J u l y 1 7 , 2 0 1 9
Innovating Women’s Reproductive
Health and Pregnancy Therapeutics
KOL DISCUSSION:
IVF, EMBRYO
TRANSFER, AND
NOLASIBAN
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DISCLAIMER
Matters discussed in this presentation may constitute forward-looking statements. The forward-looking statements contained in thispresentation 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 significantlyfrom those expressed or implied in any forward-looking statement. Although we believe that the expectations reflected in theforward-looking statements are reasonable, we cannot guarantee future events, results, performance, or achievements. Some ofthe key factors that could cause actual results to differ from our expectations include our plans to develop and potentiallycommercialize our product candidates; our planned clinical trials and preclinical studies for our product candidates; the timing ofand our ability to obtain and maintain regulatory approvals for our product candidates; the extent of clinical trials potentially requiredfor our product candidates; the clinical utility and market acceptance of our product candidates; our commercialization, marketingand manufacturing capabilities and strategy; our intellectual property position; and our ability to identify and in-license additionalproduct candidates. For further information regarding these risks, uncertainties and other factors that could cause our actual resultsto differ from our expectations, you should read our Annual Report on Form 20-F for the year ended December 31, 2018, as filedwith the Securities and Exchange Commission on March 5, 2019 and our other filings we make with the Securities and ExchangeCommission from time to time. We expressly disclaim any obligation to update or revise the information herein, including theforward-looking statements, except as required by law. Please also note that this presentation does not constitute an offer to sell ora 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 theU.S. Food and Drug Administration. It is currently limited by federal law to investigational use, and no representation is made as toits safety or effectiveness for the purposes for which it is being investigated. The trademarks included herein are the property of theowners 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 sizeand growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautionednot to give undue weight to such estimates. In addition, projections, assumptions and estimates of our future performance and thefuture performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.
2
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TODAY’S AGENDA
Welcome and Introductions 9:00 - 9:05 Tim Adams
Overview of IMPLANT Trial results and progress 9:05 - 9:20 Ernest Loumaye
Nolasiban Market Assessment 9:20 - 9:35 Wim Souverijns
Discussion topics/questions
• Current trends in IVF
• Costs of failure
• Improving success rates
• Day 5 SET
• SET vs. DET implications
• Nolasiban potential
9:35 - 9:45
9:45 - 9:55
9:55 - 10:05
10:05 - 10:15
10:15 - 10:25
10:25 - 10:35
Dr. Pauli, Dr. Schnell, Dr. Sharara
Moderator:
Jean-Pierre Gotteland
Final Audience Q&A 10:35 - 10:55
3
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PANEL OF KEY OPINION LEADERS
4
Samuel Pauli, M.D.
Boston IVF
Lexington, MA
Surgical Director at Boston IVF
Member of Ohana Biosciences Clinical Advisory Board - Massachusetts
Vicki Schnell, M.D., FACOG
Center of Reproductive Medicine
Houston, TX
Fellow of the American Congress of Obstetricians and Gynecologists
Founder and Medical Director for the Center of Reproductive Medicine - Texas
Fady I. Sharara, M.D., FACOG
Virginia Center of RM
Reston, VA
Medical Director and Founder of VCRM
Clinical Professor at George Washington University – Washington, D.C.
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J u l y 1 7 , 2 0 1 9
Innovating Women’s Reproductive Health and Pregnancy Therapeutics
NOLASIBAN FOR
IMPROVING
LIVE BIRTH RATE
FOLLOWING BLASTOCYST
TRANSFER
5
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UTERINE CONTRACTIONS AT THE T IME OF EMBRYO
TRANSFER AFFECT PREGNANCY RATES AFTER IVFFA N C H I N E T A L . H U M A N R E P R O D . 1 9 9 8
Uterine contractions assessed by transvaginal ultrasound
Figure 1. Computerized assessment of uterine contraction (UC) frequency. After
determining the uterine section to be analysed (left panel), time-dependent changes
in endo–myometrial interfaces corresponding to UC were assessed (right panel).
6
Stepwise decrease in clinical pregnancy rates from the lowest to the highest
uterine contraction (UC) frequency groups (P, 0.001: ANOVA).
60%
40%
20%
0%
UC/min
≤3.0 3.1 – 4.0 4.1 – 5.0 >5.0
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OXYTOCIN ANTAGONISM FOR IVF: 1 ST CASE REPORT
7
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OXYTOCIN RECEPTOR ANTAGONIST GIVEN AT THE T IME
OF EMBRYO TRANSFERM E TA - A N A LY S I S ( H U A N G E T A L . P L O S O N E 2 0 1 7 )
8
Forest plot for clinical pregnancy rate in women undergoing in vitro fertilization
Control Atosiban
Clinical Pregnancy Rate (6 studies; n = 1754) 40.7% 51.2%
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OXYTOCIN ANTAGONISMMECHANISM OF ACTION: HYPOTHESIS
9
Functional Oxytocin receptors expressed
on human non pregnant uterus:
• Myometrium smooth muscle cells
• Uterus arteries smooth muscle cells
• Endometrium glandular epithelial cells
Oxytocin receptor antagonists :
• Reduce myometrium contractions1
• Enhance uterus blood flow2
• May enhance endometrium receptivity3
1ObsEva data on file; 2Kalmantis et al. 2012; 3Pierzinsky et al., 2019
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NOLASIBANFIRST, ORALLY ACTIVE, OXYTOCIN ANTAGONIST
10
Parameter Nolasiban
hKi Oxytocin Receptor (OTR) 48 nM
hKi Vasopressin 1a Receptor (V1a) 120 nM
Selectivity 2.5-fold OTR selective
Dose form and regimen Single oral administration 4 h prior ET
Tmax 1–4 h
Half-life 12 h
Duration of exposure ~ 48 h
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Trial Phase Treatments Purpose Status
IMPLANT 1Phase 2
EU
100, 300, 900 mg
placebo
Proof of concept and dose ranging in
D3 SET and DETCompleted
IMPLANT 2Phase 3
EU
900 mg
placeboConfirmatory trial in D3 and D5 SET Completed
IMPLANT 4Phase 3
EU
900 mg
placeboConfirmatory trial in D5 SET On going
IMPLANT 3Phase 3
US
900 mg
placeboConfirmatory trial in D5 SET In planning
NOLASIBAN COMPLETED CLINICAL TRIALSP H A S E 2 : 9 0 0 M G S E L E C T E D F O R F U R T H E R D E V E L O P M E N T
P H A S E 3 : P R I M A RY A N D S E C O N D A RY E N D P O I N T S M E T
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• Age 18–36 y
• Fresh D3 or D5 SET
• Max 1 failed previous IVF
• P4 ≤ 4.7 nmol on day hCG
• Vaginal P4 for luteal support
NOLASIBAN: PHASE 3 TRIAL IN IVFIMPLANT 2
Main study Follow Up
D3 ET
D5 ET
900mg nolasiban
n=194
900mg nolasiban
n=194
Placebo
n=194
Placebo
n=196
Not pregnant
Pregnant W6 W10Infant
FU
Randomize
2 weeks Primary Analysis
Ongoing
pregnancy
10 weeks
28 days 6 months
Birth
Screening
– IVF
9 weeks
Neonatal
FU
778 Patients enrolled – Trial conducted in 41 fertility centers in 9 European countries
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BASELINE CHARACTERISTICS (1/2)
13
Characteristicmean ± SD unless indicated otherwise
Pooled D3/D5 D3 ET D5 ET
Placebo
N=390
Nolasiban
N=388
Placebo
N=194
Nolasiban
N=194
Placebo
N=196
Nolasiban
N=194
Age — years 31.4 ± 3.2 31.1 ± 3.3 31.4 ± 3.3 31.1 ± 3.2 31.3 ± 3.2 31.1 ± 3.3
Body-mass index – kg.m-2 23.8 ± 4.3 24.0 ± 4.4 23.9 ± 4.1 24.1 ± 4.1 23.7 ± 4.5 23.8 ± 4.7
Primary Infertility – no. (%) 263 (67.4) 267 (68.8) 137 (70.6) 136 (70.1) 126 (64.3) 131 (67.5)
Type of infertility – no. (%)
Male factor only 122 (31.3) 131 (33.8) 62 (32.0) 70 (36.1) 60 (30.6) 61 (31.4)
Tubal factor 73 (40.1) 78 (46.7) 48 (50.5) 39 (44.3) 25 (28.7) 39 (49.4)
Ovulation dysfunction 53 (29.1) 42 (25.1) 20 (21.1) 21 (23.9) 33 (37.9) 21 (26.6)
Endometriosis 35 (19.2) 40 (24.0) 17 (17.9) 20 (22.7) 18 (20.7) 20 (25.3)
Menstrual irregularity 26 (14.3) 22 (13.2) 11 (11.6) 11 (12.5) 15 (17.2) 11 (13.9)
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BASELINE CHARACTERISTICS (2/2)
14
Characteristic mean ± SD
Pooled D3/D5 D3 ET D5 ET
Placebo
N=390
Nolasiban
N=388
Placebo
N=194
Nolasiban
N=194
Placebo
N=196
Nolasiban
N=194
Duration of stimulation – days 9.4 ± 1.8 9.4 ± 1.8 9.5 ± 1.8 9.7 ± 1.9 9.3 ± 1.8 9.2 ± 1.7
Gonadotrophin total dose – IU 1846 ± 645 1870 ± 650 1824 ± 722 1891 ± 727 1868 ± 561 1849 ± 563
Fertilization method – no. (%)
IVF 35 (9.0) 44 (11.3) 16 (8.2) 25 (12.9) 19 (9.7) 19 (9.8)
ICSI 355 (91.0) 344 (88.7) 178 (92) 169 (87.1) 177 (90.3) 175 (90.2)
Serum E2 on day of hCG – nmol/L 6653 ± 4283 7383 ± 4205 6400 ± 4726 6564 ± 3401 6906 ± 3553 8201 ± 4749
Serum P4 on day of hCG – nmol/L 1.97 ± 1.15 1.88 ± 0.99 2.01 ± 1.26 1.82 ± 0.99 1.93 ± 1.03 1.94 ± 0.98
No. of oocytes retrieved – no. 9.4 ± 4.4 9.7 ± 4.3 9.0 ± 4.6 8.6 ± 4.2 9.8 ± 4.1 10.9 ± 4.2
No. good quality embryos* – no. 2.5 ± 2.0 2.6 ± 2.0 2.7 ± 2.2 2.5 ± 1.9 2.3 ± 1.6 2.7 ± 2.0
* Good quality embryos defined according to Istanbul conference 2010 (D3) and Gardner grading scale (D5)
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7.1% absolute
increase or 25% relative increase in
LBR versus placebo
for pooled D3 and
D5 SET data
50%
40%
30%
20%
10%
0
Ongoing pregnancy
rate at 10 weeks (%)
Live birth rate (%)
p=0.031
28.5%
35.6%
p=0.025
27.7%
34.8%Placebo n=390
Nolasiban 900mg, n=388
15
EFFICACY RESULTS: PRIMARY ANALYSIS
POOLED D3/D5
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D3 SET D5 SET
50%
40%
30%
20%
10%
0Ongoing pregnancy
rate at 10 weeks (%)
Live birth rate (%)
p=0.034
34.7%
45.9%
p=0.025
33.2%
44.8%
Placebo n=194 Nolasiban n=194
50%
40%
30%
20%
10%
0Ongoing pregnancy
rate at 10 weeks (%)
Live birth rate (%)
22.7%24.7%
22.2%
25.3%
p=0.477 p=0.552
Placebo n=196 Nolasiban n=194
16
EFFICACY RESULTS FOR D5 ET: 35% RELATIVE INCREASE
IN LBR FOR NOLASIBAN VS. PLACEBO
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MATERNAL OUTCOMES A D V E R S E E V E N T S : N O L A S I B A N N O T D I F F E R E N T F R O M P L A C E B O
17
Spontaneously reported adverse
events up to week 10 post-ET
≥1% in any group
Placebo
N=391
Nolasiban
900 mg
N=387
Difference
(95% CI)
Abortion – no. (%) 44 (11.3) 38 (9.8) -1.4 (-8.4, 5.6)
Headache – no. (%) 11 (2.8) 11 (2.8) 0.0 (-7.0, 7.1)
Vaginal hemorrhage – no. (%) 11 (2.8) 8 (2.1) -0.8 (-7.8, 6.4)
Nausea – no. (%) 3 (0.8) 6 (1.6) 0.8 (-6.3, 7.9)
OHSS – no. (%) 4 (1.0) 4 (1.0) 0.0 (-7.1, 7.1)
Ectopic pregnancy – no. (%) 4 (1.0) 1 (0.3) -0.8 (-7.9, 6.3)
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NEONATAL OUTCOMES AT DELIVERY
18
Outcomemean ± SD unless indicated otherwise
Placebo
N=109
Nolasiban
900 mg
N=136
Difference
(95% CI)
Male – no. (%) 49 (45.0) 67 (49.3) 4.3 (-8.4, 16.8)
Female – no. (%) 60 (55.0) 69 (50.7) -4.3 (-16.8, 8.4)
Gestational age – weeks 38.7 ± 1.9 38.2 ± 2.8 -0.55 (-1.18, 0.07)
Weight – g 3174 ± 517 3137 ± 690 -37 (-194, 120)
Height – cm 50.9 ± 3.7 50.4 ± 4.6 -0.4 (-1.5, 0.6)
Head circumference – cm 34.3 ± 1.6 33.7 ± 2.2 -0.6 (-1.1, -0.04)
Apgar score 1 min 9.09 ± 1.28 9.01 ± 1.50 -0.08 (-0.44, 0.28)
Apgar score 5 min 9.65 ± 0.76 9.61 ± 0.84 -0.04 (-0.25, 0.17)
Congenital anomaly – no. (%) 4 (3.7) 5 (3.7) 0.0 (-12.6, 12.6)
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INFANT FOLLOW-UP ASQ-3 AT 6 MONTHSB O X P L O T F O R A G E S A N D S TA G E S Q U E S T I O N N A I R E ( A S Q - 3 )
TO TA L S C O R E S F O R P O O L E D D 3 / D 5
19
• Box – 25th to 75th percentiles
• Horizontal line – median
• Diamond – mean
• Whiskers – 1.5 times the interquartile
range above the 75th percentile and
below the 25th percentile.
N=99 N=124
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IMPLANT 2: CONCLUSIONS
• Nolasiban significantly increased live birth rate (LBR)
• The largest increase in LBR was seen with D5 SET
• Maternal, neonatal and infant outcomes were similar
between the nolasiban and placebo groups
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NOLASIBAN CLINICAL DEVELOPMENT PROGRAMO N G O I N G A N D P L A N N E D P H A S E 3 T R I A L S
21
Trial Phase Treatments Purpose Status
IMPLANT 1Phase 2
EU
100, 300, 900 mg
placebo
Proof of concept and dose ranging in D3
SET and DETCompleted
IMPLANT 2Phase 3
EU
900 mg
placeboConfirmatory trial in D3 and D5 SET Completed
IMPLANT 4Phase 3
EU
900 mg
placeboConfirmatory trial in D5 SET Ongoing
IMPLANT 3Phase 3
US
900 mg
placeboConfirmatory trial in D5 SET Planned
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Sample Size
Total (per arm)Endpoint
Study
PowerPlacebo Active
820 (410) Ongoing pregnancy 34.7% 45.9% 90%
IMPLANT 4 EU STUDY DESIGNREADOUT 4Q:19
Main study Follow Up
Screening D5 Set
900mg
n = 410
Placebo
n = 410
Not Pregnant
Pregnant W6 W10Preg.
FU
Infant
FU
2 weeks
Randomize
10 week
pregnancy rate
28 days 6 & 12
months
9 weeks
Primary analysis
22
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IMPLANT4 Trial initiated Q4:18 – MAA filing 4Q:19
800 patients, 40 centers in Europe, Russia, Canada
Day 5, Fresh SET
Primary endpoint 10 week ongoing pregnancy
Planning U.S. Ph3 program start
EOP2 FDA meeting completed Q2:19
Finalizing protocol and updating IND, trial start Q4:19/Q1:20
Getting started in China
Opening IND
Assessing development and commercial strategic options
2019 NOLASIBAN DEVELOPMENT PLAN
23
1 7 J u l y 2 0 1 9
N A S D A Q : O B S V | S I X : O B S N
Innovating Women’s Reproductive Health and Pregnancy Therapeutics
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INFERTILITY AND IVF MARKET SIZE,
NOT LIKE TRADITIONAL PHARMA
1 9% of 20-44 years of age (ESHRE 2018 ART Fact Sheet), 20-40 years of age (World Databank 2017)2 A TFR below 2.1 indicates a declining population
Women (20-44 year) with
Infertility1 7.2M 22.7M 4.8M 36.3M
ART Cycles/Year >800k >800k >260k >2.2M
Total Fertility Rate (TFR) 1.6 1.5 1.8 < 2.12
Fertility Drugs Sales (2017) $0.7B $0.3B(16% CAGR)
$1.2B $2.7B(10% CAGR)
Major
Markets
1 2 3
25
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NOLASIBAN – WHY GOING IT ON OUR OWN
Breakthrough clinical data
No competition anticipated
No change to standard of care
1
2
3
Strong value proposition4
12% absolute (35% relative) increase in LBR1 with no
observed safety or tolerability issues in IMPLANT 2
Simple & convenient addition to current practice
Nothing approved, nor in development
Increased productivity & similar LBR with single embryo
transfer while avoiding health & cost risks of multiple
pregnancies from multiple embryo transfer
Concentrated market5Modest commercial infrastructure to drive blockbuster
opportunity in US and EU
1 A 3-5% absolute increase considered clinically significant, Capri Group report, Human Reproduction, 2018
26
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A LEAN OPERATION TO COMMERCIALIZE
NOLASIBAN EFFECTIVELY
Highly concentrated
No competition
Sophisticated B2B market
1
2
3
100 FTEs can drive a blockbuster business
105 134 354 231 82 ~ 500ART Centers (#)
27
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COMMERCIALIZATION – A TWO PRONGED APPROACH
PUSH – CLINICIAN PATIENT – PULL
• Maximize success for
patients
• Thought leadership
• Business & economics
• Maximize chances of
having a baby
• High ‘pain’ of failure
• High willingness to pay
1 2
Dual Targeting for Optimal Outcomes
28
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FOR PATIENTS, MAXIMIZING SINGLE IVF CYCLE
SUCCESS IS CRITICAL
• Fresh IVF procedure cost
range $8-25K, +$20K with
additional drugs, tests1
• 2-3 cycles typical
• Large OOP* US (+60%), ES
(85%), UK (60%), DE (50%)
Pain of IVF Failure
Emotional Physical Financial
• IVF procedure is
physically demanding
with anxiety and
disappointment over
repeat cycles
1 www.FertilityIQ.com/cost March 2018 * OOP = out-of-pocket
29
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COSTS FOR AN IVF CYCLE & TYPICAL
ADDITIONAL SERVICES IN THE US
PROCEDURE COST ($)1
IVF cycle including stimulation medication 8,000 – 25,000
Additional cost items
• ICSI treatment 1,000 – 2,500
• PGT-A genetic testing 1,800 – 7,500
• Embryo freezing, yearly storage fees 200 – 800
• Cost for frozen embryo transfer 3,000 – 5,000
• Cost for using egg donor 25,000 – 30,000
• Surrogacy including all legal fees 50,000 – 100,000
• Embryo donor 5,000 – 7,000
1 www.FertilityIQ.com/cost March 2018
30
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VALUE OF NOLASIBAN DRIVEN BY IMPROVING
SUCCESS RATES & REDUCING COSTS
Significant opportunity to add value to IVF
1 www.verywellfamily.com/how-much-does-ivf-cost-1960212 March 2019; www.FertilityIQ.com/cost March 20182 www.ncbi.nlm.nih.gov/pmc/articles/PMC5584795/; Fertil Steril. 2015 May, 103(5): 1332–13393 Lemos et al. Healthcare expenses associated with multiple vs singleton pregnancies in the US. AJOG, 2013
Higher success rate135% relative (11.7% absolute) increase in live birth rate in
IMPLANT 2 means more chances for taking a baby home
Reduced number of IVF cycles2Less procedures to get a baby for same IVF investment,
i.e., each saved cycle ~$15,000 in the US1
Improving patients QoL3Higher success reduces costs from treating depression,
anxiety, & lower productivity which can cost up to $1,5002
Reduced costs from preterm
delivery of multiple pregnancies4
From 40% to 3% multiple pregnancies with incremental
preterm born costs from $80,000 (twins) to over
$350,000 (triplets)3
31
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VALUE BASED PRICE – NOLASIBAN OFFSETS
SIGNIFICANT COSTS IN IVF, US
Example based on
US LBR & costs
‒ $12.8KAssuming 55% LBR, Value
Based Price is ~ $7.7K
Unit Costs
Driver
AVERAGE COST PER IVF BABY
BORN WITHOUT NOLASIBAN
IVF
Procedure
Cost
~ $1.4K
~ $12.7K
~ $28.1K
Anxiety &
Depression
Pre-term
Multiple
Pregnancies
~ $42.3K
Total
$15,000
45% LBR
$1,500
55% failure
$80,000
18.8% MPs*
AVERAGE COST PER IVF BABY
BORN WITH NOLASIBAN
~ $26.7K
~ $1.2K~ $1.6K
IVF
Procedure
Cost
Anxiety &
Depression
Pre-term
Multiple
Pregnancies
~ $29.5K
$80,000
2% MPs*
$1,500
45% failure
$15,000
55% LBR
* MP = multiple pregnancies
Benchmark:
WAC of GONAL-F
~ $4,400 per cycle1
1 Based on IHS 2019 list
price of $2,195 for 900IU
32
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SIGNIFICANT MARKET OPPORTUNITY ACROSS
KEY GEOGRAPHIES – PEAK SALES SCENARIOS*
LOW MID HIGH
Share in Fresh (%) 15% 25% 30%
Share in Frozen (%) 15% 25% 30%
Price ($) $ 800 $ 1,100 $ 1,100
LOW MID HIGH
Share in Fresh (%) 25% 50% 50%
Share in Frozen (%) 10% 20% 30%
Price ($) $ 1,500 $ 2,000 $ 2,500
LOW MID HIGH
Share in Fresh (%) 25% 50% 50%
Share in Frozen (%) 10% 20% 30%
Price ($) $ 3,000 $ 5,000 $ 7,000
$0.0B
$0.4B
$0.8B
$1.2B
$1.6B
~ $245M
~ $590M
~ $420M
MID
~ $290M
~ $800M
~ $710M
HIGH
~ $0.45B ~ $1.2B ~ $1.8B
~ $105M
~ $220M
~ $125M
LOW* Assumes 3% year on year growth of IVF market
33
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KEY TAKEAWAYS
34
In our reach
Strong value proposition
Offsetting the pain of IVF
1
2
3
Significant opportunity4
Concentrated nature of market allows us to go it
ourselves
Nolasiban can impact the physical, mental &
financial pain of IVF
High economic value of nolasiban
Peak sales ranging from $0.5B to nearly $2B
depending on share & price assumptions
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J u l y 1 7 , 2 0 1 9
Innovating Women’s Reproductive Health and Pregnancy Therapeutics
Sett ing the Scene
CURRENT TRENDS
IN IVF AND EMBRYO
TRANSFER
35
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Infertility – a health & societal issue
9% of women 20-44 affected globally
Ageing population problematic
Too few healthy babies
Despite good quality embryos & using
best practice transfer techniques,
IVF success rate not optimal
IVF comes with a significant cost
Patients often self-fund
Payers see an unacceptably high multiple
pregnancy rate
Society pays a higher cost per healthy baby
1 WHO infertility website, April 2018. – http://www.who.int/reproductivehealth/topics/infertility/perspective/en/
U.S.: ~4.8 million women aged 20–44
Europe: ~7.2 million
women aged 20–44
Japan: ~1.6 million
women aged 20–44
China: ~22.7 million
women aged 20–44
1
2
3
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INFERTIL ITY IS A GLOBAL PUBLIC HEALTH ISSUE
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US CDC 2016 ART National Summary Report
THE NUMBER OF ART CYCLES CONTINUES TO INCREASE
Other(25,236 cycles)
Egg or embryo banking(65,840 cycles)
Fresh embryo from fresh non-donor egg(86,237 cycles)
Frozen embryo from non-donor egg(86,266 cycles)
• Total 260,000 ART cycles in 2016
• 91% used eggs or embryos
from non-donor
33% ET fresh embryos
33% ET frozen embryos
25% Banking egg or embryo
25.0%
9.6%
32.7%
32.7%
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U.S. ART CYCLES BY AGE
Source: US CDC 2016 ART National Summary Report
• 60% of patients <38 years
• Only ~20% over 40 years
Age: 43 – 44
Age: 41 – 42
Age: 35 – 37
Age: <35
Age: >44
Age: 38 - 40
19.1%
9.6%
38.3%
21.5%
6.0%
5.5%Age: 43 – 44
Age: 41 – 42
Age: 35 – 37
Age: <35
Age: >44
Age: 38 - 40
19.1%
9.6%
38.3%
21.5%
6.0%
5.5%
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(46)(44)
(47)(49)
(45)
(22)
(50) (51)(45)
(34)
(22)
(13)
(5)(9)
(50)
4% 5%
(12)
(24)
(50)
0%
20%
40%
60%
80%
100%
<35 35-37 38-40 41-42 43-44 >44
Pe
rcen
t
Age (years)
Fresh non-donor Frozen non-donor Fresh donor Frozen non-donor
TYPES OF U.S. CYCLES BY AGE
39
>95% of cycles aged <38 years were from non-donor eggs
Source: US CDC 2016 ART National Summary Report
<35 35 – 37 38 – 40 41 – 42 43 – 44 >44
96% 95% 92%
83%
67%
33%35%
65%
17%
9%
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Source: US CDC 2016 ART National Summary Report
DAY 5 ET BETTER THAN DAY 3 ET… BUT A LARGE MAJORITY OF ET STILL FAILS
Majority of embryos
were transferred on
day 5 after retrieval
0
0,1
0,2
0,3
0,4
0,5
0,6
<35 35-37 38-40 41-42 43-44 >44
Pe
rce
nt
Age (years)Day 3 Day 5
60
50
40
30
20
10
0
*Cycles using GIFT or ZIFT are excluded. Embryo transfers performed on days 1, 2, 4, and 6 are not included because
each of these accounted for a small proportion of procedures.
Percentages of Day 3 and Day 5 Embryo Transfers using fresh embryos
from fresh non-donor eggs that resulted in live births, by age group,* 2016
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Source: US CDC 2016 ART National Summary Report
ALTHOUGH SET INCREASING, 60% STILL MULTIPLE ET
Percentages of transfers
of one, two, three, or four
or more fresh embryos
from fresh non-donor eggs,
2007-2016
2007* 2008 2009 2010 2011 2012 2013* 2014 2015 2016
Pe
rce
nt
YearNumber of Embryos Transferred
One Two Three Four or more*Totals do no equal 100% due to rounding.
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• >50% of day 5 transfers with 2 or more embryos
• Relative 15% higher live birth rate
• Relative 2000% higher multiple birth rate
No. ETLive
birth %
Multiple
birth %
Single ET 50.2% 2.0%
Multiple ET 58.0% 43.8%
Four or more
0.7%
Two
48.9%
One
45.8%
Source: US CDC 2016 ART National Summary Report
MULTIPLE EMBRYO TRANSFERS SIGNIF ICANTLY
INCREASE MULTIPLE BIRTHS
Three
4.6%
42
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Source: US CDC 2016 ART National Summary Report
. . . AND NEARLY 20% OF ART L IVE BIRTHS ARE
MULTIPLE VS 2 .0% IN THE GENERAL POPULATION
Percentages of single
infants, twins, and triplets
or more among ART
transfers using fresh
embryos from fresh
non-donor eggs that
resulted in live births,
2007-2016
*Totals do no equal 100% due to rounding.
2007 2008 2009 2010 2011* 2012 2013 2014* 2015* 2016
Pe
rcen
t
Year
Single infants Twin Triplets or more
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CURRENT ART PRACTICES SUMMARY
44
• U.S. ART cycles growing, estimate ~300K annual cycles presently
• Age matters: most <38 years, smallest group >40 years
• Success rates higher for D5 vs. D3, D5 usage growing toward 70%+
• DET a poor tradeoff: 8% higher success=42% higher multiple births, but still used most often
• Overall >50% of transfers fail to result in a live birth
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TOPIC 1: PAIN OF FAILURE
45
Question:
Can you describe the financial and emotional pain of failure that your patients experience?
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TOPIC 2: INCREASING SUCCESS RATES
46
Question:
What would be considered a meaningful improvement in ET success as measured by LBR?
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TOPIC 3: DAY 5 SET TRENDS
47
Question:
What % of your ET practice is Day 5 SET, and how much could this increase?
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TOPIC 4: SET VS. DET
48
Question:
How problematic is the rate of multiple births resulting from DET, in terms of both medical risks and financial costs?
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TOPIC 5: NOLASIBAN POTENTIAL
49
Question:
Given IMPLANT 2 trial results, how would you envision nolasiban being utilized if available?