4Q2018 OBE2109(Uterine Fibroids): Enrollment completion in Phase 3 PRIMROSE 1 and 2 trials4Q2018 OBE022 (Preterm labor): Phase 2a PROLONG interim dataLate 2018 OBE2109(Endometriosis): Initiation of Phase 3 Clinical Trial ProgramLate 2018/early 2019 NOLASIBAN (IVF): 6 month baby follow-up from IMPLANT2 trial2Q2019 OBE2109(Uterine Fibroids): Phase 3 PRIMROSE 1 and 2 , 24 week primary endpoint data2H 2019 US Phase 3 IMPLANT3 primary endpoint data (Ongoing Clinical Pregnancy 10 weeks)4Q2019 NOLASIBAN (IVF): Target EU MAA regulatory submission2H 2019


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2017 Accomplishments and 2018-19 Expected Milestones                     Milestone                 Timing     OBE2109 (Endometriosis): Completed EDELWEISS trial EU/US patient enrollment                 4Q 2017    NOLASIBAN (IVF): Completed IMPLANT2 trial recruitment                 3Q 2017    OBE022 (Preterm labor): Initiate Phase 2a PROLONG proof-of-concept clinical trial     4Q 2017    NOLASIBAN (IVF): IMPLANT2 Phase 3 primary endpoint data                 1Q 2018    OBE2109 (Endometriosis): Phase 2b EDELWEISS 12 week primary endpoint data (pain)     Mid-2018    NOLASIBAN (IVF): Live birth rate (LBR) results from IMPLANT2 trial                 4Q 2018    NOLASIBAN (IVF): Initiation of IMPLANT3 Trial in the U.S.                 4Q 2018    OBE2109 (Endometriosis): Phase 2b EDELWEISS 24 week BMD safety results                 4Q 2018    OBE2109 (Uterine Fibroids): Enrollment completion in Phase 3 PRIMROSE 1 and 2 trials 4Q 2018    OBE022 (Preterm labor): Phase 2a PROLONG interim data                 Late 2018 OBE2109 (Endometriosis): Initiation of Phase 3 Clinical Trial Program                 Late 2018/early 2019 NOLASIBAN (IVF): 6 month baby follow-up from IMPLANT2 trial                 2Q 2019    OBE2109 (Uterine Fibroids): Phase 3 PRIMROSE 1 and 2 , 24 week primary endpoint data 2H 2019    US Phase 3 IMPLANT3 primary endpoint data (Ongoing Clinical Pregnancy 10 weeks)                 4Q 2019    NOLASIBAN (IVF): Target EU MAA regulatory submission                 2H 2019


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OBE2109 for Endometriosis and Uterine Fibroids


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OBE2109: Potential best-in-class, oral, GnRH receptor antagonist OBE2109 AT-A-GLANCE • GnRH ReceptorAntagonist • OBE2109 (KLH-2109) • Licensed from Kissei (WW rights, excludesAsia) • IP Protection* to 2036 (COM 2032) • > 1400 female subjects exposed to date OBE2109 INDICATIONS • Uterine Fibroids • Symptoms: Heavy menstrual bleeding and abdominal pain • Primary goal is to reduce/eliminate bleeding • Endometriosis • Symptoms: pain and infertility • Primary goal is to alleviate pain Landscape Standard of Care:    Esmya/Fibristal® Elagolix Relugolix Lupron, SPRM approved in EU/Canada(AbbVie/Neurocrine) in Phase 3 (Myovant/Takeda) in oral contraceptives, surgery for uterine fibroids, U.S. NDADevelopment for fibroids, U.S. NDAPhase 3 Development submittedsubmitted for endometriosis * Including PTA/PTE (Patent Term Adjustment / Patent Term Extension)


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Unmet medical need in endometriosis & uterine fibroids therapy LARGE U.S. MARKET SIZE Uterine Fibroids 4 MILLION WOMEN diagnosed and treated annually ~200K Surgeries (Hysterectomy) Annually Endometriosis 2.5 MILLION WOMEN diagnosed and treated annually Seeking to unlock Another 2.5 MILLION Undiagnosed due to non-specific symptoms and invasive laparoscopy OLDER, SUBOPTIMAL EXISTING TREATMENTS LUPRON® INJECTIONS cause flares, initial worsening of symptoms, no titration possible, prolonged and variable reversibility time ORAL CONTRACEPTIVE and progestin, only partially effective, safety risks SURGICAL INTERVENTIONS costly, invasive, side effects


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GnRH antagonist MoA: Finding a balance between level of estradiol suppression, associated symptoms, and BMD protection High dose GnRH antagonist & add-back Moderate dose GnRH antagonist & no add-back BMD: Bone mineral density ESSS: Endometriosis symptom severity score • Estradiol measured at 1-2 months after treatment initiation was shown to be a reliable predictor of 6-month BMD change. • Estradiol range between 20 and 60 pg/mL targets optimal treatment of endometrial pain while minimizing BMD effects. • This treatment approach will require use of add-back hormone replacement therapy only as needed. Integrated Pharmacometrics and Systems Pharmacology Model-Based Analyses to Guide GnRH Receptor Modulator Development for Management of Endometriosis Riggs MM et al. 2012 CPT: Pharmacometrics & Systems Pharmacology 1, e11.


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OBE2109 suppressed estradiol levels to the target range and reduced endometriosis-related pelvic pain severity across the three Phase 2 clinical trials (no add back) KLH1202 TRIAL: % OF PATIENTS AT VARIOUS ESTRADIOL LEVELS IN KLH1202 TRIAL AT WEEK 12 KLH1202 TRIAL: AVERAGE CHANGE IN SEVERITY OF PELVIC PAIN OVER TIME (MENSTRUAL AND NON-MENSTRUAL PAIN    COMBINED) OBE2109 50 mg OBE2109 100 mg OBE2109 200 mg 0 Placebo Pain Pelvic of y -0.5 Severit *** e *** * *** * *** p < 0.05* ** Averag ** p < 0.01** Δ *** p < 0.001*** Two sample t -test ** vs Placebo -1 Pretreatment Week 4 Week 8 Week 12 Post-treatment    Time (Weeks) (Week 4)


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OBE2109 Phase 2b clinical trial (EDELWEISS) in endometriosis patients Primary endpoint: VRS pain score responder rate 8–14 weeks LEAD-IN 12 weeks Placebo 50 mg daily 75 mg daily 100 mg daily 200 mg daily 75 mg daily* Mid 2018 Key secondary endpoint: BMD 12 weeks 50 mg daily 75 mg daily 100 mg daily 200 mg daily * Titrated dose 50–100 mg 24 weeks FOLLOW-UP Optional extension 6 m + 6m f-up * Titration after 12 weeks based on E2 serum level at weeks 4 and 8 Target enrollment of 330 patients • ~70 sites in US (>50% of patients) • 15 sites in EU Recruitment completed November 2017


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OBE2109 reduced menstrual bleeding and uterine volume in uterine fibroids (no add back) KLH1202 TRIAL: % OF DAYS WITH BLEEDING DURING 12-WEEK    TREATMENT PERIOD KLH1202 TRIAL: TIME TO NO BLEEDING FOR UTERINE    FIBROIDS PATIENTS KLH1202 TRIAL: CHANGE IN UTERINE VOLUME OVER TIME 50.0 (%) 40.0 Bleeding 30.0 with 28.98 Days 24.18 of 20.0 13.63 * Percentage 10.0 7.99 0.0 Placebo OBE2109 50 mg OBE2109 100 mg OBE2109 200mg p < 0.01 * Two sample t-test (vs Placebo) 100 90 80 (%) 70 estimate 60 Meier 50 40 an -Kapl 30 20 10 0 0 28 56 84 112 Time (Days) OBE2109 50 mg OBE2109 100 mg OBE2109 200 mg Placebo Censor 100 Mean±SEM OBE2109 50 mg OBE2109 100 mg OBE2109 200 mg Placebo volume 50 uterine 0 in ** * ** *** *** ** ** Percentage *** -50 *** Δ *** p < 0.05 * p < 0.01 ** p < 0.001 *** vs Placebo -100 Pretreatment Week 1 Week 4 Week 8 Week 12 Post-treatment (Week 4) Time (Weeks)


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OBE2109 Phase 3 clinical trials (PRIMROSE) in uterine fibroid patients Primary endpoint: Responder-HMB Reduction 2H:19 28 weeks 24 weeks 8–14 weeks 16-OBE2109-008 100% US sites n = 100 n = 100 n = 100 n = 100 n = 100 16-OBE2109-009 70% Europe 30% US sites n = 100 n = 100 n = 100 n = 100 n = 100      24 weeksPlacebo + placebo add-back Placebo + placebo add-back200mg + add-back 100mg +placebo add-back100mg + placebo add-back 24w follow-up Screening100mg+add-back100 mg + add-back 200mg+placebo add-back200 mg + add-back 200mg+add-back200 mg + add-back Placebo + placebo add-back200mg + add-back 100mg +placebo add-back100mg + placebo add-back 24w follow-up Screening100mg+add-back100 mg + add-back 200mg+placebo add-back200 mg + add-back 200mg+add-back200 mg + add-back IND granted in April 2017 Currently recruiting • Aiming at supporting the registration of two regimens of administration


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OBE2109 potential Best in Class GnRH antagonist


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OBE2109 potential best in class based upon PK/PD profile     OBE2109 ELAGOLIX*RELUGOLIX* Half-Life14-15 hours2-6 hours37-42 hours Bioavailability> 80%30 – 50 %11% Active transport limitingNoInhibitor & Saturable substrate Substrate absorption (P-gP) Volume of distribution11 L>2,000 L>20,000 L (unadjusted for bioavailability) Partition into fatNoYesYes Food Effect NoYesYes CYP3A4 induction (possible NoYesNo adverse impact on ABT)


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OBE2109 potential best in class based upon dosing options     OBE2109 ELAGOLIX*RELUGOLIX* Moderate dose withoutABT Moderate dose without ABT (150mg)High dose with ABT (40mg) EndometriosisHigh dose with ABTHigh dose with ABT (200mg bid)same dose 3 months only w/o ABT Moderate dose without ABTHigh dose with ABT (40mg) Uterine FibroidsHigh dose with ABT(300mg bid) High dose with ABTsame dose 3 months only w/o ABT Treatment durationPlacebo control for 12 monthsPlacebo control for 6/12 monthsPlacebo control for 6 months


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ABT May Not be Appropriate for All Patients: Exogenous vs endogenous estrogens Add-back draw backs ✓Reduced bleeding control (spotting and/or breakthrough bleeding): > 50% ✓Study and post marketing side effects: breast pain (24%)1, mood, libido, water retention ✓Reduction in anti-fibroid efficacy: approximately 10% ✓Contra-indication (estrogen dependent neoplasia, history/risk of thrombo-embolic disease, liver dysfunction)1: 5 %     OBE2109 100 mg100 mg100 mg200 mg200 mg Daily Dose(n=14)(n=14)(n=15)(n=15)(n=15) Data fromAdd-Back E2/NETA-0.5mg/0.1mg1mg/0.5mg-1mg/0.5mg OBE2109 PK/PD study3Amenorrhea (no bleeding)86%21%53%87%33% Amenorrhea + (spotting only)93%57%93%100%60% Leuprolide Acetate (LA)discontinuation rate (within 6 months) in endometriosispatients2 ✓ LA alone:59.6%1 Activella US FDA label 2 Soliman A.M. et al., J Manag Care Spec Pharm 2016; 22 (5):573-87 ✓ LA + ABT:37.9%—40.2%3 Pohl O. et al., J Clin Endocrinol Metab 2018; 103(2): 497-504


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OBE2109 Profile Testing – US Gynecologists prefer a “low dose without ABT” as first line therapy • Product preference Qualitative Market Research Quintiles-IMS for ObsEva -October 2017. 30 US Gynecologists took part in this qualitative study.     Neutral scenario After showing OBE2109 PRODUCT 1:PRODUCT 2:PRODUCT 1:PRODUCT 2 (OBE2109): 1. High dose of oral1.High dose of oral GnRH 1. High dose of oral 1.OBE2109 oral tablet GnRH antagonistantagonist with GnRH antagonist with200mg given once per with mandatorymandatory add-back mandatory add-day, with mandatory add-back (as theORback (as the onlyadd-back only option)2.Low dose of oral GnRHoption)OR antagonist without add-2.OBE2109 oral tablet back75mg given once per day, without add-back [2 out of 30 respondents][28 out of 30 respondents][1 out of 30 respondents][29 out of 30 respondents] 7% respondents93% respondents3% respondents97% respondents preferred Product 1preferred Product 2preferred product 1preferred product 2 ReasonsReasons Reasons Reasons • No time to try different•More flexibility with• No time to try different•Dose flexibility dosages in severeaddback therapydosages in severe•Low dose so patientspatients considered to have •Convenient optionlesser side effects OBE2109 profile testing – Qualitative market research in the USA, October 2017 Base (N) = 30


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GnRH antagonist market takeaways 1 Large patient populations at 2.5 – 4+ million for each indication 2 Ample room for multiple market entrants 3 Patients not “one size fits all” – Availability of dosing options preferred by US Gynecologists OBE2109 potential Best in Class: 4 • Once-a-day, no adverse impact of food intake and no metabolic impact on ABT • Availability of two dosing options for both indications (ABT & No ABT) 5 Time to market: AbbVie leading and investing in early market development


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NOLASIBAN to Improve IVF Outcomes


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NOLASIBAN (OBE001): Oral oxytocin receptor antagonist to improve IVF outcomes NOLASIBAN AT-A-GLANCE Oxytocin Receptor Antagonist Licensed from Merck Serono IP Protection to 2035-2036 (COM 2027 with PTE) NOLASIBAN INDICATIONS In Vitro Fertilization (IVF) Market size: 2.1-2.4 million ART cycles/year globally in 2013* (230K in US in 2015, 800K in Europe in 2014 and 420K in Japan in 2015) ART cycle cost: $8-15K in the US, EUR 2-10K in the EU and $3-6k in Japan Estimated global sales of fertility drugs 2 bn USD** LANDSCAPE Atosiban (Tractocile®) approved ex-US for Preterm labor I.V. peptide No label for IVF use NOLASIBAN: Well-characterized profile, Phase 2 clinical trial completed, EU Phase 3 primary endpoint completed 650 subjects exposed Orally active—Well tolerated tmax at 2h; t1/2= 12h; High bioavailability Single oral 900mg optimal dose * Source: ICMART 2013 estimate; **IMS Health Incorporated estimate as of 2015.


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ART: Day 5 ET preferred option Fresh Embryo Transfer (Europe%) ET Day 3 US% 39% 19% ET Day 5 36% 38% rozen Embryo for FET 25% 43% 24


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Blocking the oxytocin receptor is a potential target for improving pregnancy & live birth rates in ART Comparative, randomized trials on the use of Atosiban (IV infusion) prior to ET in ART Meta-analysis * (Huang et al. 2017) Clinical Pregnancy Rate (6 studies; n = 1754) Atosiban 51.2% p < 0.001 Control 40.7% Live Birth Rate (3 studies; n = 1190 ) Atosiban 38.6% p < 0.083 Control    30.8% Oxytocin X Oxytocin Receptor Smooth Uterine Arteries Endometrium Muscle Lining Cells Uterine Endometrium Contractions Receptivity Uterine Blood Flow * No of embryos transfered: 1–4


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Nolasiban Phase 2 Efficacy Results As per protocol, all ET were performed on day 3 in the trial FULL ANALYSIS RESULTS      Nolasiban Nolasiban Nolasiban Nolasiban PLACEBOTREND TEST 100 mg300 mg900 mgAll doses Number of subjects65626060182 Clinical pregnancy rate at 33.8%46.8%35.0%46.7%42.9%p=0.33 6 weeks after ET day Ongoing pregnancy rate at 29.2%43.5%*35.0%45.0%*41.2%p=0.15 10 weeks after OPU day Live birth rate 29.2%40.3%35.0%43.3%39.6%p=0.20 (baby born alive ³ 24 weeks gestation) Relative change in uterine contractions0.0%-8.7%-4.0%-13.3%** *p£0.10 **p£0.05, Nolasiban vs Placebo


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IMPLANT2 A phase 3, double-blind, placebo-controlled study to assess the safety and efficacy of a single oral administration of nolasiban to improve pregnancy rates following IVF or ICSI in Day 3 and Day 5 Fresh Embryo Transfer cycles.


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NOLASIBAN Phase 3 clinical trial protocol (IMPLANT2) 41 fertility centers in 9 European countries Main Study Primary Analysis Follow-Up 10 week 1 month pregnancy rate Not preg. FU 900 mg, n=380 D3 or D5 SCREENING IVF/ICSI ET Placebo, n=380 7–8 months 6 months Preg.* Randomize Preg. FU Neonatal FU n=314 * Estimate Target enrollment of 760 patients • Trial conducted in Europe FPI March 2017 – Recruitment completed August 2017 –Top Line Results February 2018 28 Note: N=760 gives 90% power to show significant difference if the true effect size is 11-12%. It will still show a significant 27 effect if the observed size is about 6-7%.


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Results: Demographics and baseline characteristics      D3D5Pooled D3/D5 Nolasiban Nolasiban Nolasiban Mean (SD) UnitPlaceboPlacebo Placebo 900 mg900 mg900 mg Number ofn194194196194390388 subjects Ageyears31.4 (3.3)31.1 (3.2)31.3 (3.2)31.1 (3.3)31.4 (3.2)31.1 (3.3) BMIkg/m223.94 (4.12)24.11 (4.09)23.67 (4.46)23.80 (4.65)23.80 (4.29)23.95 (4.38) Oocytesn9.0 (4.6)8.6 (4.2)9.8 (4.1)10.9 (4.2)9.4 (4.4)9.7 (4.3) retrieved Good qualityn2.7 (2.2)2.5 (1.9)2.3 (1.6)2.7 (2.0)2.5 (2.0)2.6 (2.0) embryos P4 hCG day nmol/L 2.0 (1.3)1.8 (1.0)1.9 (1.0)1.9 (1.0)2.0 (1.2)1.9 (1.0) P4 ET daynmol/L 316 (233)295 (130)393 (189)409 (191)355 (215)352 (173)


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Results: Efficacy Primary endpoint: Pooled D3 and D5      Pooled D3and D5 Nolasiban PlaceboIncreasep 900 mg n390388 Ongoing pregnancyrateat28.5%35.6%7.1%0.031 10 weeks Absolute 7.1% increase compared to placebo Relative 25% increase compared to placebo


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Results: Efficacy Secondary endpoints: Individual D3 and D5      D3D5 Nolasiban Nolasiban PlaceboDeltapPlaceboDeltap 900 mg900 mg n194194196194 Ongoing pregnancy22.2%25.3%3.1%0.47734.7%45.9%11.2%0.034* rate at 10 weeks Clinical pregnancy rate* at 6 weeks22.7%27.3%4.6%0.29035.7%47.4%11.7%0.022 Positive pregnancy 33.5%35.6%2.1%0.66645.9%54.6%8.7%0.112 test at 14 days * Nolasiban increases the relative ongoing pregnancy rate by 32% following single embryo transfer at Day5


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Results: Safety Summary of Treatment Emergent AEs: no safety concern      ET D3ET D5Pooled D3 / D5 PlaceboNolasiban PlaceboNolasiban PlaceboNolasiban N=195N=193N=196N=194N=391N=387 Parameter SubjectsSubjects Subjects Subjects Subjects Subjects n(%)n(%)n(%)n(%)n(%)n(%) Any TEAE44 (23)34 (18)55 (28)51 (26)99(25)85(22) TEAE related to IMP02 (1)*02 (1)**04 (1) Serious TEAE2 (1)2 (1)7 (4)2 (1)9 (2)4 (1) Serious TEAE related to IMP000000 Fatal TEAE000000 Preliminary note:—Congenital malformation: Placebo: 1; Nolasiban: 1—Ectopic pregnancy: Placebo: 4; Nolasiban: 1 TEAE related to IMP (all mild): * Feeling hot; Urticaria    ** Dizziness; Headache


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Conclusions: Nolasiban has the potential to increase clinical pregnancy rate w/o increasing multiple pregnancy rate • Nolasiban significantly increased ongoing pregnancy rate at 10 weeks: Pooled D3/D5 (primary): Placebo 28.5%, Nolasiban 35.6%, p=0.03 (7.1% absolute increase, 25% relative increase). • The largest increase in ongoing pregnancy rate was seen with D5 ET, Placebo 34.7%, Nolasiban 45.9%, p=0.03 (11.2% absolute increase, 32% relative increase). • Nolasiban very well tolerated with a safety profile not different from placebo. • Potential of nolasiban primarily as an agent to increase IVF efficacy, but also to increase the safety of IVF by supporting SET, hence dramatically reducing multiple pregnancies (from 25 -40% to â‰^ 5%). • As Standard of Care increasingly moves to D5 ET, US IMPLANT3 trial will focus on D5 ET.


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OBE022 for Preterm Labor


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OBE022: Potential first-in-class, oral and selective PGF2α receptor antagonist for preterm labor (PTL) OBE022 AT-A-GLANCE • Prostaglandin F2α (FP) receptor antagonist • Licensed from Merck Serono • IP Protection through 2037 • (COM 2037 with PTE) OBE022 INDICATIONS • Preterm labor (GA 24-34week) • Incidence: USA: 500,000; EU: 500,000; Asia: 6,900,000* • Economic burden for premature infants: ~$26 billion in the U.S. ($16.9 billion in infant medical care) COMPETITION No drug approved for acute use in the US; atosiban used in the EU;    Progesterone indicated for prevention in a sub-population in the US Phase 1 & DDI clinical trials completed • Oral administration • Favorable preclinical study outcomes * WHO ‘Born Too Soon: The Global Action Report on Preterm Birth’ 2012)


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Blocking PGF2α receptor has potential to treat PTL with improved safety over NSAIDs Phospholipids ArachidonicAcid Indomethacin PGHS-1/2 = COX1/2 PGH2 PGE2 PGF2α EP1 EP2    FP EP3 EP4 UTERUS:    CONTRACT RELAX CONTRACT ‘Inflammation’    Prostaglandins    Cytokines Chemokines Phospholipids ArachidonicAcid PGHS-1/2 = COX1/2 PGH2 OBE022 PGE2 PGF2α EP1 EP2    FP EP3 EP4 UTERUS: CONTRACT RELAX CONTRACT kidney, brain, vascular smooth muscle Vasoconstriction of ductus arteriosus, renal and mesenteric arteries Platelet aggregation inhibition RUPTURE CONTRACT DILATE PGF2α contracts the myometrium and PGF2α metabolites rise in amniotic fluid before and during labor PGF2α upregulates enzymes causing cervix dilatation and membrane rupture


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PROLONG Ph2a Study (Parts A and B) Preliminary safety Final Part A Main study end End of Infant FU & PK analysis Main analysis Part A Dosing for 7d Maternal + neonatal FU 24-month Infant FU 8 patients Open-label: Atosiban + OBE022 Final Part B Main analysis Part B Dosing for 7d Maternal + neonatal FU 24-month Infant FU 60 patients + up to 60 patients Double-blind: Atosiban + OBE022 vs Atosiban + PLACEBO


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Thank You