Innovating Women s Reproductive Health and Pregnancy Therapeutics. J u l y 2017

Transcription

1 Innovating Women s Reproductive Health and Pregnancy Therapeutics J u l y 2017

2 Disclaimers 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, 2016, as filed with the Securities and Exchange Commission on April 21, 2017 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. Proprietary and Confidential Material 2

3 ObsEva is committed to the development and commercialization of novel therapeutics for serious conditions that compromise a woman s reproductive health and fertility Non-malignant gynecological disorders are one of the areas of women s health that has seen little progress over the last two decades due to fragmented care, lack of understanding of pathophysiology and research focus on diseases that impact mortality. Women s Health Research: Progress, Pitfalls and Promise Institute of Medicine Proprietary and Confidential Material 3

4 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 Preterm Labor Preeclampsia Age 50+ Menopause Menopause Symptoms Hormone Replacement Therapy Osteoporosis Generics / Innovation by Big Pharma Proprietary and Confidential Material * Source: IMS Health Incorporated estimate as of

5 Robust late-stage pipeline for women s reproductive health & pregnancy PRODUCT CANDIDATE PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NEXT MILESTONE COMMERCIAL RIGHTS OBE2109* Oral GnRH receptor antagonist Endometriosis Uterine Fibroids US/EU Phase 2b Data 1H 2018 US/EU Phases 3 Initiated Data 2019 Worldwide ex-asia NOLASIBAN Oral oxytocin receptor antagonist IVF EU Phase 3 Initiated Data 2Q 2018 Worldwide OBE022 Oral PGF 2α receptor antagonist Preterm Labor Phase 2a Data 2H 2018 Worldwide Proprietary and Confidential Material * Kissei Pharmaceutical developing for Asia 5

6 Unique mix of clinical and operational experience provides indepth 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 30+ with successful experience in world-wide development and commercialization of women health products ObsEva Proprietary and is Confidential listed Material on The NASDAQ Global Select Market and trades under the ticker symbol "OBSV" 6

7 ObsEva at-a-glance: a smarter, highly focused approach Best-in-class GnRH antagonist Compelling pipeline Sizable target indications with significant unmet need Multiple near-term data catalysts Highly experienced management team OBE2109: Potential best-in-class oral gonadotropin-releasing hormone (GnRH) receptor antagonist NOLASIBAN (OBE001): Potential to significantly improve clinical pregnancy and live birth rates after in vitro fertilization (IVF) OBE022: potential first-in-class therapy to suppress preterm labor and delay or avoid preterm birth Targeting indications with millions of underserved patients globally Multiple programs with significant potential OBE2109: Phase 2b endometriosis data in 1H18 NOLASIBAN: Phase 3 data in 2Q18 OBE022: Initiate Phase 2a proof-of-concept clinical trial in 2H2017 Management team has strong track record of successfully in-licensing, developing and commercializing treatments for women s reproductive health and pregnancy ObsEva is listed on The NASDAQ Global Select Market and trades under the ticker symbol "OBSV" Proprietary and Confidential Material 7

8 OBE2109 for Endometriosis and Uterine Fibroids 8

9 Unmet medical need in endometriosis & uterine fibroids therapy LARGE U.S. MARKET SIZE Uterine Fibroids: 4 MILLION WOMEN diagnosed and treated annually Endometriosis: 2.5 MILLION WOMEN diagnosed and treated annually Proprietary and Confidential Material OLDER, SUBOPTIMAL EXISTING TREATMENTS LUPRON INJECTIONS cause flares, worsening of symptoms, no titration possible, prolonged and variable reversibility time ORAL CONTRACEPTIVES and progestin, only partially effective, safety risks SURGICAL INTERVENTIONS costly and invasive

10 OBE2109: Potential best-in-class, oral, GnRH receptor antagonist with and without ABT OBE2109 AT-A-GLANCE GnRH Receptor Antagonist OBE2109 (KLH-2109) Licensed from Kissei (WW rights, excludes Asia) IP Protection* to 2036 (COM 2032) > 750 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 COMPETITION Standard of Care: Lupron, oral contraceptives, surgery Esmya approved in EU for uterine fibroids Elagolix (AbbVie/Neurocrine) in Phase 3 Development Relugolix (Myovant/Takeda) in Phase 3 Development Proprietary and Confidential Material * Including PTA/PTE (Patent Term Adjustment / Patent Term Extension) 10

11 GnRH agonists vs antagonists: Mechanism of action Initial overstimulation of GnRH receptors leads to an increase in LH and estradiol production Chronic administration eventually leads to suppression of LH, resulting in suppression of estradiol GnRH GnRH agonist Uterus GnRH agonist Estradiol Hypothalamus Anterior pituitary gland FSH, LH Ovary GnRH GnRH antagonist GnRH antagonist (blocker) Uterus Estradiol Hypothalamus Anterior pituitary gland FSH, LH Ovary GnRH antagonist have an immediate onset of action, preventing gonadotrophin release through receptor blockade, leading to rapid suppression of LH and estradiol Competitively prevent endogenous GnRH from binding and activating its pituitary receptor Induce neither downregulation nor desensitization of the receptors Reduction of serum E2 suppresses the growth and symptoms of estrogen-dependent tissues like endometriosis, endometrium and fibroids Proprietary and Confidential Material 11

12 Potential benefits of GnRH antagonists vs GnRH agonists (Lupron) 1 2 No initial flare with worsening of symptoms, rapid reversibility Oral dosing enhances patient compliance 3 4 Allows for partial estrogen suppression Two dosage options to better meet individual needs 5 More suitable for chronic therapy Proprietary and Confidential Material 12

13 Finding a balance between level of estradiol suppression, associated symptoms, and BMD protection Estradiol measured at 1-2 months after treatment initiation was shown to be a reliable predictor of 6-month BMD change. Estradiol between 20 and 60 pg/ml is considered range allowing treatment of endometrial pain while minimizing BMD effects. Optimal treatment approach is to target estradiol level that improves symptoms without significant bone impact, using ABT only as needed. High dose GnRH antagonist & addback Proprietary and Confidential Material Moderate dose GnRH antagonist & no add-back BMD: Bone mineral density ESSS: Endometriosis symptom severity score 1. Integrated Pharmacometrics and Systems Pharmacology Model-Based Analyses to Guide GnRH Receptor Modulator Development for Management of Endometriosis Riggs MM et al CPT: Pharmacometrics & Systems Pharmacology 1, e11. 13

14 OBE2109 Plasma Concentration (ng/ml) Relative Concentration of Luteinizing Hormone (% Baseline) OBE2109 consistent PK/PD profile with low variability, high bioavailability & low volume of distribution in Phase 1 PK/PD trial MEAN OBE2109 CONCENTRATION OVER TIME LH REDUCTION FROM BASELINE OVER TIME 1'000' '000 10'000 Mean±SEM OBE mg OBE mg OBE mg OBE mg OBE mg OBE mg Mean±SEM OBE mg OBE mg OBE mg OBE mg OBE mg OBE mg Placebo Half life = 15h: once a day dosing Low volume of distribution (Vd 11 L): No dose adjustment for weight 1' No food effect observed No significant differences between women of Japanese and European descent Time (hr) Time (hr) Proprietary and Confidential Material 14

15 OBE2109 PK/PD results in pre-menopausal women Table 1: Median (IQR: 25 75%) E2 level after week 1 and 6 of treatment OBE2109 Daily Dose 100 mg (n=14) 100 mg (n=14) 100 mg (n=15) 200 mg (n=14) 200 mg (n=15) Add-Back E2/NETA - 0.5mg/0.1mg 1mg/0.5mg - 1mg/0.5mg E2 Week 1 [pg/ml] 12 (9-18) 25 (18-30) 35 (26-45) 5 (4-7) 27 (22-38) E2 Week 6 [pg/ml] 18 (9-27) 40 (31-50) 34 (26-47) 3 (2-3) 25 (21-34) OBE2109 Daily Dose Table 2: Bleeding pattern during the last 4 weeks of treatment 100 mg (n=14) 100 mg (n=14) 100 mg (n=15) 200 mg (n=15) 200 mg (n=15) Confirmation of OBE2109 of 100mg/200mg efficacy in Caucasian women Optimal ABT E2/NETA 1mg/0.5mg Median E2 level in 100 mg group indicate ~50% of patients may be in target 20-60pg/mL range Add-Back E2/NETA - 0.5mg/0.1mg 1mg/0.5mg - 1mg/0.5mg Amenorrhea (no bleeding) Amenorrhea + spotting only 86% 21% 53% 87% 33% 93% 57% 93% 100% 60% Some drawback to ABT as measured by reduced bleeding control All regimens were welltolerated and no safety signal emerged Proprietary and Confidential Material 15

16 Percentage Δ Average Severity of Pelvic Pain Endometriosis: OBE2109 suppressed estradiol levels to target range & reduced pain severity across three Phase 2 clinical trials 100 KLH1202 TRIAL: % OF PATIENTS AT VARIOUS ESTRADIOL LEVELS IN KLH1202 TRIAL AT WEEK pg/ml 20 pg/ml and < 60 pg/ml < 20 pg/ml KLH1202 TRIAL: AVERAGE CHANGE IN SEVERITY OF PELVIC PAIN OVER TIME (MENSTRUAL AND NON- MENSTRUAL PAIN COMBINED) OBE mg OBE mg OBE mg Placebo Placebo OBE mg OBE mg OBE mg -1 *** *** *** *** ** Time (Weeks) ** *** ** * * p < 0.05* p < 0.01** p < 0.001*** Two sample t -test vs Placebo Pretreatment Week 4 Week 8 Week 12 Post-treatment (Week 4) Proprietary and Confidential Material 16

17 Percentage of Days with Bleeding (%) Kaplan-Meier estimate (%) Δ Percentage in uterine volume Uterine Fibroids: OBE2109 reduced menstrual bleeding & uterine volume 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 Mean±SEM OBE mg OBE mg OBE mg Placebo ** * ** * *** *** ** *** ** *** *** Placebo OBE mg OBE mg OBE mg Pretreatment Week 1 Week 4 Week 8 Week 12 Post-treatment Time (Days) (Week 4) p < 0.01 * Time (Weeks) Two sample t-test (vs Placebo) OBE mg OBE mg OBE mg Placebo Proprietary and Confidential Material Censor 17 p < 0.05 * p < 0.01 ** p < *** vs Placebo

18 GnRH antagonists in development have similar timelines in uterine fibroids, Elagolix leads in endometriosis UTERINE FIBROIDS Elagolix* Phase 3 Relugolix (1)* Phase 3 OBE2109 Phase 3 ENDOMETRIOSIS Elagolix* Phase 3 Regulatory Review Relugolix (1)* Phase 3 OBE2109 Phase 2b Phase 2b Primary Endpoint Results Proprietary and Confidential Material (1) Excludes development in Japan which is being conducted by Takeda. * Based on publicly available information and data for these other product candidates currently in development. 18

19 Dose options PK characteristics OBE2109 potential best in class: Optimal PK/PD & dual dosing options OBE2109 ELAGOLIX* RELUGOLIX* Half-Life hours 2-6 hours hours Bioavailability High Moderate to Low Low Active transport limiting absorption (PgP) No Yes- saturable Yes Volume of distribution 11 L >2,000 L >20,000 L Fat accumulation No Yes Yes +++ Food Effect No Yes Yes Overall PK/PD variability Low High Moderate? Endometriosis Dosing options Moderate dose without ABT High dose with ABT Moderate dose without ABT High dose with ABT High dose with ABT (same dose 3 months only w/o ABT) Uterine Fibroids Dosing options Moderate dose without ABT High dose with ABT High dose with ABT High dose with ABT ABT: Add Back Therapy Proprietary and Confidential Material 19 *Based on publicly available information and data for these other product candidates currently in development

20 ABT May Not be Suitable for All Patients: Exogenous vs endogenous estrogens Add-back draw backs: Contra-indication (estrogen dependant neoplasia, history/risk of thrombo-embolic disease, liver dysfunction) 1 : 5 % Reduction in efficacy: approximately 10% Reduced bleeding control (spotting and/or breakthrough bleeding): > 50% Side effects: e.g. breast pain (20%) 1 Leuprolide Acetate (LA) discontinuation rate (within 6 months) in endometriosis patients 2 LA alone: 59.6% LA + ABT: 37.9% % OBE2109 is the only GnRH antagonist being developed With and without ABT for both endometriosis and fibroids At two different dosage levels allowing for both partial and full E2 suppression 1 Activella US FDA label 2 Soliman A.M. et al., J Manag Care Spec Pharm 2016; 22 (5): Proprietary and Confidential Material 20

21 OBE2109 Phase 2b clinical trial (EDELWEISS) in patients with endometriosis 12 weeks Placebo Primary endpoint: pain scores 12 weeks 8 14 weeks 50 mg daily 50 mg daily Key secondary endpoint: BMD 24 weeks LEAD-IN 75 mg daily 75 mg daily FOLLOW-UP 100 mg daily 100 mg daily 200 mg daily 200 mg daily 75 mg daily* * Titrated dose mg Optional extension 6 m + 6m f-up * Titration after 12 weeks based on E2 serum level at weeks 4 and 8 Currently recruiting Target enrollment of 330 patients ~70 sites in US (up to 75% of patients) 15 sites in EU (Ru, Ukr, Pl) Pre-IND meeting completed in March 2016 to discuss the trial design IND granted in June 2016 Proprietary and Confidential Material 21

22 OBE2109 Phase 3 clinical trials (PRIMROSE) in patients with uterine fibroids began April OBE % US sites n = weeks 24 weeks Placebo + placebo add-back Primary endpoint: Reduction of HMB 28 weeks Placebo + placebo add-back 200mg + add-back 24 weeks n = 100 n = 100 Screening 100mg + placebo add-back 100 mg + add-back 100mg + placebo add-back 100 mg + add-back 24w follow-up n = mg + placebo add-back 200 mg + add-back n = mg + add-back 200 mg + add-back 16-OBE % Europe 30% US sites n = 100 Placebo + placebo add-back 200mg + add-back n = 100 n = 100 Screening 100mg + placebo add-back 100 mg + add-back 100mg + placebo add-back 100 mg + add-back 24w follow-up n = mg + placebo add-back 200 mg + add-back n = mg + add-back 200 mg + add-back Currently recruiting Aiming at supporting the registration of two regimens of administration Proprietary and Confidential Material 22

23 GnRH antagonist market takeaways 1 2 Large patient populations at million for each indication Ample room for multiple market entrants Patients not one size fits all Large companies (AbbVie and Allergan) investing in early market development Targeted Salesforce of projected to cover ~30,000 OB/GYNs Proprietary and Confidential Material

24 NOLASIBAN to Improve IVF Outcomes 24

25 NOLASIBAN (OBE001): Oral oxytocin receptor antagonist to improve IVF outcomes NOLASIBAN AT-A-GLANCE Oxytocin Receptor Antagonist Licensed from Merck Serono IP Protection to (COM 2027 with PTE) NOLASIBAN INDICATIONS In Vitro Fertilization (IVF) Market size: 1.6 M ART/IVF cycles/year globally (~210K in US in 2014, ~620K in Europe in 2012 and ~325K in Japan in 2012) 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* COMPETITION Atosiban (Tractocile ) marketed ex-us (IV only) Barusiban Ph2 SC injection twice/day Well-characterized profile, Phase 2 clinical trial completed >240 subjects Orally active - tmax at 2h; Single oral dose of 900 mg OBE001 observed to exposed Well tolerated t1/2= 12h; High increase the live birth rate up to 51% compared to 31% bioavailability in the placebo group Proprietary and Confidential Material 25 * Source: IMS Health Incorporated estimate as of 2015.

26 ART procedures and options for embryo transfer (ET) Fresh Embryo Transfer ET Day 3 ET Day 5 50% Medical need for assisted reproductive technology 11% of couples present with infertility IVF process has an overall live birth rate between ~21% and 33% NOLASIBAN (OBE001) has the potential to be the first-in-class orally available oxytocin antagonist 25% Frozen Embryo for FET 25% Proprietary and Confidential Material 26

27 Oxytocin receptor is a validated target for improving pregnancy & live birth rates in ART Oxytocin X Oxytocin Receptor Comparative, randomized trials on the use of Atosiban prior to ET in ART Smooth Muscle Cells Uterine Arteries Endometrium Lining Meta-analysis of 6 studies* (Huang et al. 2017) n = 1754 Uterine Contractions Uterine Blood Flow Endometrium Receptivity Atosiban CPR 51.2% Control CPR 40.7% p < Increase Clinical Pregnancy and Live Birth Rates * No of embryos transfered: 1 4 Proprietary and Confidential Material 27

28 Nolasiban Phase 2 Efficacy Results FULL ANALYSIS RESULTS Absence of Dose Response PLACEBO Nolasiban 100 mg Nolasiban 300 mg Nolasiban 900 mg Nolasiban All doses TREND TEST Number of subjects Clinical pregnancy rate at 6 weeks after ET day Ongoing pregnancy rate at 10 weeks after OPU day Live birth rate (baby born alive 24 weeks gestation) 33.8% 46.8% 35.0% 46.7% 42.9% p= % 43.5%* 35.0% 45.0%* 41.2% p= % 40.3% 35.0% 43.3% 39.6% p=0.20 Relative change in uterine contractions 0.0% -8.7% -4.0% -13.3%** *p 0.10 **p 0.05, Nolasiban vs Placebo Proprietary and Confidential Material 28

29 Pregnancy or live birth rate Nolasiban Phase 2 results: Relationship of pregnancy outcome to baseline E2, P4 & number of embryos transferred Logistic regression model: Clinical pregnancy vs E2, P4 and No. embryos transferred E2 P4 2 vs 1 embryos N Adj odds ratio % 40% 30% 20% 90% CI p-value Significant negative relationship between serum P4 on day of ET and clinical pregnancy 10% 0% n=60 n=62 n=61 n=62 Pre-dose P4 quartile 1 Pre-dose P4 quartile 2 Pre-dose P4 quartile 3 Pre-dose P4 quartile 4 Proprietary and Confidential Material 29

30 Pregnancy and live birth rate Nolasiban Phase 2 results: Efficacy (post-hoc analysis) 60% 50% 40% 30% 20% 10% On-going pregnancy rate (10 weeks) (Trend test: p=0.035) Live birth rate (Trend test: p=0.025) 0% N = 49 N = 50 N = 35 N = mg 300 mg 900 mg Placebo Nolasiban Nolasiban Nolasiban Excluding subjects in progesterone 4 th quartile at baseline Proprietary and Confidential Material 30

31 NOLASIBAN Phase 3 clinical trial (IMPLANT2): Recruitment of patients in process Main Study Primary Analysis Follow-Up 10 weeks 10 weeks 900 mg, n=380 Not preg. 1 month FU SCREENING D3 or D5 ET Placebo, n= months 6 months Preg.* Randomize Preg. FU Neonatal FU n=314 * Estimate Currently recruiting Target enrollment of 760 patients Trial being conducted in Europe First patients randomized in March 2017 Proprietary and Confidential Material Note: N=760 gives 90% power to show significant difference if the true effect size is 11-12%. It will still show a significant 31 effect if the observed size is about 6-7%.

32 OBE022 for Preterm Labor 32

33 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 week) 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 the US Phase 1 & DDI clinical trials completed Oral administration Favorable preclinical study outcomes Proprietary and Confidential Material * WHO Born Too Soon: The Global Action Report on Preterm Birth 2012) 33

34 Antagonism of PGF2α receptor has potential to treat PTL with improved safety over NSAIDs Phospholipids Arachidonic Acid Indomethacin PGHS-1/2 = COX1/2 PGH2 Inflammation Prostaglandins Cytokines Chemokines Phospholipids Arachidonic Acid PGHS-1/2 = COX1/2 PGH2 OBE022 PGE2 PGF2α PGE2 PGF2α EP1 EP3 EP2 EP4 FP EP1 EP3 EP2 EP4 FP UTERUS: CONTRACT RELAX CONTRACT UTERUS: CONTRACT RELAX CONTRACT kidney, brain, vascular smooth muscle Vasoconstriction of ductus arteriosus, renal and mesenteric arteries 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 Proprietary and Confidential Material 34

35 OBE022 inhibits uterine contractions synergy with SOC OBE022 INHIBITION OF SPONTANEOUS CONTRACTIONS IN PREGNANT RATS OBE022 EXERTED A SYNERGISTIC EFFECT IN COMBINATION WITH CALCIUM CHANNEL BLOCKER, NIFEDIPINE IN PRECLINICAL STUDIES OBE022 OBE002 Proprietary and Confidential Material * p<0.05; ** p<0.01; *** p<

36 Pretest - Treatment [Δ%] OBE022 did not induce vasoconstriction, no adverse impact on the neonatal renal function in contrast to indomethacin 150% 100% URINARY FLOW RATE p = 0.02 p = 0.02 Treatment with OBE022 did not result in any significant differences compared to vehicle Urinary Flow Rate IND: -50% OBE: 24% PEG: 54% 50% Renal vascular resistance IND: 40% OBE: -20% PEG: -37% 0% Glomerular filtration rate IND: -51% OBE: -13% PEG: 47% -50% Renal blood flow IND: -45% OBE: 34% PEG: 71% -100% Indomethacin OBE022 PEG400 Proprietary and Confidential Material 36

37 Phase 1/DDI results for OBE022 PHASE 1 SAD MAD Healthy women volunteers, single and multiple doses over 7 days Favorable safety profile and well-tolerated up to 1,300 mg single and 1,100 mg daily for 7 days (highest tested doses) PHASE 1 DRUG INTERACTIONS WITH BETAMETHASONE AND MgSO 4 SOC TO IMPROVE NEONATE OUTCOME DURING PRETERM LABOR No interactions PHASE 1 DRUG-DRUG INTERACTIONS WITH ATOSIBAN, NIFEDIPINE, i.e. tocolytics No clinically significant interaction with Atosiban Nifedipine exposure increased by co-administration with OBE022 NEXT STEPS Designing Phase 2a study in women with PTL, initiate in 2H 2017 Proprietary and Confidential Material 37

38 Recent accomplishments and expected catalysts Catalyst Expected Timing OBE022 (Preterm labor): Phase 1 DDI 2Q 2017 OBE2109: Phase 1 PK/PD add-back study data 2Q 2017 OBE2109 (Uterine fibroids): Initiation of two US/EU Phase 3 clinical trials 1H 2017 NOLASIBAN (IVF): Initiate European Phase 3 1H 2017 OBE022 (Preterm labor): Initiate Phase 2a proof-of-concept clinical trial 2H 2017 OBE2109 (Endometriosis): US/EU Phase 2b data 1H 2018 NOLASIBAN (IVF): EU Phase 3 data 2Q 2018 OBE022 (Preterm labor): US/EU Phase 2 data 2H 2018 OBE2109 (Uterine fibroids): US/EU Phase 3 data 2019/2020 Proprietary and Confidential Material 38

39 Thank You