|OBSEVA SA filed this Form 6-K on 03/30/2018|
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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such registration statements) and to be a part thereof from the date on which this report is filed, to the extent not superseded by documents or reports subsequently filed or furnished.
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.
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.
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 15Age 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
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
Robust late-stage pipeline for womens reproductive health & pregnancy PRODUCT CANDIDATE OBE2109* Oral GnRH receptor antagonist NOLASIBAN Oral oxytocin receptor antagonist OBE022 Oral PGF2Î± 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
2017 Accomplishments and 2018-19 Expected Milestones Milestone Timing OBE2109 (Endometriosis): Completed EDELWEISS trial EU/US patient enrollment4Q2017ï¼ NOLASIBAN (IVF): Completed IMPLANT2 trial recruitment 3Q2017ï¼ OBE022 (Preterm labor): Initiate Phase 2a PROLONG proof-of-concept clinical trial 4Q2017ï¼ NOLASIBAN (IVF): IMPLANT2 Phase 3 primary endpoint data 1Q2018ï¼ 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
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
OBE2109 for Endometriosis and Uterine Fibroids
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)
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
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.
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** Î *** p < 0.001*** Two sample t -test ** vs Placebo -1 Pretreatment Week 4 Week 8 Week 12 Post-treatment Time (Weeks) (Week 4)
OBE2109 Phase 2b clinical trial (EDELWEISS) in endometriosis patients Primary endpoint: VRS pain score responder rate 814 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 50100 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
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 *** Î *** 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)
OBE2109 Phase 3 clinical trials (PRIMROSE) in uterine fibroid patients Primary endpoint: Responder-HMB Reduction 2H:19 28 weeks 24 weeks 814 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
OBE2109 potential Best in Class GnRH antagonist
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)
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
ABT May Not be Appropriate for All Patients: Exogenous vs endogenous estrogens Add-back draw backs âReduced bleeding control (spotting and/or breakthrough bleeding): > 50% âStudy and post marketing side effects: breast pain (24%)1, mood, libido, water retention âReduction in anti-fibroid efficacy: approximately 10% âContra-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 â 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 â LA + ABT:37.9%40.2%3 Pohl O. et al., J Clin Endocrinol Metab 2018; 103(2): 497-504
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 differentMore flexibility with No time to try differentDose flexibility dosages in severeaddback therapydosages in severeLow dose so patientspatients considered to have Convenient optionlesser side effects OBE2109 profile testing Qualitative market research in the USA, October 2017 Base (N) = 30
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
NOLASIBAN to Improve IVF Outcomes
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 activeWell 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.
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
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: 14
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
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.
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 78 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%.
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)
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
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
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: 1Ectopic pregnancy: Placebo: 4; Nolasiban: 1 TEAE related to IMP (all mild): * Feeling hot; Urticaria ** Dizziness; Headache
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.
OBE022 for Preterm Labor
OBE022: Potential first-in-class, oral and selective PGF2Î± receptor antagonist for preterm labor (PTL) OBE022 AT-A-GLANCE Prostaglandin F2Î± (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)
Blocking PGF2Î± receptor has potential to treat PTL with improved safety over NSAIDs Phospholipids ArachidonicAcid Indomethacin PGHS-1/2 = COX1/2 PGH2 PGE2 PGF2Î± EP1 EP2 FP EP3 EP4 UTERUS: CONTRACT RELAX CONTRACT Inflammation Prostaglandins Cytokines Chemokines Phospholipids ArachidonicAcid PGHS-1/2 = COX1/2 PGH2 OBE022 PGE2 PGF2Î± 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 PGF2Î± contracts the myometrium and PGF2Î± metabolites rise in amniotic fluid before and during labor PGF2Î± upregulates enzymes causing cervix dilatation and membrane rupture
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