Cosmo: the future is
NOWFebruary 27th, 2018
CREDIT SUISSE LONDON ONE-ON-ONE
HEALTHCARE CONFERENCE
This presentation may include forward-looking statements that are based on our management’s beliefs and
assumptions and on information currently available to our management.
The inclusion of forward-looking statements should not be regarded as a representation by Cosmo that any of its
plans will be achieved. Actual results may differ materially from those set forth in this presentation due to the risks
and uncertainties inherent in Cosmo’s ability to develop and expand its business, successfully complete
development of its current product candidates and current and future collaborations for the development and
commercialization of its product candidates and reduce costs (including staff costs), the market for drugs to treat
IBD diseases, Cosmo’s anticipated future revenues, capital expenditures and financial resources and other similar
statements, may be “forward-looking” and as such involve risks and uncertainties and risks related to the
collaboration between Partners and Cosmo, including the potential for delays in the development programs for
LuMeBlue, and Zemcolo. No assurance can be given that the results anticipated in such forward looking
statements will occur. Actual events or results may differ materially from Cosmo’s expectations due to factors
which include, but are not limited to, increased competition, Cosmo’s ability to finance expansion plans, the results
of Cosmo’s research and development activities, the success of Cosmo’s products, regulatory, legislative and
judicial developments or changes in market and/or overall economic conditions. Cosmo assumes no responsibility
to update forward-looking statements or to adapt them to future events or developments.
You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the
date hereof, and Cosmo undertakes no obligation to revise or update this presentation.
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Safe Harbor
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2 products on the US market since,respectively, 2007 and 2013
A unique GI player in the colon space and beyond
In USD Mn, 2016: 792.1 In USD Mn, 2016: 155
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Perfectly positioned to exploit its own pipeline without need of external funding
1H 2017 in EUR Mn:
Liquidity at 7.28.2017: 136.3M (Cash & Cash Equivalent only)
Liquidity at 7.28.2017: 263.5M (Including Bonds)
Equity Ratio at 7.28.2017: 95%
Total Equity: 480.7M
Total Assets: 507.3M
End of October 2017 in EUR Mn:
Liquidity at 10.31.2017: 141.8M (Cash & Cash Equivalent only)
Liquidity at 10.31.2017: 252.3M (Including Bonds)
Equity Ratio at 11.09.2017: 94.3%
Total Equity: 471.7M
Total Assets: 500.3M
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New medical device approved in US and EU to remove colonic lesions more safely and quickly
One new product already on the market
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Methylene Blue (formerly LuMeBlue):new diagnostic drug to improve lesiondetection during colonoscopies
which have successfully completedphase III clinical trials
3 new products in the GI space and beyond
Remimazolam
Rifamycin SV (formerly Zemcolo): new antibiotic to treat colonic infections with same side effects as placebo
Remimazolam: new sedation agent to be used in all procedural sedations, including colonoscopies, safer and faster than available alternatives
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US Sales started in June 2017
Aries Inc., Commercial Organization established
45 Sales Reps, 6 Sales managers
10 Medical Science Liasons providing product support
Over 1900 accounts targeted by the Aries team
554 accounts who have ordered Eleview to date.
Market research conducted in late Sept/early Oct. shows that 74% of physicians are somehow between familiar with Eleview (from 40% right after launch), and that 79% of those familiar with Eleview are either Very Likely or Extremely Likely to use Eleview for polyps removal
Signed co-promotion deal with Olympus for US distribution, adding 200 Sales reps, 35 Clinical Education specialists and significantly increasing the number of targeted accounts
Signed distribution deal with Fujifilm for EU distribution, retaining 45% of gross revenues
Eleview 2H 2017 highlights
The future is NOW
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NDA filed July 2017
NDA accepted by FDA
PDUFA date set for May 21 2018
New dedicated plant in Lainate completed in 9 months and already inspected by FDA
Methylene Blue (formerly LuMeBlue) 2H 2017 Highlights
The future is NOW
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FDA granted both Qualified Infectious Disease Product (QIDP) and Fast Track designation for Rifamycin SV for the treatment of patients with travelers’ diarrhea
IBS-D phase II trial started October 17, 25 sites, 342 patients, first patient treated expected as of November end, trial end expected by end of 2018
New dedicated plant in Lainate completed
Dr. Falk Pharma has filed for marketing authorization of Rifafalk® 200mg (Rifamycin SV MMX® tablets) in Germany as Reference Member State through a de-centralizedprocedure. The procedure is expected to take approximately10 months
Rifamycin SV (formerly Zemcolo) 2H 2017 Highlights
The future is NOW
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Successfully completed phase III trial also in bronchoscopy, thus completing the sets of trials required for registration
NDA filing expected by the end 2018
Remimazolam 2H 2017 Highlights
The future is NOWRemimazolam
Remimazolam
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whose competing edge goes beyond patent protection
A unique pipeline
Methylene Blue: 3 yrs. regulatory exclusivity, a
diagnostic drug acting topically cannot be genericized
without evidence of increase in detection
n. 3 granted patents in the US, last expiring 2031
Rifamycin SV: 5 yrs. regulatory exclusivity as New
Chemical Entity (NCE) + 5 yrs. under the QIPD
according to the GAIN Act, for a total of 10 yrs.
Additionally, 3 yrs. regulatory exclusivity as a New
Molecular Entity (NME) + 5 yrs. under the QIDP for
the additional IBS-D indication
n. 4 granted patents on the US, last expiring 2025
Remimazolam: 5 yrs. regulatory exclusivity as NCE
n. 6 granted patents, last expiring 2033
Eleview (medical device)
n. 3 granted patents, last expiring 2034
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Provides an effective and innovative treatment option for colonic infections and offers significant anti-infective properties with a unique delivery mechanism for treatment of travelers’ diarrhea
significantly reduces TLUS in Traveller's Diarrhea
showed non-inferiority vs Xifaxan in TLUS and treatment success rates in a randomized, double-blind phase II clinical trial
TLUS was significantly shorter in Rifamycin SV compared to placebo in a randomized, double-blind phase III clinical trial
showed non-inferiority in terms of TLUS and similar efficacy, compared to Ciprofloxacin in a randomized, double-blind phase III clinical trial
Compared to Ciprofloxacin, Rifamycin SV has no systemic absorption (very important for resistance) and no warning box issues, thus being way safer in the same context
Compared to Xifaxan, Rifamycin SV allows antibiotic to be delivered directly to the colon, avoiding unwanted effects on the beneficial saprophytic bacterial flora living in the upper portions of the gastrointestinal tract; and it enjoys significantly more potent anti-inflammatory properties
Rifamycin SV (formerly Zemcolo) in a nutshell
The GI franchise beyond Lialda and Uceris
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Based on the EC50 values, Rifamycin SV is100 times more potent than Rifampicin.
Rifamycin SV is at least 1000 times more potent than Rifaximin at stimulating PXR transcriptional activity in a cell line engineered to express a fusion human PXR protein.
In terms of the maximum possible stimulation of PXR activity, Rifaximin at 30 µM only activates up to 60% of the maximum activity with Rifamycin SV at 0.3 µM.
Clear edge vs Xifaxanin anti-inflammatory properties
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The endoscopy franchise
Improve Lesion Detection
Remimazolam
Improve Lesion Removal Improve Procedure Efficiency
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Number of colonoscopies during 2017
Exploiting the colonoscopy mass market
US: 16’000’000
EU: 10’000’000
Potential ROW:
60’000’000
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Methylene Blue enhances the visualization of abnormalities and the detection of lesions by dying the entire colon prior to a colonoscopy
Increases the Adenoma Detection Rate (ADR) substantially beyond the current standard of care HDWL
This increase has an important clinical relevance: for each 1% increase in ADR, a 3% decline in incidence of interval cancer and a 5% decline in incidence of fatal colorectal cancer (CRC) has been scientifically attributed
PDUFA date set for May 21, 2018
Product features
MethyleneBlue
HDWL 200 mg
ADR 47.81% 56.29%
Relative risk increase* 17.7%
P-value 0.0099
Odds Ratio 1.41
[1.09, 1.81]
*Calculated as (ADRLuMeBlue 200 mg / ADRHDWL) - 1
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MethyleneBlue significantly enhances ADR in the full analysis set FAS
FPR HDWL
29,7%
FPR MethyleneBlue
23,3%
FP 97
Pts 326Pts 356
FP 83
MethyleneBlue decreases
FPR by 14,4% vs HDWL
p-value: < 0,0001
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MethyleneBlue FPR is significantly better than HDWL
Total MethyleneBlue pts: 485
Total HDWL pts: 479
ADR IN PTS WITH EXCISION ≤ 3
HDWL 35.9
MethyleneBlue 45.3
RRI 26.2%
ADR IN OVERALL PTS POPULATION
HDWL 47.81
MethyleneBlue 56.29
RRI 17.7%
HDWL
Pts 362 Pts 376
45.3
35.9
RRI 26.2
HDWL
Pts 485 Pts 479
56.29
47.81
RRI 17.7
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MethyleneBlue efficacy has even greater diagnostic efficacy in largest market segment
ADR IN PTS WITH EXCISION 0 - 1
HDWL 18.94
MethyleneBlue 26.18
RRI 38.2%
ADR IN OVERALL PTS POPULATION
HDWL 47.81
MethyleneBlue 56.29
RRI 17.7%
HDWL
Pts 233 Pts 264
26.2 18.9
RRI 38.2
HDWL
Pts 485 Pts 479
56.29
47.81
RRI 17.7
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MethyleneBlue shows max diagnostic value increase in the segment with 0 - 1 excision
Data from FAS
*Calculated as (ADRLuMeBlue 200 mg / ADRHDWL) - 1
HDWL 200 mg
Patients with diminutive adenomas 144 178
Percentage overall population 30.06% 36.70%
Relative risk increase* 22.1%
P-value 0.0342
Odds Ratio 1.35
[1.03, 1.76]
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MethyleneBlue flags more diminutive adenomas than HDWL
HDWL 200 mg
Pts with non-polypoid lesions 168 213
Percentage overall population 35.07% 43.92%
Relative risk increase* 25.2%
P-value 0.0056
Odds Ratio 1.45
[1.12, 1.88]
*Calculated as (ADRLuMeBlue 200 mg / ADRHDWL) - 1
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MethyleneBlue flags more subjects with non-polypoid lesions than HDWL
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Positive Remimazolam data in procedural sedation in U.S. Phase III study during colonoscopy, bronchoscopy and in III/IV ASA patients
primary endpoint and important secondary endpoints were achieved with high statistical significance
All trial data confirmed Remimazolam’s safety profile and tolerability
pre-NDA meeting with FDA before filing for approval is under planning
filing for approval expected n the second half of 2018
Product features
RemimazolamRemimazolam
Remimazolam
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Reduces Time to Reach Sedation
Medians
4.0 3.5 3.5
19.5 19.0
21.0
19.0 19.0 19.0
0
5
10
15
20
25
MOAA/S 3 Peak Sedation
Min
ute
s
Start Procedure
Placebo
Midazolam
Remimazolam
Remimazolam
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Reduces Time Back to Normal
7.2
21.3
15.7
5
0
10
15
20
25
Remimazolam Placebo Midazolam
Min
ute
s
End of procedure to fully alert
*R vs. M: Anova F-test for equal means in 2 groups
331
572 553
0
200
400
600
800
Remimazolam Placebo Midazolam
Min
ute
s
Time to back to normal
(Patient Reported)
Remimazolam
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Qolotag is a liquid, blue coloured emulsion as an enema formulation to be used for cleansing and simultaneous staining of the sigmoid colon and rectal mucosa to aid visualization of the structure and mucosal lesions by the endoscopist during flexible sigmoidoscopy evaluation
Product features allow for a faster and better enhancement of the detection of eventual small lesions or dysplasias
Long-term IBD patients generally are monitored with endoscopic system for evaluating the activity of the disease and for dysplasia detection
Cosmo intends to license Qolotag for the EU and is currently assessing the regulatory pathway for an approval in the USA
Product features
Qolotag
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an FDA 510(k)-cleared, ready-to-use submucosal injection composition, that provides an immediate and long-lasting cushion for gastrointestinal endoscopic resections of polyps, adenomas, and other lesions, is ramping up
appropriate for challenging polyps, regardless of size, location, or type and the immediate, long-lasting cushion can hold for up to 45 minutes
improves margin visibility and helps decrease the risk of gastrointestinal perforation and damage to the external muscular layer, which can lead to gastrointestinal perforation
decreases the time and volume needed to resect a lesion while reducing both reinjections required and piecemeal excisions, as compared to saline
Addressing the US market with Olympus and EU with Fujifilm
Product features
Eleview
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Unique &Novel Mechanism
Upon injection:
Eleview®: Reconfigures to form a colored cushion1
Creates an “artificial net” formed by polymer chains2
Traps water within to build a colored cushion of
optimal shape, height, and duration1
1 Eleview® Instructions for use, Aries Pharmaceuticals, Inc. April 2017
2 Data on File, Aries Pharmaceuticals, Inc.
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Outline of trial primary endpoints all in favor of Eleview
Endpoint StatisticsEleview®
(N=102) (n=102)
Reference Comparator
(N=109) (n=110)
Total injected volume to
complete EMR procedure (mL)
Mean (±SD) 16.1 (±9.8) 31.6 (±32.1)
Range (min-max) 3.0 – 41.0 4.0 - 248.0
P value < 0.001
Total injected volume per
lesion size (mL/mm)
Mean (±SD) 0.53 (±0.32) 0.92 (±0.65)
Range (min-max) 0.09 – 1.75 0.20 – 4.96
P value < 0.001
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Outline of trial primary endpoints all in favor of Eleview (CONTD)
Endpoint StatisticsEleview®
(N=102) (n=102)
Reference
Comparator
(N=109) (n=110)
Time to resect the lesion
(minutes)
Mean (±SD) 19.15 (±16.80) 29.70 (±69.18)
Range (min-max) 1-100 2-687
% differenceª -35.5%
P value 0.326
aEleview® vs reference comparator.
This can be attributed to the high variability of data, particularly in the reference comparator arm (SD Eleview® = 16.80 m; SD reference comparator =69.18 m → 4 times increase)
Nevertheless, it is evident that there is a positive trend toward a reduction of the time needed to complete the procedure
using Eleview®with respect to comparator: reduction of 35.5% (10.6 minutes/procedure). This trend is confirmed by the
whole colonoscopy time (one of the secondary end points)
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Outline of trial Secondary endpoints all in favor of Eleview
Endpoint StatisticsEleview®
(N=102) (n=102)
Reference Comparator
Eleview® n (%)
Sidney Resection Quotient
(SRQ)
Mean (±SD) 10.3 (±8.1) 8.0 (±5.7)
P value 0.044
Number of resection piecesMean (±SD) 5.70 (±6.03) 6.47 (±5.04)
P value 0.052
Injected volume to provide
initial lift (mL)Mean (±SD) 10.4 (±7.0) 15.3 (±11.7)
P value < 0.001
Proportion of subjects with
en bloc resections N(%)Mean (±SD) 19 (18.6%) 12 (11.0%)
P value 0.125
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Complication Eleview® n (%)Reference Comparator
Eleview® n (%)
Subject with at least one complication 17 (15.0) 17 (15.2)
Intraprocedural bleeding
Early (<24h) bleeding
Delay bleeding (≥24h post EMR)
Perforation
Postpolypectomy syndrome
Hospital admissions for any post
procedural clinically relevant complication
8 (7.1)
2 (1.8)
0 (0.0)
0 (0.0)
6 (5.3)
1 (0.9)
11 (9.8)
1 (0.9)
1 (0.9)
1 (0.9)
3 (2.7)
0 (0.0)
Eleview is as safe as the standard saline solution
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FY17 Operating Expenses of $40m
Prelaunch Plans for mid-year launch of MB and Rifamycin SV are being implemented
Sales force expansion planned following MB approval – likely an additional 110 sales reps plus managers will be added
All Sales Reps (~155) are expected to promote all three products (Eleview, MB and Rifamycin SV)
Prelaunch planning for a 2019 launch of Remimazolam has begun
An additional expansion of the sales force to support Remimazolam is being evaluated
Update on Aries set-up
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File Rifamycin SV NDA
Extend Eleview deals to RoW
Start treating patients in Rifamycin SV IBS-D phase II
File Remimazolam NDA
Further expand pipeline
Next steps:
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Cosmo Pharmaceuticals NV
Riverside II
Sir John Rogerson’s Quay
Dublin 2, Ireland
Mr. John Manieri
+353 1 817 03 70