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©The Medicines Company 2018 1›
Oppenheimer28th Annual Healthcare Conference
Clive Meanwell • Chief Executive Officer
Safe HarborForward-looking statements
©The Medicines Company 2018 2
Statements in this presentation about The Medicines Company (the Company), the Company’s products and product candidates, the timing of clinical trial results, regulatory submissions, product or indication launches, the Company’s strategy, future financial results and operations, and future opportunities for the Company, that are not purely historical, and all other statements that are not purely historical, may be deemed to be forward-looking statements for purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words “believes," “anticipates," “plans,“ “expects," “intends," “estimates," “potential," “outlook,” “may,” “will,” “would,” and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause actual results or events to differ materially from those indicated by such forward looking statements, including:
whether the Company’s product candidate will advance in the clinical trials process on a timely basis or at all; whether clinical trial results will warrant submission of applications for regulatory approval; whether the Company’s product candidate will receive approvals from regulatory agencies; the extent of the commercial success of the Company’s product candidate, if approved; and such other factors as are set forth in the risk factors detailed from time to time in the Company’s periodic reports filed with the Securities and Exchange Commission (SEC) including, without limitation, the risk factors detailed in the Company’s Annual Report on Form 10-K filed with the SEC on March 1, 2018, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements whether as a result of new information, future events or otherwise
Why are we here?Our purpose
Solve major challenges in healthcare and create enormous value
Focus on atherosclerotic cardiovascular disease, the foremost cause of death and greatest health burden
− Leverage Nobel-prize-winning science, technology and data
− Devise trustworthy, human-centric solutions
− Create significant value for shareholders and other stakeholders
Where are we?Our situation
Inclisiran in Phase IIIa / IIIb program moving aggressively
Validated plans and people in place
− Pivotal trials advancing rapidly to NDA/MAA
− Commercial scale manufacturing achieved
− CVOT set up to show low NNT for MACE and mortality benefit
− Unprecedented pricing flexibility and value demonstration opportunity
Product development track record and capabilities
Strong financial position
InclisiranInvisible, silentSM
Inclisiran
Proven scientific foundationsInvisible, silent
©The Medicines Company 2018 7
Proven scientific foundations for inclisiranStanding on the shoulders of others
Large global population in need of LDL-C lowering
LDL-C an unambiguous cause of ASCVD
PCSK9 proven therapeutic target for LDL-C and outcome improvement
Inclisiran unique therapeutic attributes emerging rapidly
Since this conference began ~1,000 people died of ASCVD
Another 39,000 will be dead by this time tomorrow
©The Medicines Company 2018 8
©The Medicines Company 2018 9
Proven scientific foundations for inclisiranEnormous population with recognized needs (many more unrecognized)
Patients with raised LDL-C on any treatment(Millions of patients)
US EU5 Japan Total
Primary prevention (>100 mg/dL) 16 20 8 44
Secondary prevention (>70 mg/dL) 23 23 10 56
FH 0.9 0.9 0.4 2.2
Treated with lipid-lowering Rx 40 44 18 102
©The Medicines Company 2018 10
Proven scientific foundations for inclisiranEven perfect data, organization and activation will leave millions at risk
Treated optimally (HI statin + EZ) but still not reaching LDL-C goal(Millions of patients)
US EU5 Japan Total
Primary prevention (goal 100 mg/dL) 1.2 1.4 0.6 3.2
Secondary prevention (goal 70 mg/dL) 3.4 3.4 1.5 8.3
FH 0.9 0.9 0.4 2.2
Optimally treated by still not at goal 5.5 5.7 2.4 13.7
©The Medicines Company 2018 11
Proven scientific foundations for inclisiranLDL-C the unambiguous cause of ASCVD
Ference B, et al. Eur Heart J. 2017;38:2459-2472.
Animal data
LDL-C induces atherosclerosis
Specificity
Independent risk factor
Genetics
LDL-C variants confer risk
Consistency
Invariant outcomes
Biological gradient
Proportional risk
Coherence
Clear correlation
Sequence
LDL-Cthen ASCVD
Intervention
Lowering LDL-C reduces events
Proven scientific foundations for inclisiranPCSK9 regulates LDL-R function and therefore LDL-C levels
LDL-R PCSK9 LDL-C
Statins
PCSK9inhibition
Proven scientific foundations for inclisiran
©The Medicines Company 2018 13
1: Ference B, et al. NEJM 2016:375:2144-2153. 2: Cohen J, et al. NEJM 2006;354:1264-1272. 3: Sabatine M, et al. NEJM 2017;376:1713-1722. 4. Steg G ACC.18
PCSK9 carries the essential modern hallmarks of a therapeutic target
Mendelian randomization1 Genetics2 Therapeutic intervention3,4
-0.40 -0.30 -0.20 -0.10 0 0.10
0.81 (0.74–0.89) for each 10 mg/dL LDL-C reduction
0
4
8
12
No Yes
Co
ron
ary
He
art
Dis
ea
se (
%)
PCSK9142X or PCSK9679X
Inclisiran’s unique therapeutic attributes are emerging rapidly
©The Medicines Company 2018 14
Inclisiran attributes emerging rapidlyDose-dependent LDL-C sustained over one year
©The Medicines Company 2018 15
Ray KK et al. NEJM 2017; 376: 1430-40.
Days from first injection
p-value for all comparisons to placebo <0.0001
Me
an
pe
rce
nt c
ha
ng
e (±
95
% C
I)
-60
-50
-40
-30
-20
-10
0
10
0 30 60 90 120 150 180 210 240 270 300 330 360
Placebo 100 mg
200 mg 300 mg
56% 53%
Inclisiran attributes emerging rapidlyConsistent responses as anticipated by mode of action
©The Medicines Company 2018 16
Ray KK et al. NEJM 2017; 376: 1430-40.
-140
-110
-80
-50
-20
10
40
Ch
an
ge i
n L
DL
-C (
mg
/dL
)
39 mg/dL (1mMol/L)
78 mg/dL (2mMol/L)
Background treatment + Inclisiran 300 mg
All patients responded
Mean -64.2 mg/dL
Max -122.0 mg/dL
Inclisiran attributes emerging rapidlyHow to get 20-30% fewer second ASCVD events
0
20
40
60
80
100
120
140
0 30 90 150 210 270 330 390 405 510 570 630
LD
L-C
(m
g/m
L)
Time (months)
©The Medicines Company 2018 17
Output of a simultaneous PD model using all Phase II data and mechanistic inputs
0 6 12 18
Average LDL-C reduction 55%
300 mg inclisiran given twice a year
Inclisiran attributes emerging rapidlyHow to get 20-30% fewer second ASCVD events
LDL-C levels (mg/dL) Anticipated CV outcomes
Baseline 55% Treated level annualized risk reduction1
150 83 68 50%Typical
baseline in clinical
trials
125 69 56 41%
100 55 45 33%
75 41 34 25%
50 28 23 17%
1: Assumes 5 years observation
Inclisiran attributes emerging rapidlyHow to get 30 more years in primary prevention
0
20
40
60
80
100
120
140
0 30 90 150 210 270 330 390 450 510 570 630
LD
L-C
(m
g/m
L)
Time (months)
©The Medicines Company 2018 19
Output of a simultaneous PD model using all Phase II data and mechanistic inputs
0 6 12 18
Average LDL-C reduction 43%
300 mg inclisiran given once a year
Inclisiran attributes emerging rapidlyHow to get 30 more years in primary prevention
1 20 40 60 80 100
5
10
0
+30 years
CumulativeLDL-C
(g/dL-years)
Age (years)
Threshold for ASCVDLDL -/- PCSK9 +/-
Inclisiran 300 mg annually
-40%Ø 63 mg/dL
NormalØ 105 mg/dL
Inclisiran attributes emerging rapidlyBiological leverage of RNAi translates into real-world efficiency
* 90% of Repatha patients use SureClick® auto-injector 26 times per year; 10% use Pushtronex® system 12 times per year (IMS)
Amount Devices Temperature
Inclisiran
600 mg/yr 2 Room temperature
mAb
2-5 g/yr 26* Refrigerated
©The Medicines Company 2018 22
Inclisiran attributes emerging rapidlyShipped and stored at room temperature
6.0
7.0
8.0
9.0
10.0
11.0
12.0
100
120
140
160
180
200
220
0 10 20 30
Room temperature stability
Assay pH
Ass
ay
(mg
/mL
)
pH
Month
Prefilled syringe
Auto-injector
Inclisiran attributes emerging rapidlyManufacturing established at commercial scale
Synthesis established, automatable and high quality
− Capacity and scalability
Boulder, CO Frederick, CO
Phase IIIa pivotal LDL-C lowering trials with 18-months treatment have completed enrollment
Phase IIIa program for NDA-MAA in LDL-lowering18-months treatment trials have completed enrollment
Study Countries Main inclusion criteria Baseline LDL-C Patients
ORION-9 US, EU, SA Heterozygous FH 482
ORION-10 US ASCVD secondary prev. >70 mg/dL 1,561
ORION-11 EU, SA ASCVD secondary prev.High risk primary prev.
>70 mg/dL>100 mg/dL
1,617
Total 3,660
Phase IIIa program for NDA-MAA in LDL-loweringEmerging safety and tolerability profile
DSMB un-blinded review (March 2018)
− 2,332 patients
− Recommended continuation of Phase III studies with no changes
Ongoing review of blinded data (>3,400 patients incl. >2400 day 30)
− Very low incidence of reported mild, transient skin reactions
− No reports of significant LFT or other laboratory abnormalities
©The Medicines Company 2018 26
Phase IIIa program for NDA-MAA in LDL-lowering
©The Medicines Company 2018 27
Anticipated 10-fold increase in safety information during 2018
Rapid accumulation of safety data
− Now adding 10 patient years per day
Anticipate 10-fold increase during 2018
− ~1,700 with 3 doses
− ~300 with 4 or 5 doses
Accumulating patient-years of safety data
0
500
1000
1500
2000
2500
Phase I Phase II Phase III byend-2018
Phase IIIb cardiovascular outcomes trial in secondary ASCVD prevention is set to start enrolling in 2H 2018
Phase IIIb program for cardiovascular outcomesORION-4 is a streamlined secondary prevention clinical trial
Key design elements:
− Baseline LDL-C ≥100mg/dL
− Primary endpoint CHD death, MI, ischemic stroke, urgent revasc.
− Secondary endpoints include CHD and CV death
− Median follow-up 5 years
− 15,000 patients
OutcomeAssumed annual event rate
for placeboPower
(2P<0.01)Power
(2P<0.05)
MACE 2.7% >99% >99%
CHD death or MI 1.7% 99% >99%
CV death 0.9% 90% 97%
Phase IIIb program for cardiovascular outcomesORION-4 is powered for both primary and secondary endpoints
High quality inclisiran program moving quicklyNDA/MAA anticipated for submission by year end 2019
©The Medicines Company 2018 31
2012 2013 2014 2015 2016 2017 2018 2019 2020 2021
13 March
Demonstrate marketability
Confirm performance
Prove therapeutic concept and technical feasibility
Discover and develop technology
PCS iv
CV outcomes
PCSsc Pre-clinic
Phase I Phase II NDA/MAA review
CMC development
Launch
Commercial manufacturing
Phase III LDL-C
Inclisiran development to NDA and MAAAnticipated news flow 2018
First half Second half
Second DSMB review Further DSMB reviews
First patients dosed in ORION-5 Pre-filled syringe switch over in pivotal trials
Publications including ORION-1 subgroups
ESC, ADA, AHA
FinancialsSufficient funding to move deliver inclisiran development plans
Anticipate available cash & liquidity sufficient to complete
− Phase III clinical trials
− Manufacturing scale up
− NDA-MAA submission
− CVOT recruitment
What to expect from usInclisiran moving forward rapidly in a high quality innovation program
Anticipate the leading product profile in the largest pharmaceutical market
Highly-differentiated from existing lipid-lowering products
− Unique attributes
− Unprecedented performance
− Highest value to patients, providers and payers
Significant news flow and catalysts in 2018
Firm-wide focus on maximizing shareholder value
Q&A