Medicure Inc (MPH) Quote

n

nn

nn

[Suppressed Sound Link]

I've heard they have some good stuff up there in Canada,,,doe'jah know Aye!!!!

d;o)

=»} EZ BUD!!!!

what do they have that anyone would want to buy

are you handling the negotiations?

~*~MCU~*~LOOKS LIKE A "NOBRAINER"!!!IMO!!!

>>>Street buzz picking up now buyout talk etetc could uptick on impulse,,,we bee$ a'watch"in' fur one easy flip,,, rrr'mm hopefully 5+ Bagger(50¢->$1???)!!!~fwiw~

:)

EZ!

I guess uddurr cuntreez gonna cop some drugs from MMed!cure?*LOL*

>>>WUHAYADDAKNØWBØUTDAT?????


?~:))

BLESS!!!

Should see a nice pop here bud! Snagged up a BIG chunk @ 11¢ locked n' loaded~>ready fo' da ride!!!

*>* MCU*>* DD=

http://www.invasivecardiology.com/article/993


<<<

Looks way undervalued @ current PPS...imho!

:)

eZ^!

YO D!!!! Grabbed some off bottom here,,,looks good for a bounce,,,should see a build-up with shorts covering and longs dubbin' down from $1 on anticipation of forthcoming PR!!!!~imho!~

*WATCH*

:))

~EZ!!!!!

http://www.careerbuilder.com/monk-e-mail/Default.aspx?mid=25275667&cbRecursionCnt=1&cbsid=e8ed302fb7f3470baa032dcd99db97f4-252410903-RL-4

ma
http://finance.yahoo.com/q/mh?s=SQNM

http://phx.corporate-ir.net/phoenix.zhtml?p=irol-eventDetails&c=84955&eventID=1637625

http://google.brand.edgar-online.com/fetchFilingFrameset.aspx?FilingID=5485360&Type=HTML

http://phx.corporate-ir.net/phoenix.zhtml?p=irol-eventDetails&c=84955&eventID=1637625

Thomas Weisel Partners and its affiliates do and seek to do business with companies covered in its research reports. As a result, investors
should be aware that the firm may have a conflict of interest that could affect the objectivity of this report. Customers of Thomas Weisel
Partners in the United States can receive independent, third-party research on the company or companies covered in this report, at no cost
to them, where such research is available. Customers can access this independent research at www.tweisel.com or can call (877) 921-3900 to
request a copy of this research. Investors should consider this report as only a single factor in making their investment decision.
Please see analyst
certification and other
important disclosures
starting on page 9 and
continuing through
page 10.
MEDICURE INC. —MCU
CLOSE TO THE HEART
Overweight AMEX: $1.42 as of 7/31/07
Initiation Report
Key Data FY 2006 2007 2008
52-Week Range: $1 - 2 EPS
Market Cap. (mn): $165.1 1Q $(0.05)A $(0.03)A $(0.06)E
Shares Outstanding (mn): 116.3 2Q $(0.04)A $(0.06)A $(0.03)E
Average Daily Volume: 95,410 3Q $(0.03)A $(0.06)A $(0.02)E
Free Float (mn) 105.4 4Q $(0.03)A $(0.08)E $(0.02)E
Short Int. (% Free Float) 0.0 Year $(0.15)A $(0.23)E $(0.13)E
Fiscal Year End: 5/31 P/E NM NM NM
Revenue (mn)
Total Debt/Equity 34% 1Q $0.03A $0.25A $4.04E
TEV/TTM Sales: 41.0x 2Q $0.03A $1.26A $4.93E
Net Cash/Share: $0.13 3Q $0.05A $2.16A $5.72E
Book Value/Share: $0.27 4Q $0.15A $3.12E $6.29E
Price/Book Value: 5.4x Year $0.26A $6.79E $20.98E
Price Target $3.00 TEV/Sales NM 23.1x 7.5x
Source: Company reports, Thomson Financial and Thomas Weisel International estimates
Note: Medicure Inc. reports in CN$ we have used convenience translation into US$ equivalents. Price is as of the close on the date
indicated. Any price target displayed in the data box above represents either a specific price target or the midpoint of a range. EPS are pro
forma for stock-based compensation expense and one-time items.
• We are initiating research coverage of Medicure Inc. (MCU) with an Overweight rating and
a 12-month price target of $3.
• Growing Aggrastat sales; near-term phase III data on MC-1: Medicure is a cardiovascular drug
company. It has acquired and started marketing Aggrastat, a GPIIb/IIIa inhibitor. Lead pipeline
drug MC-1 is currently in a pivotal phase III study in coronary artery bypass graft (CABG) patients.
• Aggrastat set to recover; peak sales to cross $100mn: We believe that Aggrastat will recapture
significant market share in light of focused marketing efforts and an active salesforce. We estimate
peak sales to cross $100mn by 2015.
• MC-1 phase II data indicative of efficacy; likely to meet phase III endpoints: MEND-1 and
MEND-CABG phase II study results were clearly indicative of the cardio-protective properties of
MC-1. Based on that, we believe that the endpoints in the MEND-CABG II phase III studies are
likely to be met. We expect a mid-2009 launch of the drug and estimate that peak sales will reach
$700mn if additional indications of angioplasty and acute coronary syndrome are approved.
• Valuation: We obtained our 12-month price target of $3 by applying a 30x P/E multiple to our
2012 pro forma EPS estimate of $0.20 and discounting it back at 20%. There are always risks that
the price target for any security will not be realized. In addition to general market and
macroeconomic risks, for Medicure, Inc., these risks include, among other things, clinical trial
failure of its ongoing MC-1 development programs and competition from bigger pharmaceutical
companies.
August 1, 2007
HEALTHCARE
Biopharmaceuticals
Bino Pathiparampil
415.262.6365
Bpathiparampil@tweisel.com

August 1, 2007 Thomas Weisel International
2 Bino Pathiparampil 415.262.6365
CARDIOVASCULAR DRUG DEVELOPER WITH IMPRESSIVE PORTFOLIO
One product in market; high potential product in phase III; rich pipeline:
Medicure, Inc, located in Winnipeg, Manitoba, focuses on developing therapeutics for
the treatment of cardiovascular diseases. Aggrastat, Medicure’s sole product on the
market, was acquired from MGI Pharma in August 2006 and is used in patients
undergoing invasive cardiac procedures such as angioplasty. The company has one drug
currently in phase III studies to prevent ischemic injury in coronary artery bypass graft
(CABG) patients and two other clinical stage drugs—one in phase II for treatment of
hypertension in diabetics and another in phase I to treat hypertension in patients with
metabolic syndrome.
Aggrastat set to recover; peak sales could cross $100mn: Aggrastat (tirofiban
hydrochloride), a GPIIb/IIIa inhibitor, is used for the treatment of acute coronary
syndrome (ACS) and as an adjuvant to percutaneous transluminal coronary angioplasty
(PTCA) or atherectomy. After several years of languishing sales as a result of inadequate
marketing efforts, Aggrastat was acquired in the United States by Medicure. Its newly
formed, 25-person-strong salesforce is working actively and turning around the product.
We believe that Aggrastat can improve its market share significantly and we estimate that
peak annual sales will cross $100mn by 2015. Total U.S. sales for GPIIb/IIIa inhibitors,
including Reopro (abciximab) marketed by J&J and Integrilin (eptifibatide) marketed by
Schering Plough, totaled $430mn in 2006 (a 0.1% increase y/y), with Aggrastat
accounting for only $8.6mn. In the EU, however, where Merck actively markets the
product, Aggrastat has a significant market share and commands sales comparable to
those of Integrilin. Available data comparing the three GPIIb/IIIa inhibitors suggest that
Aggrastat is as efficacious as Reopro and Integrilin, with some added advantages.
Aggrastat is currently being evaluated in several clinical studies by Merck. Data from an
Italian study comparing Aggrastat with Reopro is expected in the spring of 2008. We
estimate Aggrastat FY07 U.S. sales of $6.79mn.
MC-1—fast-track status and SPA agreement with the FDA: MC-1, a vitamin B6
metabolite, has significant cardio-protective effects that can mitigate the effects of
reperfusion injury. Reperfusion injury occurs when blood flow to the heart muscle cells is
restored after a period of ischemia, leading to a flurry of cell-damaging immune
mediators. This typically happens in the setting of a coronary artery bypass graft
(CABG), PCTA and thrombolysis in ACS. MC-1 was granted fast-track status with the
FDA as a treatment to reduce cardiovascular and cerebrovascular events associated with
ischemic and/or ischemic reperfusion injury in patients undergoing angioplasty, CABG
surgery and in ACS.
$1bn potential opportunity; serving an unmet medical need: According to the
American Heart Association (AHA), approximately 400,000 CABG and 1.4mn
angioplasty procedures were conducted in the United States in 2006. There is currently
no cardio-protective drug available against reperfusion injury resulting from these
procedures. Assuming a per-patient cost of $600 for MC-1, this could represent a $1bn
opportunity, should the drug receive FDA approval.

August 1, 2007 Thomas Weisel International
3 Bino Pathiparampil 415.262.6365
MC-1 Phase II data suggestive of efficacy: In the 60-patient, MEND-1 phase II
study, MC-1 reduced the median area under the periprocedural CK-MB curve (AUK)
from 32.9ng/ml to 18.6ng/ml (a 43.5% reduction; p=0.038) on post-operative day 30
(POD30). It also showed a good safety profile. In the 900-patient, placebo controlled,
multi-dose MEND-CABG study, MC-1 achieved a 37.2% reduction in the composite
endpoint, with myocardial infarction (MI) defined as peak CK-MB ≥100ng/ml, in the
250mg arm versus placebo (p=0.028). The composite endpoint consisted of death, non-fatal
MI and non-fatal stroke. In addition, there was also a 46.9% reduction in the
incidence of non-fatal MI (peak CK-MB band ≥100ng/ml) in the 250mg MC-1 group.
MC-1 also achieved a 31.7% reduction in the composite end, with MI defined as peak
CK-MB ≥70ng/ml, in the 250mg arm versus placebo (p=0.035). The POD30 findings
of significant reduction in the composite endpoint continued to POD90; however, MC-1
could not establish significant improvement in the composite endpoint versus placebo
when MI was defined as peak CK-MB ≥50ng/ml. Also, the 750mg arm performed
worse than the 250mg arm; the company explains this as a result of the peaking of
plasma levels of MC-1 followed by accelerated excretion from the body. The compound
exhibited a good safety profile in the study.
MEND-CABGII phase III study ongoing; expect results in 1H08: MC-1 is
currently being studied in a 3,000-patient, double-blind, randomized, placebo-controlled
phase III trial, the MEND-CABG II study. This trial is being conducted in 120 centers
across the United States, Canada and Germany, and results are expected in 1H08. The
primary endpoint is a reduction in a composite of death and nonfatal MI (peak CK-MB
band ≥100ng/ml) up to POD30 compared to placebo. We believe that the trial has a
good chance of meeting its endpoint and expect a mid-2009 launch. We estimate that
peak annual sales could exceed $700mn if the other indications (PTCA and ACS) are also
approved. The company intends to conduct future label expansion studies in ACS and
stroke patients
RICH PIPELINE ADDS TO THE PROMISE
Satisfactory MC-4232 phase II data: phase III study pending: According to the
Centers for Disease Control and Prevention (CDC), more than 14mn Americans are
currently living with diabetes with another 6.2mn undiagnosed with the disease. Of those
diagnosed with diabetes, around 73% suffer from hypertension. MC-4232 is a
combination of MC-1 and lisinopril, an ACE inhibitor, and was recently evaluated in a
phase II trial, the MC-1 and ACE Therapeutic Combination for Hypertensive Diabetics
(MATCHED) study. Results from this study showed that MC-4232 reduced mean
daytime ambulatory systolic blood pressure (MDASBP) by 4.5mm Hg more when
compared with the use of lisinopril alone and reduced fasting serum glucose by
1.45mmol/L. No statistically significant decrease in HbA1c levels was seen, however.
The company intends to conduct a 1,500-patient phase III study, but further
development is currently on hold until results are available from the MEND-CABG II
study.
Good early stage drugs in MC-4262 and MC-4538: Other drugs in the pipeline
include MC-4262 (a combination of MC-1 and an angiotensin II receptor blocker (ARB))
currently in phase I for treatment of hypertension in individuals with metabolic

August 1, 2007 Thomas Weisel International
4 Bino Pathiparampil 415.262.6365
syndrome. Medicure is also developing a novel compound, MC-4538 which is currently
in preclinical evaluation for use as an anti-thrombotic agent.
MCU Pipeline
Products
Aggrastat ®
Acute Coronary Syndrome (ACS)
MC-1
Coronary Artery Bypass Graft (CABG)
Acute Coronary Syndrome
Stroke
MC-4232
Diabetic Hypertension
MC-4262
Hypertension Complicated
with Metabolic Syndrome
MC-45308
Thrombosis
MC-5422
Ischemia DISCOVERY
Source: Company reports
Approval Market Preclinical Phase I Phase II Phase III
COMPANY INSIGHTS
Experienced management: Dr. Albert Friesen, Medicure’s founder and CEO, has
been with the company since its inception in 1997. Prior to that, he held senior
management positions in several companies such as Viventia Biotech and Genesys
Pharma. He also played a significant role in the founding and successful sale of
companies including Rh Pharmaceuticals (acquired by Cangene) and ABI Biotechnology
(acquired by Apotex). Other senior management includes personnel with several years of
significant industry experience.
Good cash position: Medicure ended 3Q07 with more than $37mn in cash. Based on
our estimates, the company will be able to make it through late 2008 with the current
drug development plans. Medicure raised approximately $25mn in December 2006 via a
private placement of common stock at a price of $1.30 per share, in addition to the
issuance of approximately 4mn warrants.
Key shareholders: Major shareholders of Medicure include Columbia Wanger Asset
Management, L.P. (7.94%) and Dr. Albert Friesen (6.59%).
ESTIMATES
Our 4Q07 and FY07 revenue and pro forma estimates are $3.12mn and $(0.08) and
$6.79mn and $(0.23), respectively. Our FY08 revenue and pro forma estimates are
$20.98mn and $(0.13), respectively.

August 1, 2007 Thomas Weisel International
5 Bino Pathiparampil 415.262.6365
POTENTIAL UPSIDES TO OUR ESTIMATES
MC-1 label expansion; off-label use: Our current estimates for MC-1 only include
revenue from its use in CABG procedures. There could be significant upside potential to
our estimates should the drug be used for patients undergoing angioplasty procedures
and in ACS patients.
FDA approval of MC-4232: Our current revenue estimates do not include sales of MC-4232,
since further development of the drug is currently on hold. If results from the
planned 1,500-patient trial turn out positive and the drug receives FDA approval, there
would be significant upside to our revenue estimates.
POTENTIAL DOWNSIDES TO OUR ESTIMATES
Failure of MC-1 phase III trial: All of Medicure’s resources are currently directed
toward the MC-1 MEND-CABGII trial. Failure of MC-1 to demonstrate significant
benefit in the phase III trial would result in significant downside to our estimates.
Inability of the sales force to deliver: Medicure competes in the cardiovascular space
currently dominated by large pharmaceutical companies. Should the salesforce be unable
to gain a foothold in the market, this could result in lower revenue and downside to our
estimates.
Medicure, Inc - Near-Term Milestones
Drug Indication Milestone Timing
Aggrastat ACS Data from four ongoing clinical studies 2Q08
MC-1 CABG Phase III data 2Q08
MC-4232 Hypertension in Diabetics Initiation of phase III study 2H08
Source: Company reports and Thomas Weisel International estimates
RISKS
Drug development risks: All drug development programs carry an inherent risk of
failure by virtue of the unpredictable nature of clinical trial results and could result in
significant financial loss in terms of resources spent on the program.
Market risk: Medicure’s drug serves an unmet medical but will cater to the
cardiovascular market, which is highly dominated by large pharmaceutical companies.
Medicure could face intense competition from these firms with bigger salesforces,
especially in relation to Aggrastat.
VALUATION
We obtained our 12-month price target of $3 by applying a 30x P/E multiple to our 2012
pro forma EPS estimate of $0.20 and discounting it back at 20%. There are always risks
that the price target for any security will not be realized. In addition to general market
and macroeconomic risks, for Medicure, Inc., these risks include, among other things,
clinical trial failure of its ongoing MC-1 development programs and competition from
bigger pharmaceutical companies.

New Clinical Trials Evaluate High-Dose AGGRASTAT(R) in High-Risk Patients

This is an old study but a quote from Eric Topol is important to explain the study that basically killed the sales of this drug when Merck owned it in the US.

Eric Topol, M.D. of the Cleveland Clinic Heart Center explains, "This study provides further support for doing a repeat large-scale trial testing tirofiban versus abciximab, since so much data now suggest the bolus dose we used (for tirofiban) in TARGET was inappropriately low." In the Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial (TARGET) trial, tirofiban was given at 10 mcg/kg bolus followed by a 0.15 mcg/kg/min infusion for 18 to 24 hours.

Merck used the wrong dose in the target trial. Here are the results.

TARGET
In the first study to compare the effects of 2 platelet glycoprotein IIb/IIIa inhibitors, researchers compared tirofiban (Aggrastat) to abciximab (ReoPro), said Eric Topol, MD, chairman of cardiology at the Cleveland Clinic Foundation. The trial included 4812 patients at 149 hospitals in 18 countries throughout North America, Europe, and Australia who were scheduled for an interventional procedure including a stent.

In the study, 2398 patients were assigned to tirofiban and 2414 to abciximab. The end point at 30 days was death, myocardial infarction, or urgent target vessel revascularization. In the tirofiban group, 7.55% of patients reached one of the end point situations. In the abciximab group, 6.01% of patients reached the end point. Dr Topol said the difference was 26% favoring abciximab—a statistically significant finding. The study concluded that the preferred agent for coronary stenting was abciximab at the 30-day end point. In a released statement, Rick Sax, MD, senior director of clinical research at Merck Research Laboratories said, "Merck remains firm in its commitment to the use of Aggrastat when it is indicated in patients presenting to the hospital with acute coronary syndromes, including patients who subsequently go on to have an angioplasty procedure. The benefits of Aggrastat in improving outcomes in these patients were firmly established in the PRISM-PLUS study." Merck sponsored the TARGET trial.




BALTIMORE, July 29 /PRNewswire-FirstCall/ -- Guilford Pharmaceuticals,
Inc. (Nasdaq: GLFD) today announced the publication of two new clinical trials
of AGGRASTAT(R) that evaluated the safety and efficacy of high-dose
AGGRASTAT(R) Injection (tirofiban hydrochloride) in patients undergoing
primary coronary angioplasty for ST segment elevation myocardial infarction
(STEMI) and high-risk coronary angioplasty. These trials used a new dosing
regimen of AGGRASTAT(R)
(25 mcg/kg bolus over 3 minutes followed by infusion at 0.15 mcg/kg/min for
18 hours) and compared this regimen to abciximab (ReoPro(R)) or placebo.
AGGRASTAT(R), in combination with heparin and aspirin, is indicated for
the treatment of acute coronary syndrome (ACS) including patients who are to
be managed medically and those undergoing PTCA or atherectomy.
Results from the first trial known as ADVANCE, published in the Journal of
the American College of Cardiology(1) yielded a significantly reduced primary
composite end point (death, nonfatal MI, urgent TVR, and bailout GP IIb/IIIa
inhibitor therapy during follow-up) with heparin plus tirofiban over heparin
plus placebo [20% vs. 35%, respectively (hazard ratio 0.51, 95% confidence
interval 0.29 to 0.88; p = 0.01)]. This double-blind, placebo-controlled,
randomized trial included 202 high-risk patients undergoing percutaneous
coronary intervention (PCI).(2) In this trial, 98% of patients underwent
stenting. Any stent type approved by a regulatory agency could be implanted.
All patients were pretreated with aspirin (160 to 325 mg orally) and
thienopyridine (ticlopidine 500 mg as a loading dose and then 250 mg twice
daily or clopidogrel 300 mg orally as a loading dose and then 75mg/day at
least 48 or 6 hours before the procedure).
Investigators conclude that high-dose bolus tirofiban plus heparin was
safe and effective in this study. Minor bleeding was observed in both the
tirofiban and placebo arms; the difference between the two was not
statistically significant (p=0.19). There was no severe thrombocytopenia in
either treatment, and one patient in each treatment arm had mild
thrombocytopenia.
"These data suggest that high-dose tirofiban can reduce the frequency of
major adverse cardiovascular events in high-risk patients undergoing PCI,"
says Matthew Meldorf, M.D., Senior Director, Medical Affairs of Guilford
Pharmaceuticals. "We are encouraged by these data and are evaluating our
options for pursuing additional large-scale trials to confirm these results."
Findings from a randomized study of 100 patients, published in the
American Journal of Cardiology(3) suggest high-dose bolus tirofiban may be as
effective as abciximab for 30-day recovery of left ventricular function (as
the primary endpoint) in patients undergoing primary coronary angioplasty for
STEMI [mean baseline LV ejection fraction - 47 plus or minus 7%, increased to
55 plus or minus 9% similarly in both groups (p = 0.001)]. In the trial, 97%
of patients underwent stenting. Thrombolysis In Myocardial Infarction (TIMI)
grade flow (a secondary endpoint) was 0 in approximately 80% of patients prior
to the procedure. After the procedure, final TIMI 3 grade flow was achieved
in 88% of tirofiban patients vs. 86% of abciximab patients, respectively
(p = 1.0).
Investigators conclude that abciximab and tirofiban affected both initial
angiographic outcomes and 30-day recovery of LV function following primary
coronary angioplasty. With no major bleeding or severe thrombocytopenia and
no need for red blood cell transfusions, researchers say the study provides
important information about the safety of high-dose bolus tirofiban. More
abciximab-treated patients than tirofiban-treated patients [8% vs. 4%,
respectively] experienced minor bleeding, but this difference was not
significant (p=0.71). The 30-day incidence of major adverse cardiovascular
events was also greater, but not significantly so, in the abciximab group when
compared to the tirofiban group [6% vs. 4% (p = 0.74)].
Eric Topol, M.D. of the Cleveland Clinic Heart Center explains, "This
study provides further support for doing a repeat large-scale trial testing
tirofiban versus abciximab, since so much data now suggest the bolus dose we
used (for tirofiban) in TARGET was inappropriately low." In the Do Tirofiban
and ReoPro Give Similar Efficacy Outcomes Trial (TARGET) trial, tirofiban
was given at 10 mcg/kg bolus followed by a 0.15 mcg/kg/min infusion for 18 to
24 hours.

Important Information About AGGRASTAT(R) Injection
AGGRASTAT(R) was approved by the Food and Drug Administration (FDA) on
May 14, 1998. AGGRASTAT(R), in combination with heparin, and aspirin, if not
contraindicated, is indicated for the treatment of ACS including patients who
are to be managed medically and those undergoing PTCA or atherectomy. In this
setting, AGGRASTAT(R), has been shown to decrease the rate of a combined
endpoint of death, new myocardial infarction or refractory ischemia/repeat
cardiac procedure. In most patients, AGGRASTAT(R) should be administered
intravenously, at an initial rate of 0.4 mcg/kg/min for 30 minutes and then
continued at 0.1 mcg/kg/min. For complete information, please refer to the
product's prescribing information.
AGGRASTAT(R) (tirofiban hydrochloride) is contraindicated in patients with
known hypersensitivity to any component of the product; active internal
bleeding or a history of bleeding diathesis within the previous 30 days; or a
history of intracranial hemorrhage, intracranial neoplasm, arteriovenous
malformation, or aneurysm. Other contraindications to AGGRASTAT(R) include: a
history of thrombocytopenia following prior exposure to AGGRASTAT(R); history
of stroke within 30 days or any history of hemorrhagic stroke; major surgical
procedure or severe physical trauma within the previous month; or history,
symptoms, or findings suggestive of aortic dissection. AGGRASTAT(R) is
also contraindicated in patients with: severe hypertension (systolic blood
pressure >180 mmHg and/or diastolic blood pressure >110 mmHg); concomitant use
of another parenteral GP IIb/IIIa inhibitor; or acute pericarditis.
Bleeding is the most common complication encountered during therapy with
AGGRASTAT(R). Administration of AGGRASTAT(R) is associated with an increase
in bleeding events classified as both major and minor bleeding events, by
criteria developed by the Thrombolysis In Myocardial Infarction Study group
(TIMI). Most major bleeding associated with AGGRASTAT(R) occurs at the
arterial access site for cardiac catheterization. Fatal bleedings have been
reported. AGGRASTAT(R) should be used with caution in patients with platelet
count <150,000/mm3, in patients with hemorrhagic retinopathy, and in chronic
hemodialysis patients. Because AGGRASTAT(R) inhibits platelet aggregation,
caution should be employed when it is used with other drugs that affect
hemostasis. The safety of AGGRASTAT(R) when used in combination with
thrombolytic agents has not been established. During therapy with
AGGRASTAT(R), patients should be monitored for potential bleeding. When
bleeding cannot be controlled with pressure, infusion of AGGRASTAT(R) and
heparin should be discontinued.
The following additional adverse reactions have been reported in post-
marketing experience: Bleeding: intracranial bleeding, retroperitoneal
bleeding, hemopericardium, and pulmonary (alveolar) hemorrhage. Fatal
bleedings have been reported; Body as a whole: acute and/or severe decreases
in platelet counts which may be associated with chills, low grade fever, or
bleeding complications; Hypersensitivity: rash and/or hives.

Medicure Inc.: Positive AGGRASTAT(R) Results Featured in the Journal of the American College of Cardiology
PROTOCOL FOR NEW AGGRASTAT(R) STUDY IN AMERICAN HEART JOURNAL
WINNIPEG, MANITOBA--(Marketwire - July 11, 2007) - Medicure Inc. (TSX:MPH)(AMEX:MCU), a cardiovascular focused, biopharmaceutical company, today announced that the two-year, follow-up results from the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare Metal Stent In Acute Myocardial Infarction) study were published in the July edition of the Journal of the American College of Cardiology (JACC).

The article, titled, "Two-Year Clinical Follow-Up After Sirolimus-Eluting Versus Bare-Metal Stent Implantation Assisted by Systematic Glycoprotein IIb/IIIa Inhibitor Infusion in Patients With Myocardial Infarction", outlines the potential benefit of AGGRASTAT® (tirofiban hydrochloride) plus sirolimus-eluting stent (SES) versus Reopro® (abciximab) plus bare-metal stent (BMS) in the prevention of the cumulative incidence of death, myocardial infarction (MI), or target vessel revascularization (TVR) in acute myocardial infarction patients after two years.

At two years, the cumulative incidence of death, MI, or TVR was lower in the AGGRASTAT®-SES group compared with the Reopro®-BMS group (24.2% vs. 38.6%, p equals 0.038). This statistically significant outcome at two years is similar to the previously reported eight month results that were published in The Journal of the American Medical Association (May 2005).

The positive results from STRATEGY were the impetus for an ongoing larger factorial design study titled MULTI-STRATEGY (Multicentre Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab and Sirolimus-Eluting Stent Versus Base Metal Stent in Acute Myocardial Infarction). The MULTI-STRATEGY protocol was published in the July edition of the American Heart Journal.

This 600-patient study will further assess AGGRASTAT®-SES versus Reopro®-BMS in the prevention of the cumulative incidence of death, MI, and TVR in acute myocardial infarction patients. The results from MULTI-STRATEGY are anticipated to be presented at a prominent scientific symposium in early 2008.

"These papers highlight the ongoing interest in evaluating new investigational uses of AGGRASTAT® in the treatment of high risk cardiovascular disease patients," stated Medicure's President and CEO, Albert D. Friesen, PhD. "We believe AGGRASTAT® has significant untapped potential, and look forward to the presentation of new data from studies such as MULTI-STRATEGY in the coming year."

Medicure acquired the exclusive U.S. rights to AGGRASTAT®, in August 2006.

Important Information About AGGRASTAT®

AGGRASTAT® was approved by the Food and Drug Administration on May 14, 1998.

AGGRASTAT®, in combination with heparin, is indicated for the treatment of acute coronary syndrome, including patients who are to be medically managed and those undergoing percutaneous transluminal coronary angioplasty (PTCA) or atherectomy. In this setting AGGRASTAT® has been shown to decrease the rate of a combined endpoint of death, new myocardial infarction or refractory ischemia/repeat cardiac procedure. AGGRASTAT® has been studied in a setting that included aspirin and heparin.

AGGRASTAT® is contraindicated in patients with known hypersensitivity to any component of the product; active internal bleeding or a history of bleeding diathesis within the previous 30 days; or a history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm. Other contraindications to AGGRASTAT® include: a history of thrombocytopenia following prior exposure to AGGRASTAT®; history of stroke within 30 days or any history of hemorrhagic stroke; major surgical procedure or severe physical trauma within the previous month; history, symptoms, or findings suggestive of aortic dissection. AGGRASTAT® is also contraindicated in patients with: severe hypertension (systolic blood pressure greater than 180 mmHg and/or diastolic blood pressure greater than 110 mmHg); concomitant use of another parenteral GP IIb/IIIa inhibitor; or acute pericarditis.

Bleeding is the most common complication encountered during therapy with AGGRASTAT®. Administration of AGGRASTAT® is associated with an increase in bleeding events classified as both major and minor bleeding events, by criteria developed by the Thrombolysis in Myocardial Infarction Study group (TIMI). Most major bleeding associated with AGGRASTAT® occurs at the arterial access site for cardiac catherterization. Fatal bleedings have been reported. AGGRASTAT® should be used with caution in patients with platelet count less than 150,000/mm3, in patients with hemorrhagic retinopathy and in patients in chronic hemodialysis. Because AGGRASTAT® inhibits platelet aggregation, caution should be employed when it is used with other drugs that affect hemostasis. The safety of AGGRASTAT® when used in combination with thrombolytic agents has not been established. During therapy with AGGRASTAT®, patients should be monitored for potential bleeding. When bleeding cannot be controlled with pressure, infusion of AGGRASTAT® and heparin should be discontinued.

About Medicure Inc.

Medicure is a biopharmaceutical company focused on the research, development and commercialization of novel compounds to treat cardiovascular disorders. The Company's solid position in this field is highlighted by the following:

- Lead compound MC-1 in pivotal Phase 3 study for FDA approval

- Four positive Phase 2 trials completed with MC-1

- FDA Fast Track designation for MC-1

- U.S. rights to AGGRASTAT® Injection (tirofiban hydrochloride)

- Combination of MC-1 and lisinopril (MC-4232) completed Phase 2

- Dual action antithrombotic, MC-45308, with positive preclinical results

Medicure also has a medicinal chemistry based Drug Discovery program focused on discovery and advancement of novel small molecule anti-ischemics and antithrombotics towards human clinical studies.

This press release contains forward-looking statements, as defined under applicable securities legislation, that involve risks, which may cause actual results to differ materially from the statements made, and accordingly may be deemed to be forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The forward-looking statements are made as of the date hereof, and the Company disclaims any intention and has no obligation or responsibility to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise except as required by law. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, events or developments to be materially different from any future results, events or developments expressed or implied by such forward-looking statements. Such factors include, among others, the Company's stage of development, lack of product revenues, additional capital requirements, risks associated with the completion of clinical trials and obtaining regulatory approval to market the Company's products, the ability to protect its intellectual property, dependence on collaborative partners and the ability to meet its debt obligations. These factors should be considered carefully and readers are cautioned not to place undue reliance on such forward-looking statements. Additional risks and uncertainties relating to the Company and its business can be found in the "Risk Factors" section of its Form 20F for the year ended May 31, 2006.


For more information, please contact

Medicure Inc.
Derek Reimer
Chief Financial Officer
1-888-435-2220
(204) 488-9823 (FAX)

or

Medicure Inc.
Adam Peeler
Manager of Investor & Public Relations
1-888-435-2220
(204) 488-9823 (FAX)
Email: info@medicure.com
Website: www.medicure.com

A N A L I T I K A Focus on Healthcare Medicure Inc. (MCU)
Biotechnology
Quote: $1.35 // Price Target: $6.00 (+344%)
Research Alert
Erik Danielsen
July 10th, 2007

e.danielsen@analitika.com

this was posted by balistic 117 on the yahoo message board

w w w . a n a l i t i k a . c o m

MARKET DATA

Mkt. Cap.: $157.0MM
Enterprise Value: $134.M
52Wk Hi-Low: $1.70 -$0.91
Outst. Shares: 116.26M
Fully Dil. Shares: 131.0M
Float: 105.3M
Daily Volume: 109,000
Short Position: n/a
VARIOUS METRICS
Cash : $43.4M
Cash Burn ‘07: $27.0M
LTD (MM): $11.5M
Short Position: 107,000
Insider buying: None
Insider Ownership: ~10%
Institutional
holdings: 24%
EARNINGS DATA
FY – 05/31 2006 2007E 2008E
Q1 (0.06) (0.03) (0.06)
Q2 (0.05) (0.06) (0.04)
Q3 (0.04) (0.08) (0.04)
Q4 (0.03) (0.08)E (0.04)
FY EPS (0.17) (0.17)E (0.09)
Revenue 0.3M 9.5M 20.0
VALUATION METRICS
FY – 12/31 2006 2007E 2008E
P/E NM NM NM
PEG NM NM NM
Sales Mult. NM NM NM

Medicure’s shares have continued to trend downwards since the shares set a high in February 2006, which, in our view, is in sharp contrast to the underlying fundamentals at the company. The company has implemented its business plan, reported highly positive
clinical data for both of its lead compounds and thereby built significant tangible share-holder value. Consequently, we strongly encourage investors to take advantage of the current price weakness and either build or add to their positions.

Key Investment Considerations:

•Strong Management: Medicure has a strong, proven management team that consis-tently delivers on all major corporate milestones.

•Late-Stage Product Candidates: Medicure clearly has one of the clinically most ad-vanced cardiovascular product pipelines of any biotech companies in our 900+ companies database. The company’s lead product, MC-1, is being developed as a cardioprotective agent and entered a 3000 patient Phase III registration study in December 2006. Top-line results are expected by the end of Q1-2008 and the product could be on the market by H1-2009. Medicure’s second product candidate, MC-4232 for diabetics with concomitant hypertension, has successfully concluded Phase IIb clinical testing and is now ready to enter pivotal Phase III clinical testing. These two products alone have by our estimate a combined market potential in excess of $1.5BN in the U.S. alone. Currently, Medicure own 100% worldwide rights to its product candidates.

•Near-Term Growth Opportunity: The August 2006 acquisition of Aggrastat, an FDA approved platelet aggregation inhibitor used to treat acute coronary syndromes, has catapulted the company into an exclusive, small group of biotech companies with significant near-term, sales-growth potential. Aggrastat was re-launched in the United States in late October 2006 with a 15 person dedicated sales-force. At the time of launch, Aggrastat generated ~$8M in annualized revenues equivalent to less than a 2% market share of a an estimated $450M annual market in the U.S. Aggrastat had not been actively marketed in the U.S. for some 3-4 years. By contrast, in Europe, where the product has been marketed actively in recent years, Aggrastat is the market leader of the three competing products in the therapeutic class with an estimated 35% market share. Aggrastat is not only a near-term, sales-growth opportunity, but importantly, it also allows the company to build and train a sales-force in anticipation of the approval of MC-1.

•Additional Licensing Opportunities Could Provide Near-Term Upside: We believe there is an excellent probability that the company will be announcing additional commercial initiatives over the next year that would be immediately incremental to
its revenue base. We look for either additional co-promotion and/or out-right product licensing agreements. •Significantly Undervalued: At current valuation levels, we believe Medicure’s common stock is significantly undervalued. We expect the stock to appreciate sharply in value, as the company continues to execute its business plan that we expect will result
in a strong news-flow over the next 9 months. We believe Medicure’s stock should be valued at $600-$900M today, implying a 12-18 months price target of $6-9.

Medicure Is Grossly Undervalued Relative To Other Small Cap Biotech Companies

We strongly believe that Medicure, at current valuation levels of ~US$157M (and enterprise value of less than $134M), continues to represent an extraordinary investment opportunity. The company is significantly undervalued by any valuation parameter that we use. In particular, Medicure is trading at an unjustified discount to a group of cardiovascular biotech companies, as highlighted by the table:

Company Ticker Quote Mkt Cap
Alexion Pharma ALXN $47.95 $1.774,0M
Cardiome CRME $9.20 $581.0M
CV Therapeutics CVTX $12.57 $746.2M
Average: $1.033,8
Median: $746.0
Medicure MCU $1.35 $157,0
Discount to median: 79%

We actually believe that Medicure’s commercial potential is much larger than any of the companies indicated in the table above. Furthermore, we have reviewed, not only the companies highlighted in the table, but also a number of other biotech companies in our database, in particular
with regard to:

• Management’s track record of delivering on corporate milestones in a timely fashion.

• Near-term sales-growth potential.
• Breadth, depth and clinically advanced stage of product pipeline.

• Long-term market potential of late-stage product pipeline.

• Anticipated news flow over the next 12 months.

* Current market cap in relation to the above parameters.

Based on our review, we feel very comfortable stating that Medicure ranks among the most attractively valued companies for all of the parameters reviewed. As the table above indicates, the company trades at a 79% discount to companies we feel are comparable, but at the same time have weaker fundamentals. One of the companies highlighted above is Alexion. Alexion once enjoyed a market cap of approximately $1Bn prior to reporting disappointing Phase III results for its heart-protective agent, Pexelizumab. Pexelizumab was being developed basically for the same indications Medicure is pursuing with MC-1. We mention this because we believe Alexion’s valuation at the time based entirely on the prospects of Pexelizumab.

However, in the meantime, Alexion gained FDA approval for another of its product candidates, Soliris, for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), which one leading Wall Street analyst recently estimated has a peak sales potential of approximately $400M annually. This is virtually the same as Medicure’s Aggrastat’s market opportunity in the U.S. Alexion’s market cap has despite the disappointment with Pexelizumab soared from $1Bn to $1.77Bn based on the prospects of Soliris. Considering that Medicure in addition to Aggrastat has two products with blockbuster sales potential in late-stage clinical development, and that MC-1 could reach the market within the next 18 months, we conclude that Medicure must be grossly undervalued.

Medicure is currently enjoying a market cap equivalent to about 8.8% (!) of Alexion’s current market cap
Medicure Consistently Delivers Tangible Value To Shareholders

Medicure has had an impressive news flow over the past twenty four months; including the publication of two highly successful phase IIb clinical trials for MC-1 and MC-4232 and, most recently, the acquisition of Aggrastat, which we estimate has the potential to grow at least 5 times over the next 2-3 years. Aggrastat was purchased at a very reasonable price of roughly 2x its trailing twelve
months revenues.

Since Alexion’s Pexulizumab failed to show efficacy in Phase III as a cardio-protective agent, Medicure has now emerged as the leader in the field. This statement is shared by leading clinical investigators we have spoken to at the most prestigious hospitals in the U.S.

We Expect A Strong News Flow Through 2008

The next 12 months will be extremely exiting to Medicure’s shareholders as we expect the company to report top-line date from its confirmatory Phase III trial for MC-1 in CABG in early 2008. This will clearly be a crucial time in the company’s history. We believe the probability of success in the MC-1 Phase III trial is high and thus a significant revaluation of the stock is likely to occur at the latest by the end of Q1-2008.

The following table summarizes some of the value-driving events we expect to occur over the next 18 months.

Milestone Event Timing

~ Completion of patient enrollment in confirmatory Phase III trial for MC-1 in CABG Oct-2007
~ In-licensing of new commercial products H1-2008
~ Report accelerating sales growth of Aggrastat Dec-2007
~ Report Top-Line Results from MC-1 Phase III Trial Q1-2008
~ File NDA for MC-1 H1-2008
~ FDA Clearance and launch of MC-1 End-2008
~ Announce corporate partner for MC-1 H1-2008

Conclusion

We believe Medicure is significantly undervalued at current valuation levels. We believe Medicure is a “quality small-cap biotech stock” that has a broad product portfolio and a proven management team, lead by Dr. Albert Friesen. Consequently, we strongly recommend growth-oriented investors, familiar with inherent risks of investing in biotech companies, to either add to or take
new positions in Medicure at current price levels.

For more information: www.analitika.com

The author is compensated by Medicure through a consulting agreement for his business develpment services.

ANALITI KA Identifying Investment Opportunities In Healthcare

Rate it:

http://www.investorshub.com/boards/board.asp?board_id=5336

rodman and renshaw webcast medicure

http://www.wsw.com/webcast/rrshq11/mcu/

Medicure Announces MC-1 Symposium at American Association for Thoracic Surgery Meeting
Thursday May 3, 8:00 am ET


WINNIPEG, MANITOBA--(MARKET WIRE)--May 3, 2007 -- Medicure Inc. (Toronto:MPH.TO - News)(AMEX:MCU - News), a cardiovascular focused biopharmaceutical company, today announced it is providing an educational grant to support an accredited satellite symposium during The American Association for Thoracic Surgery's 87th Annual Meeting in Washington, D.C. The symposium will highlight Medicure's lead clinical product MC-1's potential role in the treatment of coronary artery bypass graft (CABG) surgery patients.
ADVERTISEMENT


The symposium, titled "Novel Cardioprotective Treatment for Coronary Artery Bypass Graft", is scheduled for Monday, May 7, 2007, at 6 p.m. Eastern at the Renaissance Washington Hotel in the Renaissance Ballroom West. The symposium has been assessed by the Accreditation Council for Continuing Medical Education and awarded accreditation as a provider of continuing medical education for physicians.

Symposium panel members will include Dr. Michel Carrier, Director of Cardiovascular Surgery Program at the Montreal Heart Institute and a Principal Investigator for the MEND-CABG II trial. Also on the panel are MEND-CABG II steering committee members Dr. John H. Alexander, Associate Professor of Medicine in the Division of Cardiovascular Medicine at Duke Clinical Research Institute, and Dr. Robert W. Emery, Jr., Chief of Cardiac Surgery at St. Joseph's Hospital, in St. Paul, Minnesota.

"This symposium is the ideal setting to update the thoracic surgery community on the clinical development of MC-1," stated Dr. Alexander. "If the ongoing Phase 3 MEND-CABG II study delivers similar data to the previous Phase 2 study, MC-1 could represent a major and easy-to-implement advance in the treatment of patients undergoing CABG and perhaps other major cardiac surgery. I look forward to sharing my enthusiasm for the MC-1 clinical development program with the thoracic surgery community."

The American Association for Thoracic Surgery (AATS) was founded in 1917. Its annual meeting brings together almost 3,000 of the most prominent specialists from around the world to address cutting-edge modalities of therapy for cardiothoracic diseases.

About MC-1

MC-1 is a novel cardioprotective compound that is being evaluated in the prevention of cardiac damage. Medicure has completed two Phase 2 studies with MC-1 demonstrating its cardioprotective effects. MC-1 has received a Fast Track Designation from the FDA as a treatment to reduce cardiovascular events associated with ischemic and/or ischemic reperfusion injury in patients experiencing percutaneous coronary interventions, coronary artery bypass graft surgery and acute coronary syndrome (ACS). Medicure intends to develop MC-1 for the CABG surgery and ACS markets, which have a combined annual incidence of approximately two million in the United States.

About MEND-CABG II

The Phase 3 MEND-CABG II is a double-blind, randomized, placebo-controlled clinical trial that will enroll up to 3,000 patients undergoing CABG surgery at approximately 120 cardiac surgical centers throughout North America and Europe. Study patients will be randomized to receive placebo or MC-1 250 mg prior to surgery and for 30 days post operatively (POD 30). The primary efficacy endpoint of MEND-CABG II is the reduction in the composite of cardiovascular death and non-fatal myocardial infarction up to POD 30. Study patients will be followed for 60 days after treatment (90 days post operatively) for additional safety and efficacy analysis. Study enrollment was initiated in November 2006.

The study protocol and entry criteria for MEND-CABG II closely follow that of the Phase 2 MEND-CABG study. MEND-CABG was a Phase 2 study involving 901 patients that evaluated MC-1 versus placebo in patients undergoing CABG surgery. The 250 mg dose of MC-1 had a 37.2% reduction in the composite of cardiovascular death, non-fatal myocardial infarction (peak CK-MB greater than or equal to 100ng/ml), and non-fatal stroke versus placebo (p equals 0.028). The reduction in the composite endpoint was driven by a significant 46.9% decrease in the incidence of non-fatal myocardial infarction (peak CK-MB equals 100ng/ml) with the 250 mg dose of MC-1 versus placebo (p equals 0.008). The clinical results reported at POD 30 were maintained throughout the 90 day follow up period (POD 90). Safety analysis included in the MEND-CABG study demonstrated MC-1 was safe and well tolerated. The incidence of adverse events in the study was comparable across both treatment and control groups.

In addition to the MEND-CABG study, the 60 patient MEND-1 study demonstrated that MC-1 had a statistically significant reduction in the cardiac enzyme CK-MB in patients undergoing percutaneous coronary intervention (PCI).

About Medicure Inc.

Medicure is a biopharmaceutical company focused on the research, development and commercialization of novel compounds to treat cardiovascular disorders. The Company's solid position in this field is highlighted by the following:

- Lead compound MC-1 in pivotal Phase 3 study for FDA approval

- Four positive Phase 2 trials completed with MC-1

- FDA Fast Track designation for MC-1

- U.S. rights to AGGRASTAT® Injection (tirofiban hydrochloride)

- Combination of MC-1 and lisinopril (MC-4232) completed Phase 2

- Dual action antithrombotic, MC-45308, with positive preclinical results

Medicure also has a medicinal chemistry based Drug Discovery program focused on discovery and advancement of novel small molecule anti-ischemics and antithrombotics towards human clinical studies.

Medicure to Present at Deutsche Bank's Annual Health Care Conference
Tuesday May 1, 9:00 am ET


WINNIPEG, MANITOBA--(MARKET WIRE)--May 1, 2007 -- Medicure Inc. (Toronto:MPH.TO - News)(AMEX:MCU - News), a cardiovascular focused biopharmaceutical company, today announced its President and CEO, Albert D. Friesen, PhD, will deliver a corporate presentation at Deutsche Bank's 32nd Annual Health Care Conference at 4 p.m. Eastern on Wednesday May 2, 2007 in the Chinese Room of The Mayflower Hotel in Washington, D.C. The presentation will be made available by webcast and can be accessed on the Investor Relations page of the Medicure website at www.medicure.com.
ADVERTISEMENT


About Medicure Inc.

Medicure is a biopharmaceutical company focused on the research, development and commercialization of novel compounds to treat cardiovascular disorders. The Company's solid position in this field is highlighted by the following:

- Two drugs, MC-1 & MC-4232, in late stage clinical development

- Four positive Phase II trials completed with MC-1

- FDA Fast Track designation for MC-1

- U.S. rights to AGGRASTAT® Injection (tirofiban hydrochloride)

- Dual action antithrombotic, MC-45308, with positive preclinical results

Medicure also has a medicinal chemistry based Drug Discovery program focused on discovery and advancement of novel small molecule anti-ischemics and antithrombotics towards human clinical studies.

Noble Financial Analyst report

I hadn't heard of the firm but it is an excellent report. Better than Merriman's

BUY MCU: Aggrastat’s rebirth + MC-1’s potential = likely upside before Mar-08 data
Analyst: Laurence S. Bleicher
303-257-3263
lbleicher@noblefinancialgroup.com
US$1.87
US$0.91
US$144.2M
US$122.0M
116.3M
105.4M
24.2%
294K
126K
MC-1 PHASE 2 DATA SUGGEST A RELATIVELY LOW-RISK PHASE 3 TRIAL
We believe the current Phase 3 CABG surgery trial of MC-1 will
succeed, as it is much better statistically powered than a Phase 2b trial
that yielded statistically and clinically significant results
MC-1 HAS SIGNIFICANT POTENTIAL BEYOND CABG ALONE & IN COMBINATION
Phase 2 trials have shown positive MC-1 data in PCI, positive ace-inhibitor/
MC-1 combination data in diabetic hypertension
AGGRASTAT A NEAR-TERM SLEEPER FOR MCU
Early efforts to recapture market share are meeting with success; if
nothing else Aggrastat keeps a future MC-1 salesforce productive
2007 US$3 PRICE TARGET ATTAINABLE BEFORE MARCH-08 BINARY EVENT
MCU is significantly undervalued despite MC-1’s stage of
development given its potential; applying a 30x multiple to our Nov-2012
estimate or a 25x multiple to our Nov-2013 estimate and
discounting by 40% for four or five
years, respectively, yields a 2007
price target of US$3, attainable
before pivotal MC-1 data in
March-08
Revenue (US$millions)
F2007E F2008E F2009E
Aug US$0.2 US$3.0 US$4.3
Nov US$1.3 US$3.4 US$4.6
Feb US$2.2 US$3.7 US$4.9
May US$2.7 US$4.0 US$5.1
FY US$6.4 US$14.1 US$18.9
Earnings (per share, US$)
(future q’s omit amortization, forex gains)
F2007E F2008E F2009E
Aug US$(0.03) US$(0.11) US$(0.06)
Nov US$(0.06) US$(0.11) US$(0.06)
Feb US$(0.07) US$(0.12) US$(0.07)
May US$(0.11) US$(0.06) US$(0.07)
FY US$(0.27) US$(0.40) US$(0.26)
P/E n/a n/a n/a
Five-Year EPS Growth n/a
EV/EBITDA (ttm) n/a
ROE (ttm) n/a
Debt/Cap (mrq) n/a
Div./Div. Yield n/a
Fiscal Year May-31
Refer to pages #16-17 for Disclosures
Throughout 2007 add’l MC-1 &
Aggrastat data publications
November-07 finish enrolling
pivotal MC-1 CABG trial
Interim DSMB look at pivotal
MC-1 CABG trial
March-08 pivotal MC-1 CABG
trial data
US$3
04/24/07
Biotechnology & Specialty Pharmaceuticals
M
2
Medicure, Inc. (MCU - US$1.24) 04/24/07
Medicure, Inc. (MCU) is a commercial-stage and research
and development-stage pharmaceuticals company. At
this time, MCU’s commercial portfolio consists of
Aggrastat, a GP IIb/IIIa inhibitor for use in Acute
Coronary Syndrome. MCU’s most advanced pipeline
product is MC-1, an unpartnered, highly novel agent, in
Phase 3 for use in Coronary Artery Bypass Graft surgery.
MCU’s pipeline includes several other unpartnered
cardiovascular compounds, both chronic and acute, from
pre-clinical to pre-Phase 3.
We believe that the current Phase 3 CABG surgery trial
of MC-1 will be successful, as that study is much better
statistically powered than a Phase 2b trial that yielded
statistically and clinically significant results. MCU has a
Special Protocol Assessment from the FDA for the
current Phase 3 CABG surgery trial of MC-1. Pivotal
data are expected in March of 2008; an interim Data
Safety Monitoring Board look will occur before that.
Also, we believe that MCU’s early success in its initial
efforts to increase the market share of its recently
acquired product, Aggrastat, will continue. Finally, we
are optimistic about the rest of MCU’s pipeline, to which
we assign no value at this time to be conservative.
Price Target
Our US$3 2007 price target is an average of two 2007
price targets. We apply a 30x multiple to our Nov-2012
estimate and discount by 40% for four years to attain a
2007 price target of US$3.20; we apply a 25x multiple to
our Nov-2013 estimate and discount by 40% for five
years to attain a 2007 price target of US$2.90. (If we
were to model flat Aggrastat market share going forward,
our new 2007 price target would still imply
approximately 100% upside. If the Phase 3 CABG
surgery trial of MC-1 were to be successful, we would
lower our discount rate to the low-20s, which would raise
the 2007 present value of what would then be our 2008
price target to between US$5 and US$6, not including
whatever value might have emerged in the meantime
from the pipeline.).
A survey of seven US and Canadian analysts reveals an
average rating closer to Buy than Hold. Over the last
month, this average rating has not changed. The mean
price target among these analysts is US$2.69, with a price
target range from US$2 to US$3.34.
2
Medicure, Inc. (MCU) is a commercial and R&D-stage pharmaceuticals company. At this time, MCU s commercial portfolio consists of Aggrastat, a GP IIb/IIIa
inhibitor for use in Acute Coronary Syndrome. MCU s most advanced pipeline product is MC-1, an unpartnered, highly novel agent, in Phase 3 for use in
Coronary Artery Bypass Graft surgery, and in pre-Phase 3 and earlier stages of clinical development for other acute cardiovascular indications. MCU s pipeline
includes several other unpartnered cardiovascular compounds, both chronic and acute, at various stages of development, from pre-clinical to pre-Phase 3.

3
Medicure, Inc. (MCU - US$1.24) 04/24/07
Overview
Medicure, Inc. (MCU) is a commercial-stage and research
and development-stage pharmaceuticals company. At
this time, MCU’s commercial portfolio consists of
Aggrastat, a GP IIb/IIIa inhibitor for use in Acute
Coronary Syndrome (ACS), for which MCU obtained US
rights from MGI Pharmaceuticals (MOGN, Not Rated) in
August of 2006. MCU’s most advanced pipeline product
is MC-1, an unpartnered, highly novel agent, in Phase 3
for use in Coronary Artery Bypass Graft (CABG)
surgery, and in pre-Phase 3 and earlier stages of clinical
development for other acute cardiovascular indications.
MCU’s pipeline includes several other unpartnered
cardiovascular compounds, both chronic and acute, at
various stages of development, from pre-clinical to pre-Phase
3, of which some are combinations of MC-1 with
other agents while others are not based on MC-1.
Aggrastat for ACS
MCU currently commercializes Aggrastat in the US.
Aggrastat is the only small-molecule therapy among the
GP IIb/IIIa inhibitors, a class of antiplatelet agents for use
in ACS that also includes Integrilin from Schering-Plough
(SGP, Not Rated) and ReoPro from Eli Lilly
(LLY, not rated). Aggrastat enjoys a pricing advantage
vs. these harder-to-manufacture large molecule agents.
While the GP IIb/IIIa class saw its penetration of the ACS
market decline for several years, that penetration appears
to have stabilized in the low-20s over the last few
quarters; MCU’s acquisition of US Aggrastat rights
appears therefore to have been very well-timed.
Similarly, while Aggrastat’s share of the GP IIb/IIIa class
fell for several years, that share has increased markedly
over the last few quarters—MCU’s initial efforts to
promote the agent appear to have met with success thus
far, having likely been bolstered by the presentation of
data suggesting Aggrastat’s non-inferiority vs. ReoPro at
the 2006 American Heart Association meeting shortly
after MCU acquired US Aggrastat rights. MCU owes
Merck (MRK, Not Rated) at least a 5% royalty on US
Aggrastat sales.
MCU is initially developing its lead drug candidate, an
orally available, small-molecule, P2 purinergic (P2x)
receptor antagonist called MC-1, in three different acute
cardiovascular indications. MCU was founded to in-license
the worldwide rights to MC-1, which had been
discovered at the University of Manitoba. MC-1 is
unpartnered at this time, although MRK has acquired the
ex-North America right of first refusal for any
combination of Aggrastat and MC-1. MRK negotiated
this option in the course of MRK’s approval of MOGN’s
sale to MCU of US rights for Aggrastat; MRK had
retained the right to review and ultimately authorize any
Aggrastat transaction made by MOGN.
We believe that our sales assumptions for Aggrastat in
ACS and MC-1 in CABG surgery, to be detailed below,
are conservative. For Aggrastat, we assume that the GP
IIb/IIIa class will maintain its current, stable penetration
of the ACS market. We assume that Aggrastat will very
gradually increase its share of the GP IIb/IIIa class,
reaching only 17% volume-share in mid-2013, its seventh
full year of active detail by the MCU salesforce. We feel
this is conservative, as Aggrastat is the class leader in
Europe, and held 17% volume-share in the US as recently
as 2003. Additionally, our due diligence suggests that
Aggrastat arguably has not in several years, if ever, been
as high a priority for any US salesforce as it is now for
MCU’s; and, that Aggrastat appears to offer at least
equivalent efficacy to its competitors at a lower price.
MC-1 CABG surgery indication
MC-1’s most advanced indication is CABG surgery, for
which the agent is currently in a Phase 3 trial under a
Special Protocol Assessment (SPA): a non-binding
agreement with the FDA that the trial, if successfully
completed, will, in combination with other, previously
attained data, form an adequate basis for a New Drug
Application (NDA). MCU began enrolling this 3,000-
patient Phase 3 trial of MC-1 in November of 2006, and
targets enrollment completion in November of 2007, data
release in March of 2008 (an earlier, interim Data Safety
Monitoring Board (DSMB) examination of the data is
scheduled), and MC-1 NDA submission for CABG
surgery in June of 2008. The trial generally replicates the
protocol of a successfully completed, randomized,
placebo-controlled, double-blind, dose-ranging 900-patient
Phase 2b trial in CABG surgery. In that trial, the
regimen of MC-1 currently being pursued in Phase 3
(250mg pre/post-op, then once daily for 30 days)
demonstrated a statistically significant 37% reduction in a
composite of cardiovascular-related death, non-fatal
myocardial infarction (MI), and non-fatal stroke at post-operative
day 30 vs. placebo (p-value less than 0.03);
maintained a statistically significant reduction of similar
size in that composite vs. placebo throughout a follow-up
period out to post-op day 90; and displayed an equivalent
adverse event profile vs. placebo.

4
Medicure, Inc. (MCU - US$1.24) 04/24/07
Our due diligence has determined that the results attained
in the Phase 2b CABG surgery trial of MC-1 suggest that
MCU had probably substantially underestimated the
actual effect size of the agent in planning that trial, thus
overpowering it. The Phase 3 CABG trial nonetheless
assumes the same MC-1 effect size, and is probably
therefore better powered than its ostensible 85% power to
detect a 20% reduction in the composite endpoint.
Regardless, the Phase 3 trial is much better powered than
the successful Phase 2b trial, due to its size among other
reasons; as such, we believe that the current Phase 3
CABG surgery trial of MC-1 will be successful.
We believe that after completing this trial, MCU will
attain a commercial partner for MC-1 outside the US, but
will retain US rights to the drug and market it through its
existing US Aggrastat salesforce. With US$22M of net
cash, MCU has sufficient resources to conclude this trial.
Based upon MCU’s aforementioned target of a June of
2008 NDA filing of MC-1 for CABG surgery, we expect
MCU will launch MC-1 in the US in mid-2009, and
MCU’s partner will launch MC-1 ex-US one year later.
As MCU has received fast-track designation for MC-1 in
CABG surgery (as well as in other indications), the NDA
might receive expedited review; accordingly, we feel our
expectation of a mid-09 US launch of MC-1 is
conservative.
For MC-1, we assume that the agent will garner slightly
less than a one-half penetration/share of the US CABG
surgery market in mid-2014, after five full years on the
market; we model half that trajectory for the EU market,
beginning one year later as previously discussed. We
believe this assumption would be highly conservative if
MC-1 were to succeed in its current Phase 3 trial, as it
would then offer a unique mechanism by which to reduce
death and/or MI in CABG surgery patients. We further
assume that the price of a course of MC-1 therapy will be
set initially at only US$600 per course of therapy, about
25% above the price of a course of Aggrastat therapy
(despite the latter being 60-75% cheaper than the other
GP IIb/IIIa inhibitors), and will undergo minimal price
increases. We feel that this assumption too would be
highly conservative if MC-1 were to succeed in its current
Phase 3 trial.
MCU’s other unpartnered pipeline products
Besides MC-1 for CABG surgery, MCU also possesses
an unpartnered pipeline of other MC-1 indications and of
other agents, from pre-clinical to pre-Phase 3, addressing
both acute and chronic markets. MC-1 has received fast-track
designation for not only CABG surgery, but also for
ACS and for angioplasty, also known as Percutaneous
Coronary Intervention (PCI). MCU has successfully
completed a Phase 2a trial of MC-1 in PCI; however, as
this was only a biomarker-endpoint trial, and MCU
intends to pursue MC-1 in Phase 3 next in ACS
(admittedly a closely related indication to PCI), we assign
no value to MC-1 in ACS or PCI at this time for the sake
of conservatism. This is probably excessively
conservative, as the biomarker measured in this trial is
known to be correlated strongly with meaningful clinical
events. MCU is also investigating MC-1 in a Phase 1
trial in stroke, which at this time is omitted from
valuation due to the lack of Phase 2 data thus far.
Two combination products of MC-1 with other agents are
currently in clinical-stage testing. MC-4232 is a
combination of MC-1 and the ACE-inhibitor, lisinopril,
for which MCU is finalizing a Phase 3 program design in
diabetic hypertension. MC-4232 has successfully
completed a randomized, placebo and active-controlled,
double-blind, 120-patient, 16-week, dose-ranging Phase 2
trial in diabetic hypertension. Although the trial was only
designed to suggest an optimal dose of MC-4232 rather
than to evaluate its efficacy, the best-performing dose
demonstrated statistically significant improvements vs.
baseline in four of the numerous pre-specified endpoints,
as well as trends towards improvements vs. baseline and
vs. active control in several endpoints. For the sake of
conservatism, we assign no value to MC-4232 at this
time, despite its early signs of efficacy, as it has not yet
unambiguously demonstrated efficacy vs. active
control—although admittedly this is more likely due to
the dose-ranging design of the trials conducted thus far
than it is due to any shortcomings of the agent.
MC-4262 is a combination of MC-1 and an unidentified
angiotensin receptor blocker (ARB) currently in Phase 1
trials for metabolic-syndrome hypertension. MC-45308
is a molecule unrelated to MC-1 undergoing preclinical
evaluation for thrombosis. MC-5422 is the first of
several MC-1 variations MCU is studying and has not yet
entered preclinical testing. No value is assigned to any of
these compounds at this time due to the lack of Phase 2
data thus far.
5
Medicure, Inc. (MCU - US$1.24) 04/24/07
Price target rationale
In addition to our sales assumptions, we believe, as will
be detailed below, we have been reasonably conservative
throughout our model. For example, we assume greater
share count dilution than has occurred historically, and a
greater tax rate in profitable years than MCU suggests.
We conservatively model fully-taxed diluted EPS of
US$0.41 and US$0.62 in the twelve-month periods
ending in November of 2012 and November of 2013,
respectively.
Our US$3 2007 price target is an average of two 2007
price targets. We apply a 30x multiple to our Nov-2012
estimate and discount by 40% for four years to attain a
2007 price target of US$3.20; we apply a 25x multiple to
our Nov-2013 estimate and discount by 40% for five
years to attain a 2007 price target of US$2.90. We
believe that each of the aforementioned multiples is
conservative, as they imply PEG ratios of less than 0.5 for
the 2013-based target and less than 0.2 for the 2012-based
target. We believe the 40% discount rate we have
selected is conservative given the strength of the data thus
far for MC-1 in CABG surgery, and the early signs of
success with Aggrastat re-launch efforts. The average of
these two 2007 price targets is slightly greater than our
official 2007 price target of US$3. (If we were to model
flat Aggrastat market share going forward, our new 2007
price target would still imply approximately 100%
upside. If the Phase 3 CABG surgery trial of MC-1 were
to be successful, we would lower our discount rate to the
low-20s, which would raise the 2007 present value of
what would then be our 2008 price target to between
US$5 and US$6, not including whatever value might
have emerged in the meantime from the pipeline.)
Company Background
Medicure, Inc. (MCU) is a commercial-stage and research
and development-stage pharmaceuticals company.
Medicure was founded on September 15, 1997, to acquire
the discoveries of Dr. Naranjan Dhalla of the University
of Manitoba, which would eventually form the basis for
the development of MC-1, currently MCU’s most
advanced pipeline candidate. Dr. Dhalla and Dr. Albert
Friesen, the current CEO of MCU, were among the
principal owners of Medicure at the time of its founding.
The MC-1 technology had originally been licensed by the
University of Manitoba to Genesys Pharma, Inc., a
consulting firm owned entirely at the time by Dr. Friesen,
on August 18, 1997. Genesys transferred the technology
at minimal cost to Medicure on September 26, 1997. On
August 30, 1999, Medicure completed a new license
agreement with the University of Manitoba in order to
modify slightly the terms of the original agreement
transferred from Genesys.
On November 22, 1999, Medicure was acquired by Lariat
Capital, led at the time by Dr. Friesen, in an arm’s length
transaction through a reverse takeover. As a result of the
merger, control of Lariat passed to the former
shareholders of Medicure. Lariat had been incorporated
on June 3, 1997, for the purpose of acquiring a project or
company through a reverse takeover. Lariat went public
on the Alberta Stock Exchange in March of 1999. On
December 22, 1999, Medicure and Lariat were
amalgamated as Medicure, Inc., resulting in Medicure,
Inc.’s assumption of Lariat’s listing on the Alberta Stock
Exchange. In December of 2002, Medicure, Inc. listed on
the Toronto Stock Exchange under the ticker, MPH.
Medicure, Inc. listed on the American Stock Exchange in
February of 2004 under the ticker, MCU.
At this time, MCU’s commercial portfolio consists of
Aggrastat, a GP IIb/IIIa inhibitor for use in ACS, for
which MCU obtained US rights from MOGN in August
of 2006. MCU’s most advanced pipeline product is MC-1,
an unpartnered, highly novel agent, in Phase 3 for use
in CABG surgery, and in pre-Phase 3 and earlier stages of
clinical development for other acute cardiovascular
indications. MCU’s pipeline includes several other
unpartnered cardiovascular compounds, both chronic and
acute, at various stages of development, from pre-clinical
to pre-Phase 3, of which some are combinations of MC-1
with other agents while others are not based on MC-1.
MCU enjoys a highly experienced executive team, led by
CEO Dr. Albert Friesen. Dr. Friesen earned a Ph.D. in
protein chemistry at the University of Manitoba. Dr.
Friesen was a founding executive of Rh Pharmaceuticals,
where he oversaw the development and approval of
WinRho, one of his two successful NDAs; Rh
Pharmaceuticals was eventually acquired by Cangene
(CNJ.to, Not Rated). Among other firms, Dr. Friesen has
also played a founding executive role at ABI
Biotechnology, eventually acquired by Apotex (private),
and Novopharm Biotech, now Viventia (private). MCU’s
Scientific Advisory Board includes Dr. A. Michael
6
Medicure, Inc. (MCU - US$1.24) 04/24/07
Lincoff of the Cleveland Clinic, as well as several other
acknowledged thought leaders in cardiology.
Aggrastat
At this time, MCU’s commercial portfolio consists of
Aggrastat, generically known as tirofiban hydrochloride.
Aggrastat is an antagonist of the platelet glycoprotein
IIb/IIIa receptor, also known as a GP IIb/IIIa inhibitor.
MCU obtained US rights to Aggrastat from MOGN in
August of 2006 for a purchase price of US$19M plus the
value of assumed inventory, as well as the assumption of
the royalty owed the inventor of the molecule, MRK.
MCU owes MRK a moderate royalty on US sales of
Aggrastat: 5% on sales of up to US$25M annually, 10%
on sales from US$25-50M, 12% from US$50-75M, 14%
from US$75-100M, and 20% on sales greater than
US$100M annually. MCU currently commercializes
Aggrastat in the US, and has actively promoted the agent
with its own internal salesforce since November of 2006;
MCU did not immediately actively promote Aggrastat
after acquiring it in order to allow wholesaler inventory
levels of the agent to return to historical, approximately
one-month levels.
Like another of the GP IIb/IIIa inhibitors, Integrilin from
SGP, Aggrastat is indicated for use in ACS or PCI in
combination with the anticoagulant, heparin; the third GP
IIb/IIIa inhibitor, ReoPro from LLY, is indicated for use
in ACS in combination with heparin only when PCI is
planned within 24 hours. The antagonism of the platelet
glycoprotein IIb/IIIa receptor impedes clotting, making
these agents useful additions to heparin in these
indications. The GP IIb/IIIa class saw its penetration of
the ACS market decline for several years, up until
recently. This decline was primarily due to the
emergence during that period of additional anticoagulant
options for ACS besides heparin; as GP IIb/IIIa inhibitors
had not been studied in combination with these newer
anticoagulants, their use fell while the use of these
alternative anticoagulants rose.
GP IIb/IIIa penetration of the ACS market has stabilized
in the low-20s recently as the agents’ core use in PCI has
proven resilient despite the emergence of alternative
anticoagulants in ACS. MCU’s acquisition of US
Aggrastat rights appears therefore to have been very well-timed.
Our due diligence suggests that the current
penetration will remain stable in the future. The recent
hue and cry over the long-term equivalence of outcomes
data for bare-metal stents and for drug therapy as an
alternative to PCI is unlikely to spell the end of the
procedure anytime soon; physicians will probably cling to
the hope that drug-coated stents, commonly used in PCI
today, would have fared better than their bare-metal
predecessors vs. drugs alone. Relatedly, as yet further
new anticoagulants are approved for ACS, they are
unlikely to stem the tide of PCI.
Although Aggrastat’s share of the GP IIb/IIIa class fell
while the penetration by the class of the ACS market was
declining, Aggrastat’s share has increased markedly over
the last few quarters—MCU’s initial efforts to promote
the agent appear to have met with success thus far. Our
due diligence suggests that the main culprit behind
Aggrastat’s share decline was its lack of promotional
emphasis. Aggrastat was never the primary focus of
whichever salesforce was promoting it any given moment
in the US until MCU acquired the agent. Both MOGN
and its predecessor, Guilford Pharmaceuticals, promoted
Aggrastat within a broad portfolio of other, non-cardiovascular
hospital products; obviously MRK also
enjoyed other demands on its attention besides Aggrastat.
MCU’s initial Aggrastat promotional efforts have likely
been bolstered by the presentation at the 2006 American
Heart Association meeting of a large, retrospective
dataset that suggests single high-dose bolus Aggrastat’s
non-inferiority vs. ReoPro across a number of important
clinical endpoints. Trends observed in this dataset
suggest if anything the superiority of Aggrastat vs.
ReoPro in the endpoints of death (0.7% vs. 1.7%,
respectively, p-value of about 0.40) and
thrombocytopenia (1.3% vs. 2.8%, respectively, p-value
of about 0.26). This presentation occurred shortly after
MCU acquired US Aggrastat rights. Additionally,
Aggrastat is known to be the fastest-reversing of the GP
IIb/IIIa inhibitors, which means that any if its recipients
who later have to undergo CABG surgery will need their
surgery delayed the least to allow time for their platelet
functions to return to normal.
The growing awareness of Aggrastat’s clinical
equivalence at least vs. its competitors meshes well with
the agent’s cost advantage. While all three GP IIb/IIIa
inhibitors are injectible agents, Aggrastat is the only
small-molecule therapy among the GP IIb/IIIa inhibitors;
7
Medicure, Inc. (MCU - US$1.24) 04/24/07
Integrilin is a large-molecule peptide chain and ReoPro is
an antibody. Accordingly, Aggrastat enjoys a pricing
advantage vs. these harder-to-manufacture large molecule
agents: MCU sells Aggrastat for US$400-500 per course
of therapy, whereas Integrilin and ReoPro retail between
US$1,200-2,000 per course of therapy.
We believe that our sales assumptions for Aggrastat are
conservative. We assume that the GP IIb/IIIa class will
maintain its current, stable penetration of the ACS
market. We assume that Aggrastat will very gradually
increase its share of the GP IIb/IIIa class, reaching only
17% volume-share in mid-2013, its seventh full year of
active detail by the MCU salesforce. We feel this is
conservative, as Aggrastat is the class leader in Europe,
and held 17% volume-share in the US as recently as 2003
(the year in which MRK divested the product to
Guilford). Additionally, as discussed above, our due
diligence suggests that Aggrastat arguably has not in
several years, if ever, been as high a priority for any US
salesforce as it is now for MCU’s; and, that Aggrastat
appears to offer at least equivalent efficacy to its
competitors at a lower price.
Aggrastat enjoys composition of matter patent protection
into 2013. Additional Orange Book-listed patents extend
into 2019, and a final patent on the use of a single high-dose
bolus of the drug reaches out to 2023. MCU is in
the process of negotiating with the FDA about adding
single high-dose bolus Aggrastat to the product’s label,
and hopes eventually to do a prospective trial of this
version of the agent.
MC-1
Background
MCU’s lead drug candidate, MC-1, is an orally available,
small-molecule, P2 purinergic (P2x) receptor antagonist.
MC-1 is a metabolite of Vitamin B6. To attain the
biolevels of MC-1 through Vitamin B6 administration
and subsequent metabolism that direct administration of
MC-1 attains, Vitamin B6 would have to be dosed at
levels orders of magnitude higher than those at which it is
known to cause dose-limiting neurotoxicity. MC-1 has
been given at doses three to four times higher than the
levels currently being explored in Phase 3 trials for up to
16 weeks in humans and up to nine months in dogs, with
none of the side effects of Vitamin B6 observed (nor with
any side effects observed different from and/or greater
than those seen in placebo controls). In fact, MC-1
appears to produce neuroprotective effects opposite to
those of Vitamin B6, suggesting another metabolite of the
latter besides MC-1 is responsible for its neurotoxicity.
P2x receptors are found on the surfaces of
cardiomyocytes in the heart, glial cells in the brain, and
endothelial cells and macrophages throughout the body.
In endothelial cells and macrophages, P2x receptors
appear to play a role in modulating inflammatory activity.
In cardiomyocytes and glial cells, P2x receptors appear to
be agonized endogenously by adenosine 5’-triphosphate
(ATP), one of the primary carrier molecules for
intracellular energy transfer in the body. When agonized
by ATP, P2x receptors open calcium channels (not all
calcium channels are P2x-mediated, but all P2x receptors,
at least in cardiomyocytes and glial cells, mediate calcium
channels).
Our due diligence suggests that in a healthy person, this
ATP-activated P2x-mediation of calcium channels helps
to induce the contraction of tissues composed of
cardiomyocytes, i.e., to pump blood. In an individual
suffering an ischemic event, however, cellular stress
triggers an overabundance of ATP, which in turn causes
excessive P2x-mediated calcium-channel opening. This
leads to a surplus of calcium-ion transport into
cardiomyocytes, which might exacerbate their damage
and therefore the ischemic event itself. MC-1
antagonizes the P2x receptor, preventing the excessive
binding of ATP to it when administered to individuals
suffering an ischemic event, and therefore preventing the
surplus of ischemia-reinforcing calcium-ion transport into
already-damaged cardiomyocytes. While theoretically
this could result in an over-prevention of P2x-mediated
calcium-channel opening, thereby starving
cardiomyocytes of calcium ions minimally needed for
tissue contraction, this dose-limiting toxicity appears to
occur only at doses of MC-1 about 100 times greater than
those at which therapeutic activity is observed in patients
undergoing cardiac stress.
As discussed above, MCU was founded to in-license the
worldwide rights to MC-1, which had been discovered at
the University of Manitoba. Under the terms of its
license, MCU owes the University up to a 3.9% royalty
on sales of MC-1, but faces no other requirements (no
milestones, etc.). MC-1 is unpartnered at this time,
although MRK has acquired the ex-North America right
8
Medicure, Inc. (MCU - US$1.24) 04/24/07
of first refusal for any combination of Aggrastat and MC-1.
MRK negotiated this option in the course of MRK’s
approval of MOGN’s sale to MCU of US rights for
Aggrastat; MRK had retained the right to review and
ultimately authorize any Aggrastat transaction made by
MOGN. MC-1 enjoys several issued method patents
regarding the targeting of the P2x receptor to treat
ischemia that extend into 2015/2016, as well as several
issued drug-specific use patents that last until 2017.
Several formulation patents, some of which pertain to
specific dose levels, are pending for MC-1; if issued on
schedule in 2008 they will protect the compound until
2025.
MC-1 CABG surgery indication
MC-1’s most advanced indication is CABG surgery, for
which the agent is currently in a Phase 3 trial under a
SPA with the FDA. The proposed cardioprotective
method of action of MC-1 relevant in CABG surgery is
the prevention, via P2x-receptor antagonism, of ischemia
reinforcement by calcium-ion transport, as described
previously. MCU began enrolling this 3,000-patient
Phase 3 trial of MC-1 in November of 2006, and targets
enrollment completion in November of 2007, data release
in March of 2008 (an earlier, interim DSMB examination
of the data is scheduled), and MC-1 NDA submission for
CABG surgery in June of 2008.
Data from a randomized, placebo-controlled, double-blind,
dose-ranging, 900-patient Phase 2b trial of MC-1 in
CABG surgery were reported in December of 2005. In
that trial, the regimen of MC-1 currently being pursued in
Phase 3 (250mg pre/post-op, then once daily for 30 days)
demonstrated a statistically significant 37% reduction in a
composite of cardiovascular-related death, non-fatal MI,
and non-fatal stroke at post-operative day 30 vs. placebo
(p-value less than 0.03); maintained a statistically
significant reduction of similar size in that composite vs.
placebo throughout a follow-up period out to post-op day
90; and displayed an equivalent adverse event profile vs.
placebo. These data were attained using a definition of
MI of peak CK-MB as determined by blood test of at
least 100ng/mL (CK-MB is an enzyme released by
cardiomyocytes that have burst in the course of dying; it
is considered an effective, proportionate marker of the
extent of cardiomyocyte death). MI itself was reduced
47% by 250mg daily of MC-1 with a p-value less than
0.01 with this definition.
MI is somewhat subjectively defined; different peak CK-MB
levels can be used to determine the MI threshold.
The 100ng/mL level, however, has been accepted by the
FDA as an appropriate MI threshold in the SPA for the
MC-1 Phase 3 CABG surgery trial. Furthermore, this
level had previously been condoned by the FDA in other
clinical programs examining cardioprotective agents,
such as the cariporide trials conducted by Aventis (now
Sanofi-Aventis, SNY, Not Rated) and the pexelizumab
studies conducted by Alexion (ALXN, Not Rated) and its
partner, Procter & Gamble (PG, Not Rated).
Nonetheless, the MC-1 Phase 2b CABG surgery trial’s
protocols initially defined MI as peak CK-MB of at least
50ng/mL. MCU chose this definition so that a higher
event rate would occur than with a more stringent, more
typical MI threshold, thereby allowing the capital-constrained
firm to avoid having to recruit thousands of
patients for a proof of concept trial. This strategy worked
too well, however; with such a loose definition of MI, so
many events occurred in every trial arm that MC-1 did
not separate sufficiently from placebo. Under the
50ng/mL definition, 250mg of MC-1 attained only mid-teens
reductions in composite events and in MIs
specifically vs. placebo, with p-values of about 0.3.
Physicians advising MCU on the Phase 2b MC-1 trial in
CABG surgery, who hailed from such respected
institutions as Duke University and Montreal Heart
Institute, recommended that the firm reanalyze the data
with a more stringent, more typical MI threshold. They
did not make this recommendation out of any desire to
game the results in MCU’s favor; rather, they observed
that the 26% placebo event rate seen in the study under
the 50ng/mL definition of MI greatly exceeded the
historical placebo event rates from other trials, which
were typically in the teens.
Furthermore, they noted that individuals suffering MIs
under the 50ng/mL definition in other studies had been
observed to experience cardiovascular mortality in only
the low-single digits within 90 days post-CABG surgery,
i.e., at a similar or lower rate than that of the real-world
post-CABG surgery population, which endures a mid-single
digit rate of one-year post-CABG surgery
cardiovascular mortalities, of which the vast majority
occur in the first 90 days post-op. Intuitively, patients
suffering MIs ought to experience greater death rates than
the overall population, which includes patients who do
not suffer MIs; when this does not occur, the MI
9
Medicure, Inc. (MCU - US$1.24) 04/24/07
threshold has likely been set incorrectly low. Data from
these other studies suggest a more appropriate threshold
for MI might be as low as 60-100ng/mL, as at that level, a
90 days post-CABG surgery cardiovascular mortality in
the mid-single digits has been observed. At 100ng/mL or
greater, 90 days post-CABG surgery cardiovascular
mortality in the low-double digits has been observed.
Following their recommendation, MCU reanalyzed the
very blood samples that had been used to attain the initial
results, again in a double-blind fashion, but now under
two alternate definitions of MI: peak CK-MB levels of at
least 70ng/mL and of at least 100ng/mL. Under the
70ng/mL definition, the 250mg dose of MC-1 reduced
composite events by 32% vs. placebo, with a p-value less
than 0.035; MIs specifically were reduced 38% vs.
placebo, with a p-value less than 0.02. As previously
discussed, under the 100ng/mL definition, the 250mg
dose of MC-1 reduced composite events by 37% vs.
placebo, with a p-value less than 0.03; MIs specifically
were reduced 47% vs. placebo, with a p-value less than
0.01.
We take great comfort in the FDA’s granting of a SPA for
the ongoing Phase 3 trial of MC-1 in CABG surgery in
light of the aforementioned MI threshold issues. The
Phase 3 trial very closely follows the protocol of the
Phase 2b trial, with a few key differences. Only the
250mg dose of MC-1 is being studied; an additional dose
was explored in the Phase 2b trial. Up to 3,000 patients
are being enrolled in the Phase 3 trial, rather than the 900
recruited into the Phase 2b study; this, combined with the
pursuit of only a single MC-1 dose, greatly increases the
Phase 3 trial’s power over that of the Phase 2 trial. MI is
prospectively defined as peak CK-MB of at least
100ng/mL in the Phase 3 trial, the definition at which the
greatest MC-1 effect was observed in Phase 2b study.
Finally, stroke has been eliminated as a component of the
composite endpoint in the Phase 3 trial; were stroke to
have been omitted from the Phase 2b study, the 250mg
dose of MC-1 would have reduced composite events vs.
placebo by 42%, with a p-value of about 0.01.
Our due diligence has determined that the results attained
in the Phase 2b CABG surgery trial of MC-1 suggest that
MCU had probably substantially underestimated the
actual effect size of the agent in planning that trial, thus
overpowering it. That MCU defined MI initially as
50ng/mL for fear of not having enough patients in the
trial to attain significant results with a more stringent MI
threshold, but subsequently achieved the aforementioned
results for MI definitions of 70ng/mL and 100ng/mL,
further suggests that MCU had underestimated MC-1’s
effect size. The Phase 3 CABG trial nonetheless assumes
the same MC-1 effect size as was input into the Phase 2b
trial design, and is probably therefore better powered than
its ostensible 85% power to detect a 20% reduction in the
composite endpoint. Regardless, the Phase 3 trial is
much better powered than the successful Phase 2b trial,
due to its size, its exploration of only a single dose of
MC-1, and its elimination of stroke from the composite
endpoint. Accordingly, we believe that the current Phase
3 CABG surgery trial of MC-1 will be successful.
Nonetheless, in light of the aforementioned MI threshold
issues in the Phase 2b trial, we are discounting our MCU
estimates by a healthy 40% annually to attain a price
target we feel is conservative.
We believe that after completing this trial, MCU will
attain a commercial partner for MC-1 outside the US, but
will retain US rights to the drug and market it through its
existing US Aggrastat salesforce. With US$22M of net
cash, MCU has sufficient resources to conclude this trial.
Based upon MCU’s aforementioned target of a June of
2008 NDA filing of MC-1 for CABG surgery, we expect
MCU will launch MC-1 in the US in mid-2009, and
MCU’s partner will launch MC-1 ex-US one year later.
As MCU has received fast-track designation for MC-1 in
CABG surgery (as well as in other indications), the NDA
might receive expedited review; accordingly, we feel our
expectation of a mid-09 US launch of MC-1 is
conservative.
We believe that our sales assumptions for MC-1 in
CABG surgery are also conservative. We assume that the
agent will garner slightly less than a one-half
penetration/share of the US CABG surgery market in
mid-2014, after five full years on the market; we model
half that trajectory for the EU market, beginning one year
later as previously discussed. We believe this assumption
would be highly conservative if MC-1 were to succeed in
its current Phase 3 trial, as it would then offer a unique
mechanism by which to reduce death and/or MI in CABG
surgery patients. We further assume that the price of a
course of MC-1 therapy will be set initially at only
US$600 per course of therapy, about 25% above the price
of a course of Aggrastat therapy (despite the latter being
60-75% cheaper than the other GP IIb/IIIa inhibitors), and
10
Medicure, Inc. (MCU - US$1.24) 04/24/07
will undergo minimal price increases. We feel that this
assumption too would be highly conservative if MC-1
were to succeed in its current Phase 3 trial.
Additional MC-1 indications
MC-1 has received fast-track designation for not only
CABG surgery, but also for ACS and for PCI. MCU has
successfully completed a Phase 2a trial of MC-1 in PCI,
in which periprocedural CK-MB levels were reduced by
MC-1 administration vs. placebo by about 30%, with a p-value
of about 0.035. However, as this was only a
biomarker-endpoint trial, and MCU intends to pursue
MC-1 in Phase 3 next in ACS (admittedly a closely
related indication to PCI), we assign no value to MC-1 in
ACS or PCI at this time for the sake of conservatism.
This is likely excessively conservative, as the biomarker
CK-MB is known to be closely correlated with
meaningful clinical endpoints, as discussed previously.
MCU intends to begin enrolling a Phase 3 trial of MC-1
in ACS within three to six months of successfully
completing the Phase 3 trial of MC-1 in CABG surgery,
and anticipates concluding the ACS trial within 12-18
months, i.e. between June of 2009 and March of 2010.
MCU is also investigating MC-1 in a Phase 1 trial in
stroke, which at this time is omitted from valuation due to
the lack of Phase 2 data thus far.
Pipeline
Besides the aforementioned MC-1 indications, MCU also
possesses an unpartnered pipeline of other agents, from
pre-clinical to pre-Phase 3, addressing both acute and
chronic markets. Some of these agents are combinations
of combinations of MC-1 with other agents while others
are not based on MC-1.
Two combination products of MC-1 with other agents are
currently in clinical-stage testing. MC-4232 is a
combination of MC-1 and the ACE-inhibitor, lisinopril,
for which MCU is finalizing a Phase 3 program design in
diabetic hypertension. MC-4232 has successfully
completed a randomized, placebo and active-controlled,
double-blind, 120-patient, 16-week, dose-ranging Phase 2
trial in diabetic hypertension. Although the trial was only
designed to suggest an optimal dose of MC-4232 rather
than to evaluate its efficacy, the best-performing dose
demonstrated statistically significant improvements vs.
baseline in four of the numerous pre-specified endpoints,
as well as trends towards improvements vs. baseline and
vs. active control in several endpoints. The best-performing
dose of MC-4232 reduced systolic blood
pressure vs. baseline (147.0mmHg) by 12mmHg (p-value
less than 0.0001) and vs. lisinopril alone by 4.5mmHg (p-value
of 0.13); reduced diastolic blood pressure vs.
baseline (82.6mmHg) by 7.5mmHg (p-value less than
0.0001) and vs. lisinopril alone by 3.4mmHg (p-value of
0.06); reduced fasting serum glucose from baseline
regardless of lisinopril use by 1.5mmol/L for patients
with baseline of 7.8mmol/L (p-value of 0.03) and by
3.4mmol/L for patients with baseline greater than
10mmol/L (p-value unspecified); reduced triglycerides in
patients with at least 1.7mmol/L baseline values by 27%
(p-value of 0.04); reduced LDL-cholesterol vs. placebo
by 10.6mg/dL (p-value of 0.095); and reduced HbA1c in
patients with at least 8.0% baseline values regardless of
lisinopril use by over 0.6%-points (p-value of about
0.27). For the sake of conservatism, we assign no value
to MC-4232 at this time, despite its early signs of
efficacy, as it has not yet unambiguously demonstrated
efficacy vs. active control—although admittedly this is
more likely due to the dose-ranging design of the trials
conducted thus far than it is due to any shortcomings of
the agent.
MC-4262 is a combination of MC-1 and an unidentified
angiotensin receptor blocker (ARB) currently in Phase 1
trials for metabolic-syndrome hypertension. MC-45308
is a molecule unrelated to MC-1 undergoing preclinical
evaluation for thrombosis. MC-5422 is the first of
several MC-1 variations MCU is studying and has not yet
entered preclinical testing. No value is assigned to any of
these compounds at this time due to the lack of Phase 2
data thus far.
Model
In addition to our sales assumptions, we believe we have
been reasonably conservative throughout our model. We
assume that MCU will enjoy no pipeline advances. This
is conservative with regard to MCU’s revenues, as well as
its multiple. Admittedly, this assumption reduces R&D
expenses, which some might suggest is not conservative;
however, we feel we have kept R&D expenses adequately
high. Furthermore, despite MCU possessing substantial
net operating loss carry-forwards at this time, which will
only increase between now and profitability, we assume
that MCU will begin paying taxes in full in its first
quarter of profitability, at a greater tax rate than MCU
11
Medicure, Inc. (MCU - US$1.24) 04/24/07
suggests it will ever have to endure. Finally, with regard
to share count, we assume that MCU’s historical rate of
share dilution will increase. We conservatively model
fully-taxed diluted EPS of US$0.41 and US$0.62 in the
twelve-month periods ending in November of 2012 and
November of 2013, respectively.
Risks
Risks to the attainment of our estimates and price targets
include, but are not limited to, the following: the failure
of MC-1 to succeed in its Phase 3 CABG surgery trial;
the failure of MC-1 to receive FDA approval in a timely
fashion; the failure of Aggrastat to penetrate the ACS
market; the failure of MC-1 to penetrate the CABG
surgery market; the potential for inaccuracy in our
estimates of expenses; the potential for fluctuation in the
exchange rate of the US dollar vs. the Canadian dollar,
etc. 11
Medicure, Inc. (MCU - US$1.24) 04/24/07
suggests it will ever have to endure. Finally, with regard
to share count, we assume that MCU’s historical rate of
share dilution will increase. We conservatively model
fully-taxed diluted EPS of US$0.41 and US$0.62 in the
twelve-month periods ending in November of 2012 and
November of 2013, respectively.
Risks
Risks to the attainment of our estimates and price targets
include, but are not limited to, the following: the failure
of MC-1 to succeed in its Phase 3 CABG surgery trial;
the failure of MC-1 to receive FDA approval in a timely
fashion; the failure of Aggrastat to penetrate the ACS
market; the failure of MC-1 to penetrate the CABG
surgery market; the potential for inaccuracy in our
estimates of expenses; the potential for fluctuation in the
exchange rate of the US dollar vs. the Canadian dollar,
etc.edicure, Inc. (MCU - US$

Drug Evaluation medicure publication
10.1517/17425255.3.2.275 © 2007 Informa UK Ltd ISSN 1742-5255 275
Current strategies with
high-dose tirofiban
Debabrata Mukherjee † & Marco Roffi
† Gill Heart Institute, University of Kentucky, 326 Wethington Bldg, 900 S. Limestone, Lexington,
Kentucky 40436-0200, USA
The glycoprotein (GP) IIb/IIIa receptor is a platelet-specific adhesion receptor
that mediates the formation of platelet aggregates. Pharmacologic blockade
of the receptor is associated with a reduction in major cardiovascular adverse
events after percutaneous coronary interventions and in the setting of acute
coronary syndromes. Three intravenous GP IIb/IIIa receptor inhibitors are
available: abciximab, tirofiban and eptifibatide. Tirofiban is a small, synthetic
non-peptide, competitive GP IIb/IIIa antagonist with high specificity and high
affinity for the GP IIb/IIIa receptor. In a head-to-head comparison, tirofiban
10-µg/kg bolus followed by a 0.15-µg/kg/min infusion was found to be infe-rior
to standard dose of abciximab in patients undergoing percutaneous cor-onary
intervention. Insufficient platelet inhibition with low-dose tirofiban
may likely explain these results. Subsequently, a high-bolus dose of tirofiban
(25 µg/kg bolus) followed by standard infusion was tested and evidence sug-gest
that in this dosing tirofiban may be as effective as abciximab and have a
comparable safety profile. Therefore, high-bolus dose tirofiban may be an
appealing and cost-effective alternative to abciximab. However, further test-ing
is warranted given the short follow up and limited statistical power of
the available data.
Keywords: abciximab, acute coronary syndromes, glycoprotein IIb/IIIa receptor inhibition,
percutaneous coronary intervention, tirofiban
Expert Opin. Drug Metab. Toxicol. (2007) 3(2):275-280
1. Introduction
A large body of evidence supports the notion that platelet glycoprotein (GP) IIb/IIIa
receptor inhibitors effectively reduce major cardiovascular adverse events (MACE)
including death, myocardial infarction (MI) and urgent target vessel revasculariza-tion
(TVR) in patients undergoing percutaneous coronary intervention (PCI) [1].
Similarly, these agents have proven to be efficacious in the setting of acute coronary
syndromes (ACS) [2] and particularly for patients undergoing early PCI [3]. Three
GP IIb/IIIa inhibitors are available on the market namely, abciximab, tirofiban and
eptifibatide. In this review, the authors focus on tirofiban, a small-molecule GP
IIb/IIIa inhibitor, and address laboratory and clinical evidence supporting the newer
high-bolus dose (HBD) regimen.
2. Platelet glycoprotein IIb/IIIa receptor antagonists
The GP IIb/IIIa receptor, or α IIB/β 3 integrin, is the most abundant platelet mem-brane
GP found in humans and, as a platelet-specific adhesion receptor, has a broad
specificity for a number of ligands, most notably fibrinogen, von Willebrand factor
and prothrombin. Approximately 60,000 – 80,000 copies of the integrin are present
per platelet and the number increases as an internal pool becomes available during
platelet activation. The GP IIb/IIIa receptor mediates the formation of platelet
aggregates via von Willebrand factor and soluble fibrinogen. Platelet stimulation by
1. Introduction
2. Platelet glycoprotein IIb/IIIa
receptor antagonists
3. Dosing and
administration strategy
4. Clinical efficacy of high-bolus
dose tirofiban
5. Safety
6. Conclusion
7. Expert opinion

For reprint orders,
please contact:
ben.fisher@informa.com


Tirofiban
276 Expert Opin. Drug Metab. Toxicol. (2007) 3(2)
soluble agonists, such as thrombin, ADP and thromboxane
A2, causes conformational changes of the receptor with subse-quent
transformation from a low- into a high-affinity state,
allowing for ligand binding. This conformational change of
the receptor is not due to direct action of the agonists on the
receptor, but results from receptor-mediated stimulation of
intracellular signaling pathways that enhance ligand affinity.
GP IIb/IIIa antagonists are qualitatively different from classi-cal
antiplatelet agents, such as aspirin or clopidogrel. They do
not inhibit platelet activation (i.e., intraplatelet signal genera-tion
or conduction), but primarily act outside the platelet by
competing with ligand binding that is essential for platelet
bridging and aggregate formation [4].
2.1 Tirofiban
Tirofiban (L-tyrosine-N-(butylsulfonyl)-O-[4-(4-piperidine-butyl)])
is a nonpeptide tyrosine derivative with a molecular
weight of 495 Da that is administered as an intravenous
infusion [5]. The volume of distribution is in the range of
21 – 87 l, and binding to human plasma proteins is modest at
64%. Metabolism in humans is negligible, and most drug
(.65%) is excreted renally with systemic clearance in the
range of 4.8 – 25.8 l/h. Renal function influences the excretion
of tirofiban and halving of the dose is recommended in
patients with creatinine clearance < 30 ml/min. Conversely,
concurrent disease or other drugs generally used in patients
affected by coronary artery disease do not seem to affect its
metabolism. The IC 50 value of tirofiban for inhibition of plate-let
aggregation is 0.011 µmol/l (5.45 µg/l) [6]. Following intra-venous
administration, tirofiban inhibits platelet aggregation
dose dependently, but dissociates rapidly from platelets and its
effect is reversed within 3 – 4 h after the end of infusion [6].
3. Dosing and administration strategy
Tirofiban has been tested in patients with ACS, administered
soon after hospital admission as part of the medical manage-ment
(upstream therapy) and at the time of PCI in patients
with stable and unstable coronary artery disease (downstream
therapy). The bolus regimen of tirofiban differed in the
upstream and downstream setting. For the upstream setting,
tirofiban was administered as 0.6 µg/kg of body weight/min
for 30 min in the Platelet Receptor Inhibition in Ischemic
Syndrome Management in Patients (PRISM) study [7] and
0.4 µg/kg/min for 30 min with heparin in the Platelet Recep-tor
Inhibition in Ischemic Syndrome Management in Patients
Limited by Unstable Signs and Symptoms (PRISM-PLUS) [8]
study. The tirofiban-only arm (without heparin) of the
PRISM-PLUS trial used a dose of 0.6 µg/kg, but was pre-maturely
stopped due to lack of efficacy. A total dose of
10 µg/kg, administered over 3 min, was used in the down-stream
setting in the Randomized Efficacy Study of Tirofiban
for Outcomes and Restenosis (RESTORE) [9] and in the Do
Tirofiban and ReoPro Give Similar Efficacy Outcomes
(TARGET) [10] trial. The PRISM study compared tirofiban
alone with heparin alone, and found a significant reduction in
the incidence of the composite primary end point of death,
MI, or refractory ischemia at 48 h in the tirofiban group [7],
and the PRISM-PLUS study showed that tirofiban with
heparin and aspirin was associated with a lower incidence of
ischemic events in patients with ACSs [8]. There was no bene-fit
with tirofiban alone in the PRISM-PLUS study [8]. Early
dose-finding studies of tirofiban did show > 85% ex vivo inhi-bition
of platelet aggregation by light transmission aggrego-metry
in response to a 10-µg/kg bolus plus a 0.15-µg/kg/min
infusion [11]. In the RESTORE trial, the primary composite
end point at 30 days was reduced from 12.2% in the placebo
group to 10.3% in the tirofiban group, a 16% relative reduc-tion
that was not statistically significant (p = 0.160). Thus,
the trial did not meet its primary end point at 30 days.
Nevertheless, the same bolus dose regimen was used in the
TARGET trial .
Despite a large body of evidence demonstrating improved
outcomes with the use of GP IIb/IIIa receptor inhibitors in
ACS patients undergoing PCI [7-9], head-to-head data among
the three available agents in this setting are lacking. In the only
comparative trial, the TARGET trial, the primary end point of
30 day composite end point of death, MI and urgent TVR was
significantly reduced with standard dose of abciximab
(0.25 µg/kg bolus and 0.125 µg/kg/min [maximum of
10 µg/min] infusion) compared with tirofiban (10 µg/kg bolus
followed by a 0.15 µg/kg/min infusion) in patients undergoing
PCI [10]. The lower incidence of adverse events was reflected,
in large part, by a reduction in periprocedural MI observed in
the first 12 – 24 h after PCI in the abciximab group. At 6- and
12-month follow up in the TARGET trial, tirofiban provided
a similar level of protection to abciximab against the composite
of death, MI and any target-vessel revascularization, but these
were secondary end points [12]. Mechanistic studies have sug-gested
that the reduced efficacy observed with tirofiban is
related to the inadequate platelet inhibition level achieved and
that a HBD of tirofiban (25 µg/kg) may be more clinically
effective. Accordingly, a study demonstrated that the inhibi-tion
of platelet function within 60 min of PCI was greater with
abciximab than with tirofiban given at the dose used in the
TARGET tri al [13], whereas other investigators showed that
after 2 h comparable inhibition of platelet function was
achieved with the two agents [14].
3.1 Platelet aggregation inhibition
On the base of these observations, recent mechanistic studies
have addressed higher doses of tirofiban in patients
undergoing PCI. Dose-finding studies demonstrated that a
25- µg/kg bolus plus the standard 0.15-µg/kg/min infusion of
tirofiban produced > 90% platelet inhibition by light trans-mission
aggregometry 15 – 60 min after the onset of treat-ment
[15]. Others have showed that the administration of the
same HBD of tirofiban was associated with a mean periproce-dural
level of platelet aggregation inhibition of > 80% [16].
Furthermore, comparable angiographic outcomes andMukherjee & Roffi
Expert Opin. Drug Metab. Toxicol. (2007) 3(2) 277
left-ventricular function recovery in ST-segment elevation MI
have been described with HBD tirofiban and abciximab
[16,17]. The prospective randomized Multicenter Registry of
High-Risk Percutaneous Coronary Intervention and Ade-quate
Platelet Inhibition (MR PCI) study was the first
head-to-head study comparing HBD tirofiban with dou-ble-
bolus eptifibatide and demonstrated greater platelet inhi-bition
with high-dose tirofiban compared with double-holus
eptifibatide (twice 180 µg/kg administration 10 min apart)
and standard infusion at 10 min and at 8 h [18].
4. Clinical efficacy of high-bolus dose tirofiban
Based on the suboptimal platelet inhibition detected after the
10-µg/kg-bolus regimen in ACS patients and improved inhi-bition
of platelet aggregation on subsequent dose-ranging
studies with HBD tirofiban, the tirofiban bolus dose was
raised from 10 to 25 µg/kg in the clinical setting, whereas the
infusion dosing, which demonstrated a good safety profile in
all previous clinical experience, remained unchanged. One
observational study reported that HBD tirofiban, followed by
0.15 µg/kg infusion, was well tolerated and resulted in no
excess of bleeding complications among 133 patients under-going
PCI [19]. The same investigators addressed safety and
efficacy of HBD tirofiban in 274 patients undergoing PCI
with HBD and found comparable results to a historical
cohort of abciximab-treated patients [20].
In the double-blind, placebo-controlled The Additive Value
of Tirofiban Administered With the High-Dose Bolus in the
Prevention of Ischemic Complications During High-Risk Coro-nary
Artery Angioplasty (ADVANCE) trial, 202 consecutive
patients pretreated with thienopyridines undergoing high-risk
PCI were randomized to HBD tirofiban or placebo immediately
before the procedure and then followed for a median time of
6 months for the occurrence of primary composite end point
(death, MI, TVR, and bailout use of GP IIb/IIIa inhibitors) [21].
The cumulative incidence of the primary end point was 35 and
20% in placebo and HBD tirofiban groups, respectively (hazard
ratio [HR]: 0.51; 95% confidence interval [CI]: 0.29 – 0.88;
p = 0.01). This difference was mainly due to the reduction of
MI and bailout use of GP IIb/IIIa inhibitors, with no significant
effect on TVR or death. The safety profile did not differ
between tirofiban and placebo. Importantly, the beneficial effect
of tirofiban was additive to thienopyridines and was consistent
across the whole spectrum of patients enrolled, with those
affected by ACS or diabetes showing a relatively greater benefit
from therapy. Again in the setting of ACS, there was no differ-ence
in 6-month MACE rates between HBD tirofiban and
abciximab among 229 non-randomized consecutive patients
undergoing early invasive strategy [22], and in the Randomized
Comparison of Upstream Tirofiban Versus Downstream High
Bolus Dose Tirofiban or Abciximab on Tissue-Level Perfusion
and Troponin Release in High-Risk Acute Coronary Syndromes
Treated With Percutaneous Coronary Interventions
(EVEREST) trial, tissue-level perfusion and extent myocardial
salvage were comparable in patients randomized to either HBD
tirofiban or abciximab (n = 61) [23].
With respect to acute MI and emergent coronary inter-vention
in this setting (primary PCI), Danzi et al. have
recently published the first head-to-head comparison between
HBD tirofiban and abciximab [17]. Abciximab, by virtue of its
salutary effect on tissue perfusion and coronary artery pat-ency,
is part of the recommended treatment strategy in acute
MI patients. In the study, 100 patients were randomized to
receive standard dose of abciximab or HBD tirofiban. The
end points, namely the change in infarct-zone wall motion
score index and left-ventricular ejection fraction at 30 days on
echocardiography, did not differ among the two groups. In
addition, in the HBD tirofiban group no major bleeding or
severe thrombocytopenia were observed and there was no
need for red blood cell transfusions.
One study addressed, in a randomized fashion, the efficacy
in terms of platelet-aggregation inhibition of four different
antiplatelet regimens in 112 patients with acute MI under-going
primary PCI [16]. The study showed that the mean
periprocedural platelet aggregation inhibition exceeded 80%
only in the HBD tirofiban group, further supporting the
appropriateness of the revised bolus dose of tirofiban also in
the primary PCI setting.
A strategy of HBD tirofiban-supported drug-eluting stent
implantation to abciximab plus bare-metal stent implantation
was compared among 175 patients undergoing primary PCI for
acute MI in terms of angiographic and clinical outcomes in the
High-Dose Bolus Tirofiban and Sirolimus Eluting Stent versus
Abiciximab and Bare Metal Stent in Acute Myocardial Infarc-tion
(STRATEGY) trial [24]. The investigators concluded that a
strategy of tirofiban-supported drug-eluting stent implantation
during primary PCI was safe and resulted in improved clinical
(decreased need for TVR) and angiographic (decreased resteno-sis
rate) outcomes compared with a strategy of abciximab-sup-ported
bare-metal stent implantation. Moreover, the HBD
tirofiban group had less thrombocytopenia. The cumulative
incidence of 8-month MACE (death, MI or TVR) was signifi-cantly
lower in the HBD tirofiban drug-eluting stent group than
in the abciximab bare-metal stent group (18 versus 32%, respec-tively;
HR: 0.53; 95% CI: 0.28 – 0.92; p = 0.043). The
composite end point of death/MI was similar in the two groups
(13 and 17%, respectively), but there was a significant reduction
in the HBD tirofiban drug-eluting stent group in the need for
TVR (7 and 20%, respectively; HR: 0.30; 95% CI: 0.12 – 0.77;
p = 0.01). However, much of the benefit in terms of MACE
reduction observed in the HBD tirofiban drug-eluting stent
groups was derived by the reduction in TVR expected with
drug-eluting stents and can, therefore, not be used to support
the HBD strategy. Markers of reperfusion, such as thrombolysis
in myocardial infarction (TIMI) flow patterns and cumulative
ST-segment resolution on echocardiogram, did not differ
between treatment arms, further supporting HBD tirofiban as
alternative GP IIb/IIIa antagonist to the current ‘gold standard’
abciximab in the setting of acute MI. The differential effects ofTirofiban
278 Expert Opin. Drug Metab. Toxicol. (2007) 3(2)
GP IIb/IIIa receptor inhibitors (HBD tirofiban versus abcixi-mab)
and stent types (bare-metal versus drug-eluting) is being
tested in the Multicentre 2x2 Factorial Randomised Study Com-paring
Tirofiban Administered With the Single High-Dose
Bolus Versus Abciximab and Sirolimus Eluting Stent Versus Bare
Metal Stent in Acute Myocardial Infarction (MULTI-STRAT-EGY)
trial, a multicenter, 2×2 factorial, randomized study
enrollling 600 patients with acute MI undergoing primary PCI.
The Tirofiban Evaluation of Novel Dosing versus Abcixi-mab
with Clopidogrel and Inhibition of Thrombin (TENA-CITY)
trial was designed to prospectively compare clinical
outcomes between HBD tirofiban and abciximab in > 4000
patients undergoing PCI, but was terminated prematurely
after enrolling 383 patients due to lack of funding [25]. This
was the only trial powered to address clinical equivalence
between the two GP IIb/IIIa receptor inhibitors. An analysis
of the available data showed no differences between HBD
tirofiban and abciximab (Tabl e 1 ) [25].
A meta-analysis of the available data suggested that HBD
tirofiban may be as effective as abciximab in patients under-going
PCI with a comparable safety profile [26]. The primary
end point in the analysis was the composite of death, MI and
urgent TVR at 30 days. Major and minor bleeding and the
incidence of thrombocytopenia were also assessed. A total of
1392 patients (689 allocated to tirofiban, 703 randomized to
abciximab) were included. The incidence of the combined
end point was 6.1% with HBD tirofiban and 7.3% with
abciximab (p = 0.46). There were also no differences between
the two groups in the individual end points of death, MI,
TVR, major or minor bleeding, or thrombocytopenia.
5. Safety
The most serious and frequent adverse effect related to the use
of GP IIb/IIIa receptor antagonists are bleedings and
thrombocytopenia. Risk of bleeding can be reduced by the use
of low-dose adjunctive unfractionated heparin, early sheath
removal and meticulous postprocedure care. In studies involv-ing
tirofiban, the incidence of any bleeding complications was
more frequent than heparin alone, but major bleeding com-plications
were not significantly different. Most of the
increases in bleeding occurred in patients who underwent
diagnostic catheterization or PCI, primarily at the femoral
artery access site. The incidence of thrombocytopenia,
defined as an absolute platelet count < 90,000/mm 3 , was
0.4% in PRISM and 1.9% in PRISM-PLUS trials. As a com-parison,
in patients receiving abciximab, the incidence of mild
thrombocytopenia (< 100,000/mm 3 ) is known to be in the
range 2.6 – 5.6%, whereas that of severe thrombocytopenia
(< 20,000/mm 3 ) is .0.1 – 0.5% of patients. In the TARGET
trial, there was no difference in terms of major bleeding
between the two study drugs, whereas minor bleeding and
thrombocytopenia were both lower in the tirofiban group [10].
In the STRATEGY trial, the use of tirofiban was associated
with a trend towards lower bleeding and to a statistically sig-nificant
reduction in the incidence of thrombocytopenia as
compared to abciximab, which suggests that increasing the
bolus dose of the drug, but not the infusion rate, has no or
negligible effect on the safety profile of the drug [24]. However,
the safety of the HBD tirofiban needs to be further tested in
larger, prospective trials. Importantly, HBD tirofiban has not
been tested in patients with renal insufficiency. For patients
with creatinine clearance < 30 ml/min, both in the upstream
and in the downstream setting, it is recommended to halve
the dose of the standard bolus and of the infusion.
6. Conclusion
Based on the available data, in patients undergoing PCI both
in the setting of stable and unstable coronary artery disease,
the use of HBD tirofiban (25-µg/kg bolus plus a
0.15-µg/kg/min infusion) appears to convey similar outcomes
Table 1. HBD tirofiban versus abciximab use or placebo in randomized studies.
Trials Population study Design Key information
ADVANCE [21] 202 high-risk patients undergoing
PCI
HBD tirofiban versus placebo Reduction of ischemic/thrombotic
complications
Danzi et al. [17] 100 STEMI treated with primary PCI HBD tirofiban versus abciximab Similar effects on angiographic results
and in the left-ventricular function
recovery
STRATEGY [24] 175 STEMI treated with primary PCI HBD tirofiban plus drug-eluting
stent versus abciximab plus
bare-metal stent
Similar effect and bleeding rate, but less
thrombocytopenia in the tirofiban group
EVEREST [23] 93 high-risk ACS patients
undergoing PCI
HBD tirofiban versus
standard-dose tirofiban versus
abciximab
Similar tissue-level perfusion and
myocardial salvage
TENACITY [25] 383 patients undergoing PCI HBD tirofiban versus abciximab Comparable safety and efficacy, but
underpowered
ACS: Acute coronary syndromes; HBD: High-bolus dose; PCI: Percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction. Mukherjee & Roffi
Expert Opin. Drug Metab. Toxicol. (2007) 3(2) 279
to standard-dose abciximab, with a comparable safety profile
and at lower costs. However, the short follow up and limited
sample size of the studies performed thus far do not allow for
established clinical equivalence. To that purpose, an
adequately powered randomized trial is needed.
7. Expert opinion
The data discussed herein suggest that HBD tirofiban effec-tively
inhibits platelet aggregation and appears at least equiva-lent
in efficacy to abciximab and double-bolus eptifibatide.
Despite lack of adequately powered, randomized, comparative
data, many clinicians are already using HBD tirofiban as
adjunct to PCI based on preclinical mechanistic data and
available clinical data. Although a meta-analysis of
.800 patients demonstrated no significant differences in
efficacy between HBD tirofiban and abciximab, adequately
powered, randomized clinical trials would provide more
definitive evidence. Furthermore, the landscape for optimal
antithrombotic therapy in the setting of PCI and ACS is rap-idly
changing with the introduction of newer agents, such as
bivalirudin and fondaparinux, and any incremental benefits of
GP IIb/IIIa inhibitors on top of these agents will need to be
reassessed in the future.
Bibliography
1. TOPOL EJ, BYZOVA TV, PLOW EF:
Platelet GPIIb-IIIa blockers. Lancet (1999)
353(9148):227-231.
2. BOERSMA E, HARRINGTON RA,
MOLITERNO DJ et al.: Platelet
glycoprotein IIb/IIIa inhibitors in acute
coronary syndromes: a meta-analysis of all
major randomised clinical trials. Lancet
(2002) 359(9302):189-198.
3. ROFFI M, CHEW DP, MUKHERJEE D
et al.: Platelet glycoprotein IIb/IIIa
inhibition in acute coronary syndromes.
Gradient of benefit related to the
revascularization strategy. Eur. Heart J.
(2002) 23(18):1441-1448.
4. SCHROR K, WEBER AA: Comparative
pharmacology of GP IIb/IIIa antagonists. J.
Thromb. Thrombolysis (2003) 15(2):71-80.
5. PEERLINCK K, DE LEPELEIRE I,
GOLDBERG M et al.: MK-383
(L-700,462), a selective nonpeptide platelet
glycoprotein IIb/IIIa antagonist, is active in
man. Circulation (1993)
88(4 Pt 1):1512-1517.
6. KONDO K, UMEMURA K: Clinical
pharmacokinetics of tirofiban, a nonpeptide
glycoprotein IIb/IIIa receptor antagonist:
comparison with the monoclonal antibody
abciximab. Clin. Pharmacokinet. (2002)
41(3):187-195.
7. NO AUTHORS LISTED: A comparison of
aspirin plus tirofiban with aspirin plus
heparin for unstable angina. Platelet
Receptor Inhibition in Ischemic Syndrome
Management (PRISM) Study Investigators.
N. Engl. J. Med. (1998)
338(21):1498-1505.
8. NO AUTHORS LISTED: Inhibition of
the platelet glycoprotein IIb/IIIa receptor
with tirofiban in unstable angina and
non-Q-wave myocardial infarction. Platelet
Receptor Inhibition in Ischemic Syndrome
Management in Patients Limited by
Unstable Signs and Symptoms
(PRISM-PLUS) Study Investigators. N.
Engl. J. Med. (1998) 338(21):1488-1497.
9. NO AUTHORS LISTED: Effects of
platelet glycoprotein IIb/IIIa blockade with
tirofiban on adverse cardiac events in
patients with unstable angina or acute
myocardial infarction undergoing coronary
angioplasty. The RESTORE Investigators.
Randomized Efficacy Study of Tirofiban for
Outcomes and REstenosis. Circulation
(1997) 96(5):1445-1453.
10. TOPOL EJ, MOLITERNO DJ,
HERRMANN HC et al.: Comparison of
two platelet glycoprotein IIb/IIIa inhibitors,
tirofiban and abciximab, for the prevention
of ischemic events with percutaneous
coronary revascularization. N. Engl. J. Med.
(2001) 344(25):1888-1894.
11. KEREIAKES DJ, KLEIMAN NS,
AMBROSE J et al.: Randomized,
double-blind, placebo-controlled
dose-ranging study of tirofiban (MK-383)
platelet IIb/IIIa blockade in high risk
patients undergoing coronary angioplasty.
J Am Coll Cardiol (1996) 27(3):536-542.
12. MUKHERJEE D, TOPOL EJ,
BERTRAND ME et al.: Mortality at 1 year
for the direct comparison of tirofiban and
abciximab during percutaneous coronary
revascularization: do tirofiban and ReoPro
give similar efficacy outcomes at trial 1-year
follow-up. Eur. Heart J. (2005)
26(23):2524-2528.
13. KABBANI SS, AGGARWAL A,
TERRIEN EF et al.: Suboptimal early
inhibition of platelets by treatment with
tirofiban and implications for coronary
interventions. Am. J. Cardiol. (2002)
89(5):647-650.
14. NEUMANN FJ, HOCHHOLZER W,
POGATSA-MURRAY G, SCHOMIG A,
GAWAZ M: Antiplatelet effects of
abciximab, tirofiban and eptifibatide in
patients undergoing coronary stenting. J.
Am. Coll. Cardiol. (2001) 37(5):1323-1328.
15. SCHNEIDER DJ, HERRMANN HC,
LAKKIS N et al.: Enhanced early inhibition
of platelet aggregation with an increased
bolus of tirofiban. Am. J. Cardiol. (2002)
90(12):1421-1423.
16. ERNST NM, SURYAPRANATA H,
MIEDEMA K et al.: Achieved platelet
aggregation inhibition after different
antiplatelet regimens during percutaneous
coronary intervention for ST-segment
elevation myocardial infarction. J. Am.
Coll. Cardiol. (2004) 44(6):1187-1193.
17. DANZI GB, SESANA M, CAPUANO C
et al.: Comparison in patients having
primary coronary angioplasty of abciximab
versus tirofiban on recovery of left
ventricular function. Am. J. Cardiol. (2004)
94(1):35-39.
18. MARDIKAR H, HIREMATH M,
MOLITERNO D et al.: Optimal Platelet
Inhibition in Patients undergoing PCI: data
from the Multicenter Registry of High-Risk
Percutaneous Coronary Intervention and
Adequate Platelet Inhibition (MR PCI)
Study. Annual Scientific Session American
College of Cardiology. New Orleans, USA
(March 2007).
19. DANZI GB, CAPUANO C, SESANA M,
BAGLINI R: Preliminary experience with a
high bolus dose of tirofiban during
percutaneous coronary intervention.
Curr. Med. Res. Opin. (2003) 19(1):28-33.
20. DANZI GB, CAPUANO C, SESANA M,
BAGLINI R: Safety of a high bolus dose of
tirofiban in patients undergoing coronary
stent placement. Catheter Cardiovasc. Interv.
(2004) 61(2):179-184. Tirofiban
280 Expert Opin. Drug Metab. Toxicol. (2007) 3(2)
21. VALGIMIGLI M, PERCOCO G,
BARBIERI D et al.: The additive value of
tirofiban administered with the high-dose
bolus in the prevention of ischemic
complications during high-risk coronary
angioplasty: the ADVANCE Trial.
J. Am. Coll. Cardiol. (2004) 44(1):14-19.
22. GUNASEKARA AP, WALTERS DL,
ARONEY CN: Comparison of abciximab
with ‘high-dose’ tirofiban in patients
undergoing percutaneous coronary
intervention. Int. J. Cardiol. (2006)
109(1):16-20.
23. BOLOGNESE L, FALSINI G, LIISTRO F
et al.: Randomized comparison of upstream
tirofiban versus downstream high bolus dose
tirofiban or abciximab on tissue-level
perfusion and troponin release in high-risk
acute coronary syndromes treated with
percutaneous coronary interventions: the
EVEREST trial. J. Am. Coll. Cardiol. (2006)
47(3):522-528.
24. VALGIMIGLI M, PERCOCO G,
MALAGUTTI P et al.: Tirofiban and
sirolimus-eluting stent versus abciximab and
bare-metal stent for acute myocardial
infarction: a randomized trial. JAMA (2005)
293(17):2109-2117.
25. INVESTIGATORS T: Tirofiban evaluation
of novel dosing versus abciximab with
clopidogrel and inhibition of thrombin
study. J. Am. Coll. Cardiol. (2007)
(In Press).
26. DAWSON C, MUKHERJEE D,
VALGIMIGLI M et al.: Meta-analysis of
high-dose single-bolus tirofiban versus
abciximab in patients undergoing PCI.
American Heart Association Scientific Sessions
2006. Chicago, USA (2006).
Affiliation
Debabrata Mukherjee †1 MD &
Marco Roffi 2 MD
† Author for correspondence
1 Gill Heart Institute, University of Kentucky,
326 Wethington Bldg, 900 S. Limestone,
Lexington, Kentucky 40436-0200, USA
Tel: +1 859 323 5630; Fax: +1 859 323 6475;
E-mail: Mukherjee@uky.edu
2 University Hospital, Department of Cardiology,
Zurich, Switzerland

MERRIMAN CURHAN FORD MCU
.
600 California Street
9th Floor
San Francisco, CA 94108
(415) 248-5600 Main
(415) 248-5690 Fax
(800) 909-7897 Trading
www.mcfco.com
April 17, 2007
Medicure, Inc. (MCU) Buy
An Undervalued Late-Stage Cardiovascular Biotechnology Company;
Initiating Coverage at Buy
• Unmet need for a cardioprotectant. Ischemic reperfusion injury
(IRI) is associated with a high risk of death, MI, heart failure, arrhythmia,
renal insufficiency, and stroke. All of these can add up to
a 20% incidence of major vascular events following CABG surgery.
• MC-1, Medicure’s lead product, is currently in the midst of a pivotal
Phase III trial for the treatment of IRI. This trial is being conducted
under the auspices of an SPA agreement with the FDA, which
reduces the regulatory risk of the product. We believe that this
product has a high probability of being partnered within the next
three years. Final Phase III data may be presented at next year’s
ACC in March 2008.
• AGGRASTAT is an undervalued asset, in our view. We believe
Medicure’s re-growth of this brand can generate solid revenues and
provide a commercial platform for the eventual launch of MC-1.
• Initiating coverage at Buy. We are valuing the company on a
modified sum-of-the-parts basis. We are projecting that the company
will re-grow the AGGRASTAT brand to C$23M in three years.
For MC-1, we are assuming a 2009 launch, under a co-promote
model in the United States. Based on these assumptions, we believe
the stock can trade towards the US$2.00-2.20 level in 12 months.

target is too low

Jose J Haresco, Ph.D.
Senior Vice President
(415) 248-5629
jharesco@mcfco.com
Medicure engages in the R&D and
commercialization of therapeutics
for cardiovascular needs. It develops
products for the treatment
of acute cardiovascular events,
such as acute coronary syndrome,
coronary artery bypass,
and graft surgery, as well as
heart attacks to chronic conditions,
including hypertension and
metabolic syndrome.
Market Cap (M): $139.4
Shares Out. (M): 111.0
Float (M): 106.2
10-Day Avg. Volume: 167,600
Institutional Ownership: 24.2%
Enterprise Value (M): $107.2
MCF Estimates
Market Data
Stock Performance
Company Description
Valuation (FY07E)
Key Metrics
Price: $1.20
Rating: Buy
52-Week Range: $0.91-1.91
Book Value/Share: 0.256
Debt/Capital: 21.7%
Debt (M): C$13.4
Cash (M): C$47
EV/Sales: NM
EV/EBITDA: NM
PEG Ratio: NM
Summary
Medicure is, in our view, an undervalued late-stage biotechnology
company in the cardiovascular sector. We believe that Medicure can
re-grow the AGGRASTAT brand to a conservative C$23M in three
years. The company’s lead product, MC-1, is currently in pivotal
Phase III for the treatment of ischemic reperfusion injury following
CABG surgery; the trial is being conducted under the auspices of the
SPA agreement with the FDA, which reduces regulatory risk, in our
view.
Investment Conclusion

April 17, 2007 2
Cardiology
Medicure, Inc. Buy
Company Description
Medicure is, in our view, an undervalued biotechnology company in the cardiovascular sector. The company
recently acquired AGGRASTAT, an injectible anti-platelet therapy for the treatment of acute coronary syndrome
(ACS). AGGRASTAT offers superior efficacy in diabetics at a much lower cost relative to its competitors,
ReoPro and Integrilin, but has for several years not been aggressively marketed. We believe that Medicure
can re-grow the product to a conservative C$23 million in three years. The AGGRASTAT franchise also
provides a platform upon which to launch future cardiovascular products. The company’s lead development
candidate, MC-1, is currently in pivotal Phase III for the treatment of ischemic reperfusion injury following
CABG surgery; the trial is being conducted under the auspices of SPA agreement with the FDA, which reduces
the regulatory risk, in our view. The company is headquartered in Manitoba, Canada. As of the publication
of this report, the company had approximately C$47 million in cash and equivalents.
Investment Highlights
Unmet need for a cardioprotectant. Ischemic reperfusion injury (IRI) is thought to be responsible for the
myocardial damage that can occur following a coronary artery bypass graft (CABG). IRI is associated with a
high risk of death, MI, heart failure, arrhythmia, renal insufficiency, and stroke after CABG surgery. All of
these can add up to a 20% incidence of major vascular events following CABG surgery.
Unique technology. We believe MC-1 blocks the signaling cascade that ultimately causes ischemic reperfusion
injury. It is has shown very promising results in multiple Phase II trials, and is currently in the midst of
a pivotal Phase III trial. This trial is being conducted under the auspices of an SPA agreement with the FDA,
which reduces the regulatory risk of the product, in our view. The upside to this product may be its eventual
use in percutaneous coronary intervention (PCI). We believe that this product has a high probability of being
partnered within the next three years.
AGGRASTAT is an undervalued asset, in our view. Medicure acquired AGGRASTAT in late 2006 from MGI
Pharma. Despite offering better efficacy in diabetics at a lower cost, AGGRASTAT sales have floundered due
to lack of a coherent commercialization effort. We believe Medicure’s re-growth of this brand can generate
solid revenues and provide a commercial platform for the eventual launch of MC-1.
Significant potential market opportunities. AGGRASTAT operates in the US$500 million U.S. platelet
inhibitor market. We believe that the market for MC-1 in the CABG setting is worth US$185 million in the
United States alone. The use of MC-1 in coronary artery stenting procedures provides another US$750 million
in market opportunities.
Initiating coverage at Buy. We are valuing the company on a modified sum-of-the-parts basis. We are
projecting that the company will re-grow the AGGRASTAT brand to C$23 million in three years. For MC-1, we
are using a risk-adjusted probability model of success. We are conservatively assuming a CY2009 launch using
a co-promotion model in which Medicure earns 40% of the revenue generated by the partnership/joint
venture in the United States. We are assuming 30% penetration of the market in the first year, which we
believe is reasonable given that there is no product in the market for use as a cardioprotectant. We are also
only assuming a probability of 60% success to the trial, despite the fact that it is a pivotal study being conducted
under an SPA. We believe the stock can trade toward US$2.00-2.20 in 12 months, and we are therefore

Pipeline Detail: AGGRASTAT
Medicure acquired AGGRASTAT (tirofiban hydrochloride) from MGI Pharma in August 2006. AGGRASTAT is a
glycoprotein (GP) IIb/IIIa inhibitor. AGGRASTAT inhibits platelet aggregation in a dose- and concentrationdependent
manner by preventing the binding of fibrinogen to the GP IIb/IIIa receptor, reducing the risk of
clot formation.
AGGRASTAT approved by the FDA for the treatment of acute coronary syndrome (ACS) including unstable
angina and non-Q-wave myocardial infarction. Acute coronary syndrome (ACS) is a broad set of symptoms
attributed to acute myocardial ischemia — chest pain due to a lack of blood flow to the heart resulting from
coronary artery disease (CAD). ACS covers a range of clinical conditions ranging from unstable angina to
non-Q-wave myocardial infarction and Q-wave myocardial infarction.
Originally developed by Merck, AGGRASTAT was launched in the United States in 1998, and is currently
available in 82 countries worldwide. Merck continues to market AGGRASTAT outside the United States, including
Europe where 2006 sales for AGGRASTAT were approximately US$95 million. Merck sold the U.S.
rights to AGGRASTAT to Guilford Pharmaceuticals Inc. in 2003, which was subsequently acquired by MGI in
2005. Total U.S. sales for the GP IIb/IIIa inhibitor class in 2006 were in excess of US$500 million, which included
US$8 million in AGGRASTAT sales.
Superior efficacy in diabetics. There are currently three GPIIb/IIIa compounds on the market. These include
Millennium Pharmaceuticals/Schering’s Integrilin (US$363 million in sales in 2006), Eli Lilly’s ReoPro
Product Clinical Indication Preclinical Phase I Phase II Phase III NDA Market
Aggrastat Acute Coronary Syndrome
MC-1 CABG Surgery
Acute Coronary Syndrome
Stroke
MC-4232 Diabetic Hypertension
MC-4262 Hypertension Complicated
w/ Metabolic Syndrome
MC-45308 Thrombosis
MC-5422 Ischemia Discovery
1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q
SPA Granted for MC-1
MC-1 Phase III Enrollment Completed
MC-1 Phase III Completed
MC-1 NDA Submitted
MC-1 Approval and Launch

(US$156.5 million in sales in 2006), and AGGRASTAT. Of these, Integrilin has the broadest indication; it is
approved for use both during and before PCI procedures, which largely accounts for its dominant market
share. All three drugs are intravenously delivered and have therefore been overshadowed by orally available
compounds like Bristol Myers Squibb’s Plavix (US$3.4 billion in sales in 2006).
AGGRASTAT is the most cost-effective of the three. It has superior efficacy in diabetic patients, is convenient
to use (Integrilin requires refrigeration), and part of the recommended treatment regime for Non ST-Elvated
ACS in the 2005 American Heart Association guidelines.
AGGRASTAT is More Effective in Diabetic Patients (Composite Endpoint)
Impact of AGGRASTAT on Mortality in Diabetic Patients
As effective and safe as ReoPro in PCI. The 2004 study by Danzi compared a high-dose bolus of AGGRASTAT
to Reopro in patients undergoing coronary stenting. The study compared two cohorts of patients
who underwent coronary stent placement between January 2000 and December 2002. In the first cohort,
ReoPro which was given to 280/802 (34.9%) of 802 stented patients; in the second cohort, AGGRASTAT was
administered to 274/716 (38.3%) stented patients.
The primary endpoints were the proportion of patients with major bleeding and the rate of site access complications.
The study also evaluated the 30-day incidence of major adverse cardiac events (MACE). After the
procedure, the patients were given Plavix for four weeks and aspirin on an ongoing basis. Major bleeding episodes
were observed in four patients receiving ReoPro and in none receiving AGGRASTAT (1.4% vs. 0%; P =
0.12); the rates of site access complications were similar (3.6% vs. 3.3%; P = 0.96). The 30-day incidence
of MACE was 7.1% in the ReoPro group and 5.8% in the AGGRASTAT group (P = 0.65). Thus, in patients
30-Day Death or MI in Diabetic Patients
TRIAL Compound IIb/IIIa Inhibitor Placebo p value
PRISM AGGRASTAT 8.1% 4.3% 0.04
PRISM-PLUS AGGRASTAT 15.5% 4.7% 0.00
PURSUIT Integrilin 18.8% 18.1% 0.70
GUSTO IV ReoPro 11.4% 10.3% 0.50
PARAGON A Lamafiban 16.2% 11.7% 0.21
PARAGON B Lamafiban 13.7% 13.0% 0.74
Source: Circulation 2001; 104; 2767-2771
30-Day Death in Diabetic Patients
TRIAL Compound IIb/IIIa Inhibitor Placebo p value
PRISM AGGRASTAT 4.2% 1.8% 0.07
PRISM-PLUS AGGRASTAT 6.7% 3.6% 0.17
PURSUIT Integrilin 6.1% 5.1% 0.33
GUSTO IV ReoPro 7.8% 5.0% 0.51
PARAGON A Lamafiban 6.2% 4.6% 0.93
PARAGON B Lamafiban 4.8% 4.9% 0.01
Source: Circulation 2001; 104; 2767-2771

undergoing coronary stenting, the high bolus dose of AGGRASTAT is as safe as ReoPro. Nevertheless, AGGRASTAT
is only approved for the treatment of ACS, and is not approved for use in PCI.
Market opportunity. The market for GP IIa/IIIb inhibitors should remain stable at the US$500 million level
until the end of the decade given its use in the PCI market, in our view. AGGRASTAT has previously suffered
from Merck and MGI’s lack of interest in driving AGGRASTAT product sales. Sales of AGGRASTAT under
Merck and then MGI fell from US$33.6 million in 2003 to US$12.3 million in 2005. By the time Medicure acquired
the product, virtually no sales and marketing dollars were being spent on the product. We believe that
Medicure’s investment of a proprietary 24 person sales force and marketing dollars can reinvigorate the
product. The product offers superior efficacy in diabetics at a 72% discount to ReoPro and a 43% discount to
Integrilin. The company is largely banking on off-label use to grow its franchise; for this reason we have kept
our estimates fairly conservative going forward. We believe that Medicure can re-grow the product to the
CAN$23 million level over the next 24 months.
MC-1
Background: vascular disease. Vascular disease (atherosclerosis) is a progressive and chronic condition
caused by the buildup of fatty cells in the inner lining of the vascular arteries, which turns into a localized,
patched, thickening, called a plaque or lesion. Expansion of the plaque into the interior of the artery (the lumen)
results in a narrowing of the artery (known as stenosis). The narrowing reduces blood flow to tissues
(such as the heart), which leads to tissue death (necrosis). Vascular disease can occur in arteries of any organ
of the body, and often leads to impaired organ function or death. Heart attacks, congestive heart failure,
kidney failure, or diabetes-related vascular diseases can all be caused by vascular disease.
Atherosclerosis in the coronary arteries is referred to as Coronary Artery Disease (CAD) or Coronary Heart
Disease (CHD). Coronary artery bypass graft surgery, or CABG, was the first treatment for CAD and involves
circumventing a blocked artery using a healthy vein or artery. Coronary artery bypass graft surgery is a surgery
in which one or more blocked coronary arteries are bypassed by a blood vessel graft to restore normal
blood flow to the heart. These grafts usually come from the patient's own arteries and veins located in the
chest, leg, or arm. The graft goes around the clogged artery to create new pathways for oxygen-rich blood to
flow to the heart. The goals of the bypass surgery are: 1) to relieve symptoms of coronary artery disease
(including angina), 2) Enable the patient to resume a normal lifestyle, and 3) lower the risk of a heart attack
or other heart problems.
This highly-invasive procedure is considered the standard care for CAD, but is associated with long hospital
stays and recovery times. In particular, it is associated with a high risk of death, MI, heart failure, arrhythmia,
renal insufficiency, and stroke. All these can add up to a 20% incidence of major vascular events following
CABG surgery.

Coronary Artery Bypass Graft Surgery
In coronary artery bypass graft surgery, a surgeon makes a vertical incision in the skin
and muscle in the middle of the chest and then cuts through the breastbone (sternum).
The surgeon spreads the rib cage to expose the heart and then cuts through the lining
that protects the heart (pericardium). To reroute blood flow around the diseased blood vessel,
surgeons typically use a portion of the saphenous vein in the leg or an internal mammary artery.
Source: health.yahoo.com
MC-1 Mechanism of Action
In order to perform CABG surgery, blood flow to the descending arteries is cut off for a short period of time.
A major source of vascular damage following CABG surgery is caused by the act of unblocking the blood flow
(reperfusion). During the earliest phases of reperfusion, cardiomyocytes (cells responsible for the heart’s
muscular contractions) undergo extreme contraction — sustained shortening and stiffening of the myocardium.
If this lasts for an extended period of time, cell death through apoptosis or necrosis can ensue. This
eventually aggravates the vascular problem and leads to immune-mediated vascular damage. This is known
as ischemic reperfusion injury, or IRI.
The core cause of ischemic reperfusion injury is thought to be the rapid release of extracellular ATP. At the
ischemic phase, ATP within the cell is depleted and cardiomyocytes accumulate Na+ via various pathways in
the membrane including the Na+ channel, the Na+/H+ exchanger, and the Na+/HCO3 symporter. Na+ cannot
exit the cell since the Na+/K-ATPase is rendered non-functional due to the lack of ATP. Na+ influx leads to
Ca2+ buildup since the Na+/Ca2+ exchanger (NCE) operates in reverse mode in a depolarized, Na+-overloaded
cell. Extracellular ATP from platelets and nerve endings further exacerbate the problem by binding to the P2
purnergic receptors, which also cause an influx of Ca2+ . Consequently, ischemic cells develop cytosolic Ca 2+
overload.
During reperfusion, the cell is re-supplied with ATP and it starts hoarding excess intracellular Ca2+. The overload
of intracellular Ca2+ has been implicated in several mechanisms that lead to irreversible cellular injury:
initiation of signaling cascades that lead to the activation of phospholipase A2 (PLA2), PLAC, endonucleases,
proteases, and several genes that control the cellular life cycle. These processes eventually lead to cell
death, which in turn causes further injury through activation of local, cytokine-mediated, immune responses.

Elevated Calcium Levels Contribute to Ischemic Reperfusion Injury
High intracellular concentrations of [Ca2+], have been implicated in several mechanisms
that lead to irreversible cell death, which in turn leads to local immune responses that aggravate vascular damage.
MC-1 can prevent this cascade by blocking Ca+ influx into the cell.
Source: FASEB Journal (1995) 9, 219-228; Cardiovascular Research (2004) 61, 365-371
MC-1 is a cardioprotectant. It prevents the cascade ischemic reperfusion cascade by stopping at one of its
core sources: it prevents extracellular ATP from binding to the P2 purinergic receptors and further increasing
the cytosolic [Ca2+ ] level. Blocking this cascade can prevent cell death, which in turn prevents further downstream
immune responses from aggravating the damage.
Multiple clinical studies demonstrate MC-1’s potential. MC-1 has been evaluated in several clinical
studies. Most recently, the MEND-CABG (Phase II/III) trial showed that MC-1 may mitigate adverse events
after CABG surgery.
MC-1 Trials
MEND-I. MEND-I was a double-blind, placebo-controlled study to evaluate MC-1’s ability to reduce cardiomyocyte
death as measured by changes in the MB fraction of the enzyme creatine kinase (CK-MB), which is
secreted from damaged cardiac muscles. CK-MB levels have been previously correlated with the risk of myocardial
infarctions.
Sixty patients were randomized in a 2:1 manner, receiving either MC-1 (10 mg/kg) or placebo prior to Percutaneous
Coronary Intervention (PCI) The primary endpoint was infarct size based on CK-MB measurements
24 hours after PCI. Secondary endpoints were the occurrence of major cardiac events (MACE) within 30 days
and occurrence of MI within 24 hours of PCI.
MC-1 showed a 43.5% reduction in infarct size (32.9 ng / ml, p=0.038). However, there no deaths in either
the placebo or experimental groups, so the occurrence of non-fatal MI was the same.
MEND-CABG I. MEND-CABG enrolled 901 patients in a placebo-controlled Phase II/III trial. Patients were
enrolled into three treatment arms: 250 mg MC-1, 750 mg MC-1, or placebo in a 1:1:1 manner. Patients received
treatment once a day for 30 days. The study enrolled high-risk patients that two of the following criteria: ACS within 28 hours, MI within seven days, TIMI 0-2 flow, angiographic evidence of thrombus, LVEF
<=30%, or saphenous vein graft lesion.
The primary composite endpoint included cardiovascular death, non-fatal MI defined by CK-MB levels >= 50
ng/ml and non-fatal cerebral infarction at post-operative day (POD) 30. The study was not powered to detect
significance, but merely show a trend towards significance. It was powered at 78% to detect a 37% reduction
in the primary endpoint. The trial failed to meet its primary endpoint under the definition of non-fatal MI
having CK-MB levels > 50 ng/ml, showing only a 14% reduction in MI under this definition. However, at a
definition of MI having CK-MB levels > 100 ng/ml, an alternative definition of MI, MC-1 showed remarkably
good results. MC-1 was well tolerated.
Exploratory Analysis of 100 ng/ml Definition of MI
Source: Medicure
MEND-CABG II (Pivotal Phase III). The company is in the midst of a pivotal Phase III trial that will enroll
3,000 high-risk CABG patients. In December 2006, Medicure announced that it had completed an SPA agreement
with the FDA. The study will be conducted in 120 sites across the United States and Europe, and uses a
composite endpoint and a definition of CK-MG >= 100 ng /ml as the definition of MI. The FDA had previously
allowed Alexion to use this definition in its ischemic reperfusion injury trials. Patients will be treated for 30
days and followed for an additional 90 days. Enrollment began in early 2007. As of April 12, 2007, over 90%
of sites were active; enrollment is on track to be completed in late 2007. Final Phase III data should be available
at next year’s Late Breaking ACC at the end of March 2008. We estimate that the company will file a
rolling NDA in 2007/2008 and launch the product in late 2008 or early 2009 at the latest.
Regulatory Pathway
We are optimistic about the outcome of this trial, particularly given that the SPA agreement lowers regulatory
risk, the trial’s similarity to MEND CABG-1, and the FDA’s agreement that an additional Phase III trial
will not be required. Furthermore, this product has been granted priority six-month review. The FDA has said
will allow MEND-CABG-1 data to be included in the submission.
The company has been in continuous contact with the EMEA regarding a European submission, and expects
to file for European approval shortly after an approval in the United States. What remains to be seen, however,
is whether the EMEA will require the company to perform an additional Phase III trial.
Timepoint Placebo
POD30 49 31 (37.2% difference, p=0.028) 34 (31.1% difference, p=0.071)
POD90 50 32 (36.5% difference, p=0.030) 35 (30.5% difference, p=0.071)
Incidence of MI Only
Timepoint Placebo
POD30 43 23 (47.2% difference, p=0.008) 23 (47.2% difference, p=0.008)
POD90 44 23 (48.3% difference, p=0.006) 23 (48.3% difference, p=0.006)
250 mg / day 750 mg / day
Composite Endpoint of Cardiovascular Death, MI, Stroke
250 mg / day 750 mg / day

There are approximately 370,000 CABG procedures performed in the United States every year, and there is
currently no product approved for use as a cardioprotectant during cardiovascular surgeries. The number of
CABG procedures, according to our channel checks with cardiovascular surgeons, has been increasing in recent
months given the controversies regarding drug eluting stents. We believe that the use of MC-1 in the
U.S. CABG setting, at a conservative price of US$750 per I believe the company will charge 1000 to 1500 not 750 dollars. Even if you use 750 times 370 thousand you get a market near 300 million not 185 milliontreatment, is worth US$185 million in the United
States alone.
An upside to this is MC-1’s potential use in Percutaneous Coronary Intervention (PCI). MC-1’s ability to prevent
local cellular damage during balloon catherization or stent deployment could be of significant clinical
value in the face of the recent debates surrounding long-term complications associated with drug eluting
stents. There were approximately 1 million PCI procedures performed in 2006 in the United States alone — a
potential additional market value of US$750 million for MC-1. It is unlikely that Medicure can pursue this indication
on its own. Rather, we believe that this indication is something a larger partner would have to fund.
We believe that solid results in Phase III for the PCI indication can lead to a strong commercialization partnership.
Procter & Gamble had previously signed a co-development partnership with Alexion Pharmaceuticals
prior to the initiation of Alexion’s Phase IIb trial for pexelizumab. The partnership was valued at US$95 million,
which included a US$10 million upfront payment, royalties, and milestones.
Competitive Landscape
There are two primary competitors in the injectible anti-platelet market: Millenium/Schering’s Integrilin and
Eli Lilly’s ReoPro. Integrilin was originally developed by Millenium Pharmaceuticals, but is co-marketed with
Schering Plough in the United States and licensed to GlaxoSmithKline overseas. Integrilin is approved for use
in both ACS and PCI — hence its dominant share; patients can be treated with Integrilin once they are admitted
to a hospital and can be kept on it until the PCI procedure. ReoPro is approved for use as an adjunct
therapy in addition to heparin and aspirin in percutaneous coronary intervention for the prevention of cardiac
ischemic complications, or in patients with unstable angina who are non-responsive to conventional medical
therapy if a PCI is planned within 24 hours. Integrillin is approved for the treatment of patients with acute
coronary syndrome (unstable angina/non-ST-segment elevation myocardial infarction), including patients
who are to be managed medically and those undergoing percutaneous coronary intervention (PCI), and for
the treatment of patients undergoing PCI, including those undergoing intracoronary stenting. In contrast,
Aggrastat is approved for use on in ACS and not PCI. We believe this narrow label, as well as the lack of
marketing effort, has contributed to the product’s lackluster performance prior to its acquisition by Medicure.
Despite the need for a cardioprotectant, there is little competition for MC-1. The two most notable products,
Aventis’ caroporide and Alexion’s pexelizumab, both failed in recent years to show any efficacy as a cardio-protectant. Frankly, we believe this is the primary reason for Medicure’s stock being undervalued relative to
its late-stage peers. We are not discouraged by these companies’ failures to develop a drug for use in preventing
ischemic reperfusion injury. We believe that both compounds failed because the mechanisms of action
were too specific to engender a broad reduction in the immunomodulatory response to ischemic reperfusion
injury. MC- 1 attempts to prevent injury at the beginning of the signaling cascade which leads to the
immune response, rather than trying to modulate the immune response itself.
There are a number of compounds in development, but most are being pursued by academic research institutions.
We highlight the competitive products being pursued by private and public companies in the table
below.
Competitive Landscape for Cardioprotectants
Source: MCF & Co.
MC-4232
MC-4232 combines MC-1 with lisonopril, an ACE inhibitor, and is targeted at the extremely competitive high
blood pressure market. Phase II (MATCHED) clinical trials demonstrated blood pressure and metabolic control.
The MATCHED trial enrolled 120 patients in a randomized, placebo-controlled, double-blind, crossover study.
100, 300, and 1000 mg of MC-4232 were combined with 20 mg of lisonopril (normal dosing range is 20-40
mg). The primary endpoint was mean daytime ambulatory systolic flow (MDASBP); the study was not powered
to detect significance. The 300 mg/20 mg combination of MC-1/lisonopril reduced MDASBP by 12 mmHg
compared to baseline (p=0.0001) and to 7.5 mmHg for lisonopril alone (p=0.13). The results were encouraging
enough for the company to decide to push the product into later stages of development.
We expect this therapeutic category to grow to US$32 billion by 2010, driven largely by demographic shifts
which highlight the increasing prevalence of metabolic diseases. Treatment options in this market include
angiotensin receptor blockers, diuretics and beta blockers. This is a highly competitive market with a multitude
of generic options; a product will have to show a significant benefit in terms of efficacy, safety, or convenience
to be successful. Hence, we remain cautiously optimistic about the prospect of this product. The
company will, in our view, have to push the product into later stages of clinical development before it can be
effectively partnered.
Compound Company Description Development Phase
Avandia(rosiglitazone) GSK Assessment of IRI following 8 weeks of rosiglitazone
treatment in patients with metabolic disease; Expected
completion in 2007
Phase II
Lipotor (atorvastatin) Merck Assessment of IRI following 3 day treatment with
atorvastating 80 mg daily; Expected completion in 2007
Phase IV
Angiomax (bivalirudin) Medicines Company Evaluate use of Angiomax in patients with ACS prior to PCI Phase III
Reprieve Radiant Medical Endovascular therapeutic cooling technology; 225 patient
trial in patients with PCI
Phase II/III
TP-10 Avant Immunotherapeutics Complement inhibitor Phase II completed
FX06 Fibrex Medical Fibrin derived peptide; 220 patient trial in PCI patients
KAI9803 Kai Pharma Delta-PKC inhibitor; Phase I

Discovery-Stage Compounds
MC5422 anti-ischemia program. This program revolves around modifying MC-1 and creating mimetics to
further address ischemic and reperfusion injury.
MC-45308 antithrombotics program. Preliminary results have shown significant potential for the lead
drug candidate in this program, MC-45308, in preventing blood clots. The compound has demonstrated both
anti-platelet and anti-coagulant effects, which could make MC-45308 a major player in the management
strategy of cardiovascular diseases such as Myocardial Infarction (MI), stroke, Pulmonary Emboli (PE) and
Peripheral Arterial Disease (PAD). A drug of this type currently is non-existent within the antithrombotic marketplace.
Management
According to the company:
Albert D. Friesen, Ph.D., president and CEO, holds a Ph.D. in Protein Chemistry from the University of
Manitoba. As the first full-time employee and president of the Winnipeg Rh Institute, he oversaw the development
and initial pharmaceutical approval of WinRho. Dr. Friesen has also been instrumental in founding
several health industry companies including Novopharm Biotech Inc. (now Viventia Biotech Inc.), Genesys
Pharma Inc., and KAM Scientific Inc.
Jan-Ake Westin, M.Sc., VP, clinical development, has worked as a managing director at two of Canada’s
leading CROs — i3 Research and Innovus. In this capacity he has overseen the management of numerous
large cardiovascular clinical trials. Mr. Westin spent more than 20 years with Astra Pharma Inc., holding such
positions as international clinical research manager and senior clinical research scientist. Following this, Mr.
Westin proceeded to senior leadership positions with Pharmacia & Upjohn Inc. and Pfizer/Pharmacia Corp.,
where he served as director of clinical operations and director of clinical outsourcing, respectively. Mr. Westin
received his M.Sc. (Social Pharmacy) from the University of Uppsala in Sweden.
Derek G. Reimer, CA, CFO, came to Medicure from Deloitte & Touche LLP where he served as a senior
manager in the Assurance and Advisory Services group. In this role, Mr. Reimer dealt mainly with major corporate
clients, including several TSX 100 companies, providing advice regarding complex accounting, regulatory,
and compliance issues. His previous experience includes several years providing international accounting
services to clients exclusively in the financial services industry. Mr. Reimer is a chartered accountant who
also holds a Bachelor of Commerce (Hons.) degree in accounting from the University of Manitoba. Mr. Reimer
is responsible for managing financial systems, programs, and processes to ensure the successful accomplishment
of Medicure's business objectives.
Valuation and Rating
We are valuing the company on a modified sum-of-the parts basis.
We are projecting that the company can re-grow the AGGRASTAT brand to C23 million in three years. We are
opting to stay on the conservative side of the estimates because the company is inherently relying on offlabel
use to drive AGGRASTAT’s growth. We value this franchise at a multiple of 3x sales. We assume a gross
margin of 90% for this product.
For MC-1, we are using a risk-adjusted probability model of success. We are conservatively assuming a
CY2009 launch using a co-promotion model in which Medicure earns 40% of the revenue generated by the
partnership/joint venture in the United States. We are assuming 30% market penetration in the first year,
which we believe is reasonable given that there is no product in the market for use as a cardioprotectant. We
are pricing MC-1 at US$750 per treatment, which seems comparable to other therapeutics used in a cardioMERRIMAN
CURHAN
FORD
GROW WITH US SM
April 17, 2007 12
Cardiology
Medicure, Inc. Buy
vascular surgery setting. We are also assuming a probability of 60% success to the trial, despite the fact that
it is a pivotal study being conducted under an SPA.
We believe that good Phase III results for MC-1 in IRI should lead to a partnership that targets the use of
MC-1 in PCI. Hence, we include in our valuation model the impact of milestone payments (US$15 million upfront,
US$35 million in development milestones, another US$40 million for commercialization milestones) as
well as a royalty-based revenue stream. In order to remain conservative, we model a 20% probability of success
since we view this aspect of the model rather dependent on MC-1’s performance in the IRI indication.
At the time of this report’s publication, the company had cash and equivalents of approximately C$47 million.
We believe this is enough to fund the company’s activities until the end of the pivotal U.S. Phase III trial. The
company may have to access the capital markets at least one time prior to commercializing the product.
Based on these assumptions, we believe the stock can trade toward the US$2.00-2.20 level in 12 months.
We are therefore we are initiating coverage with a Buy rating.
Medicure Valuation Model (in US$)
Source: MCF & Co.
Key Risks
Medicure may be unsuccessful in marketing AGGRASTAT. The company acquired AGGRASTAT on the
assumption that a lack of sales and marketing efforts are the primary reason that product sales faltered
since 2003. The lack of an effective and continuous marketing campaign for the product in the last few years
prior to the acquisition may have made the brand “stale” in the minds of interventional cardiologists. Despite
the product’s superior performance in diabetics, it may be difficult to overcome the product’s recent track
record.
MC-1 may fail its pivotal phase III trial. At least half of the company’s valuation rests on MC-1. While
the data from MEND-CABG 1 are encouraging, it was only through a retrospective analysis of the data that
led to the decision to redefine MI as CK-MB >=100. We are comforted that the company has reached an
agreement with the FDA regarding this issue, and that the agency had previously allowed Alexion to use the
same definition of MI in the company’s clinical trials for pexeluzimab.
Sales Roy. MCU Launch Year PV Sales Prob. Weighted Per Sh.
Product Indication Partner Ph. ($M) % Rev. ($M) Year Used Pds Rate ($M) Mult. (%) Value ($) Value ($)
AGGRASTAT ACS None Marketed 13 100% 13 2006 2008 0 10% 13 2 100% 26 0.23
MC-1 Cardioprotection None Phase III 185 40% 74 2009 2012 4 10% 51 4 60% 121 1.08
PCI-Upfront None 15 100% 15 2009 2009 1 10% 14 1 20% 3 0.02
PCI-Development None 35 100% 35 2010 2010 2 10% 29 1 20% 6 0.05
PC-Commcerial None 40 100% 40 2012 2012 4 10% 27 1 20% 5 0.05
PCI-Sales None 750 18% 135 2011 2016 8 10% 63 5 20% 63 0.56
MC-4232 Hypertension None Phase II
@ Yearend
Cash 22.3 19 0.17
112.0 $243 $2.17
Discount
Current 12-Mnt Burn
Not considered in valuation
40.8
Current shares outstanding (M) 12-18 Month Valuation
MERRIMAN
CURHAN
FORD
GROW WITH US SM
April 17, 2007 13
Cardiology
Medicure, Inc. Buy
Other Public Companies Mentioned in This Report
Avant Immunotherapeutics (AVNC, $2.33, Not Rated)
Alexion Pharmaceuticals Inc. (ALXN $44.46, Not Rated)
Bristol-Myers Squibb (BMY $27.99, Not Rated)
Eli Lilly & Co. (LLY $56.76, Not Rated)
GlaxoSmithKline plc (GSK $57.97, Not Rated)
Merck & Co., Inc. (MRK $49.86, Not Rated)
MGI Pharma Inc. (MOGN $23.69, Not Rated)
Millenium Pharmaceuticals Inc. (MLNM $11.44, Not Rated)
The Medicines Company (MDCO, $26.11, Not Rated)
Sanofi Aventis SA (SNY $45.56, Not Rated)
MERRIMAN
CURHAN
FORD
GROW WITH US SM
April 17, 2007 14
Cardiology
Medicure, Inc. Buy
Jose J Haresco, Ph.D.
Senior Vice President
(415) 248-5629
jharesco@mcfco.com
Source: MCF & Co.; company filings
Medicure, Inc.
Quarterly Income Statement
(In CAN$)
2008 2009 2010
8/31/2005 11/30/2005 2/28/2006 5/31/2006 FY 8/31/2006 11/30/2006 2/28/2007 5/31/2007 FY 5/31/2008 5/31/2009 5/31/2010
Revenue
AGGRASTAT $ - $ - $ - $ - $ - $ 2 80 $ 1 ,419.0 $ 2 ,552 $ 3 ,500 $ 7 ,751 $ 1 3,000 $ 1 8,000 $ 2 3,000
MC-1 $ 1 7,000 $ 4 0,000
MC-1 Milestones
Cost of Goods - - - - - 2 8 5 4.3 1 77 3 50 6 09 1 ,300 1 ,800 2 ,300
Gross Profit - - - - - 2 52 1 ,364.7 2 ,375 3 ,150 7 ,142 1 1,700 3 3,200 6 0,700
Operating Expenses
R&D 3 ,297 3 ,010 1 ,881 2 ,031 1 0,219 2 ,783 3 ,816.0 6 ,518 7 ,000 2 0,117 2 5,000 1 2,500 1 3,000
Amortization 5 82.9 7 74 7 80 2 ,909 1 ,800 1 ,800 1 ,800
Investments Tax
SG&A 5 37 6 36 8 61 8 24 2 ,858 1 ,160 2 ,658.0 3 ,425 3 ,700 1 0,943 1 5,000 2 5,000 2 7,000
Total Operating Expenses 3 ,834 3 ,646 2 ,742 2 ,855 1 3,077 3 ,943 7 ,056.9 1 0,717 1 1,480 3 3,196 4 1,800 3 9,300 4 1,800
Operating Income (3,834) (3,646) (2,742) (2,855) (13,077) (3,691) (5,692.2) (8,342) (8,330) (26,055) (30,100) (6,100) 1 8,900
EBITDA (3,834) (3,646) (2,742) (2,855) (13,077) (3,691) (5,692.2) (8,342) (8,330) (26,055) (30,100) (6,100) 1 8,900
Interest & Other Expense (790.0) (462) (600) (1,852) 1 ,600 1 ,400
Interest Income 2 5 3 5 6 1 1 79 3 00 2 90 3 90.0 4 67 4 40 1 ,587 1 ,400 2 ,000 2 ,100
Pretax Income (3,809) (3,611) (2,681) (2,676) (12,777) (3,401) (6,092.2) (8,365) (8,490) (26,349) (27,100) (2,700) 2 1,000
Taxes - - - - - - - - - - - -
Net Income $ (3,809) $ (3,611) $ (2,681) $ (2,676) $ (12,777) $ (3,401) $ (6,092) $ (8,365) $ (8,490) $ (26,349) $ (27,100) $ (2,700) $ 21,000
EPS $ (0.05) $ (0.05) $ (0.03) $ (0.03) $ (0.16) $ (0.04) $ (0.06) $ (0.08) $ (0.08) $ (0.24) $ (0.24) $ (0.02) 0.17
Weighted Average 8 0,000 8 0,000 8 0,000 8 0,000 8 0,000 9 2,200 9 6,200 1 11,000 1 12,000 1 12,000 1 13,000 1 25,000 1 26,000
Margins
Cost of Goods Sold NA NA NA NA NA NA NA NA NA NA 10.0% 10.0% 10.0%
Gross Margin NA NA NA NA NA NA NA NA NA NA 90.0% 184.4% 263.9%
SG&A NA NA NA NA NA NA NA NA NA NA 192.3% 69.4% 56.5%
Research & Development NA NA NA NA NA NA NA NA NA NA 115.4% 138.9% 37.1%
Operating Expenses NA NA NA NA NA NA NA NA NA NA 321.5% 218.3% 181.7%
Operating Income NA NA NA NA NA NA NA NA NA NA -231.5% -33.9% 82.2%
Net Income, net of taxes NA NA NA NA NA NA NA NA NA NA -208.5% -15.0% 91.3%
2006 FY2007
MERRIMAN
CURHAN
FORD
GROW WITH US SM
April 17, 2007 15
Cardiology
Medicure, Inc. Buy
Jose J Haresco, Ph.D.
Senior Vice President
(415) 248-5629
jharesco@mcfco.com
Medicure, Inc.
Balance Sheet
(In CAN$)
Source: MCF & Co.; company filings
2/28/2007 5/31/2006
Assets
Current assets
Cash and cash equivalents C$ 43,423 C$ 3 4,920
Accounts recievable 3,287 4 58
Inventories 706
Research advance 200 2 00
Prepaid expense 1,282 2 63
48,898 3 5,842
Property and equipment 133 5 1
Intangible assets 23,922 2 ,922
Defered debt issue expenses
72,953 3 8,814
Liabilities and Shareholders Equity
Current liabilities
Accounts payable and accrued liabilities C$ 6,882 C$ 1 ,644
Current portion of long-term debt 5,054
11,936 1 ,644
Long-term debt 13,476
Shareholder's equity
Capital stock 109,035 8 1,227
Contributed surplus 2,754 2 ,071
Deficit (63,831) (46,128)
47,957 3 7,170
C$ 73,368 C$ 3 8,814
MERRIMAN
CURHAN
FORD
GROW WITH US SM
April 17, 2007 16
Cardiology
Medicure, Inc. Buy
This research has been prepared by Merriman Curhan Ford & Co, a wholly owned subsidiary of MCF Corp. Some companies
Merriman Curhan Ford & Co. follows are emerging growth companies whose securities typically involve a higher degree of risk and
more volatility than the securities of more established companies.
The securities discussed in Merriman Curhan Ford & Co. research reports may be unsuitable for some investors depending on their
specific investment objectives, financial status, risk profile, or particular needs. Investors should consider this report as only a single
factor in making their investment decisions and should not rely solely on this report in evaluating whether or not to buy or sell the securities
of the subject company.
Regulation Analyst Certification (“Reg. AC”)
All of the views expressed in this research report accurately reflect the research analyst’s personal views about any and all of the
subject securities or issuers. No part of the research analyst’s compensation was, is, or will be, directly or indirectly, related to the
specific recommendations or views expressed by the research analyst in the subject company of this research report. Research analysts
are not compensated for revenue generated by the firm’s investment banking activities.
Specific Disclosures
- MCF & Co. has not received compensation for investment banking services within the last 12 months, and does not expect to receive or
intend to seek compensation for investment banking services in the next three months, from Millennium Pharmaceuticals Inc. or Medicure
Inc.
- Within the last 12 months MCF & Co. has not managed or co-managed a public offering for Millennium Pharmaceuticals Inc., or Medicure
Inc.
- MCF & Co. makes a market in MLNM and as such buys and sells from customers on a principal basis. MCF & Co. does not make a market
in MCU.
- Neither Jose Haresco nor a member of his household owns shares of MCU.
- Neither MCF & Co. nor its officers, principals, employees, or owners own options, rights, or warrants to purchase MLNM or MCU.
- No MCF & Co. employee serves on the board of directors of Millennium Pharmaceuticals Inc. or Medicure Inc.
- Neither Jose Haresco nor a member of his household serves on the board of directors of Medicure Inc.
- Neither MCF & Co. nor its affiliates beneficially owns 1% or more of an equity security of Millennium Pharmaceuticals Inc. or Medicure Inc.
Key to Investment Rankings (expected total share price return inclusive of dividend reinvestment, if applicable)
MCF & Co. archives and reviews outgoing and incoming email. Such may be produced at the request of regulators. Sender accepts
no liability for any errors or omissions arising as a result of transmission. Use by other than intended recipients is prohibited.
The information contained herein is based on information obtained from sources believed to be reliable but is neither all-inclusive nor
guaranteed by Merriman Curhan Ford & Co. No independent verification has been made as to the accuracy or completeness of the
information. Opinions, if any, reflect our judgment at the time the report is first published and are subject to change without notice.
Merriman Curhan Ford & Co. does not undertake to advise you of changes in its opinion or information.
Member NASD / SIPC. Copyright © 2007. All rights reserved. Additional information supporting the statements in this report is available
upon request.
Rating Percent of
Universe
No. of
Stocks Description
Percent of companies under research
coverage from which MCF & Co. received
compensation for investment banking
services provided in the previous 12 months
or expects to receive or intends to seek in
the next three months
Buy 73% 131 MCF & Co. expects the stock price to appreciate 10% or
more over the next 12 months. Initiate or increase position. 15%
Neutral 25% 46 MCF & Co believes the stock price is fairly valued at current
levels. Maintain position or take no action. 2%
Sell 2% 4 MCF & Co. expects the stock price to depreciate over the
next 12 months. Sell or decrease position. 0%




Public Reply | Private Reply | Keep | Last Read Replies (1) | Next 10 | Previous | Next

Add Board Mark Report TOS Violation

I hope no one minds but I asked to take over the job as moderator to update the board. If anyone has any comments or suggestions about the board I would like to hear them.

Medicure, Inc. (MCU)

An Undervalued Late-Stage Cardiovascular Biotechnology Company; Initiating Coverage at Buy

Initiating Coverage at Buy
Price: $1.20
Market Cap (M): $139.4M

FY07 Revenue Estimate (M):
Previous: N/A
Current: C$7.8

FY07 EPS Estimate:
Previous: N/A
Current: (C$0.24)

FY08 Revenue Estimate (M):
Previous: N/A
Current: C$13.0

FY08 EPS Estimate:
Previous: N/A
Current: (C$0.24)

· Unmet need for a cardioprotectant. Ischemic reperfusion injury (IRI) is thought to be responsible for the myocardial damage that can occur following a coronary artery bypass graft (CABG). IRI is associated with a high risk of death, MI, heart failure, arrhythmia, renal insufficiency, and stroke after CABG surgery. All of these can add up to a 20% incidence of major vascular events following CABG surgery.

· Unique technology. We believe MC-1 blocks the signaling cascade that ultimately causes ischemic reperfusion injury. It is has shown very promising results in multiple Phase II trials, and is currently in the midst of a pivotal Phase III trial. This trial is being conducted under the auspices of an SPA agreement with the FDA, which reduces the regulatory risk of the product, in our view. The upside to this product may be its eventual use in percutaneous coronary intervention (PCI). We believe this product has a high probability of being partnered within the next three years.

· AGGRASTAT is an undervalued asset, in our view. Medicure acquired AGGRASTAT in late 2006 from MGI Pharma (MOGN $23.91, Not Rated). Despite offering better efficacy in diabetics at a lower cost, AGGRASTAT sales have floundered due to lack of a coherent commercialization effort. We believe Medicure’s re-growth of this brand can generate solid revenues and provide a commercial platform for the eventual launch of MC-1.

· Significant potential market opportunities. AGGRASTAT operates in the US$500 million U.S. platelet inhibitor market. We believe that the market for MC-1 in the CABG setting is worth US$185 million in the U.S. alone. The use of MC-1 in coronary artery stenting procedures provides another US$750 million in potential market opportunities.

· Initiating coverage at Buy. We are valuing the company on a modified sum-of-the-parts basis. We are projecting that the company will re-grow the AGGRASTAT brand to C$23 million in three years. For MC-1, we are using a risk-adjusted probability model of success. We are conservatively assuming a CY2009 launch using a co-promotion model in which Medicure earns 40% of the revenue generated by the partnership/joint venture in the U.S. We are assuming 30% penetration of the market in the first year, which we believe is reasonable given that there is no product in the market for use as a cardioprotectant. We are also only assuming a probability of 60% success to the trial, despite the fact that it is a pivotal study being conducted under an SPA. We believe the stock can trade toward the US$2.00-2.20 in 12 months, and we are therefore initiating coverage with a Buy rating.

-- Jose J. Haresco, Ph.D. (415) 248-5629 jharesco@mcfco.com

* Yesterday Medicure Inc. reported 3Q07 EPS of ($0.08) and
indicated
that its pivotal Phase III for MC-1 is on track to complete
enrollment in November. We expect Phase III results from MC-1 in
1Q08. Medicure reported 3Q07 Aggrastat revenues of $2.52M. We
find
it encouraging that Aggrastat sales are up nicely
quarter-over-quarter. Our long-term estimates, primarily driven
by
MC-1, remain unchanged. We have made minor changes to our
near-term estimates based on a better understanding of near-term
cost drivers.

* Approximately 90% of Medicure's R&D expenses are attributable to
MC1. There were significant up-front costs in starting the MC-1
trial, which resulted in higher than normal R&D in Q3. R&D is
likely to be high over the next few quarters as Medicure
continues
to enroll patients, after which we believe it is likely to
decline
from current levels.

* Due to its poor brand image in the US, we give very little credit
to Aggrastat. However, we believe its brand image could be
improved with additional data from head-to-head studies against
competitors such as ReoPro and Integrillin. We were pleasantly
surprised to hear on the conference call that Merck is running
several large trials to prove equivalence of Aggrastat. Positive
results from these trials could lower the risk for Medicure in
running similar trials in the US, which could eventually lead to
substantial sales growth for Aggrastat, in our view. We believe
that results from these trials could become available as soon as
at ACC next year. We are not altering our current Aggrastat
forecast of no change in sales from 2007 to 2012.

* Management clarified that the p-value needed for success in the
Phase III trial was close to 0.05 but lower than that, and at the
same time much higher than 0.01. We believe this is a good
revelation because there have been rumors that the statistical
barrier for the Phase III trial is very high owing to the
substantially low p-value that is required to be met.

http://www.monty.com/please-see/disclaimer3.htm

In the Stent Era, Heart Bypasses Get a New Look


from the NY Times
By BARNABY J. FEDER
After more than a decade-long decline, is heart bypass surgery poised for a comeback?

Some doctors say it may be time to give bypass operations a second look. They include even some cardiologists who specialize in the far more popular alternative — using stents to keep coronary arteries open.

No one is predicting a sudden surge back to bypass, which is still a far more invasive and initially riskier way to treat plaque-clogged heart arteries, a condition that afflicts millions of Americans.

But in light of new safety concerns over the long-term risks of stents, as well as accumulating data indicating that the sickest heart patients may live longer if they receive bypass surgery instead, some well-known stent specialists say the pendulum may have swung too far away from bypass surgery.

“We as cardiologists have probably pressed forward on stent technology a little faster than we should have,” said Dr. Kirk Garratt, the director of research into stents and related heart therapies at Lenox Hill Hospital in New York, one of the nation’s leading stenting centers.

It is a remarkable acknowledgment, considering the medical and financial stakes in play. In the last decade, the number of bypass surgeries in this country has fallen by a third — to about 365,000 last year. Meanwhile, the number of patients receiving stents has soared, to nearly a million in 2006.

To some extent, the stent preference has been propelled by patients themselves, who have an understandable aversion to major surgery.

“Most of the time that I recommend bypass surgery, the patient begs me to put in stents instead,” said Dr. Ralph Brindis, senior cardiovascular adviser for the network of Kaiser Permanente hospitals and clinics in Northern California.

But stents are also big business, with powerful advocates like Boston Scientific and Johnson & Johnson, whose stent sales totaled about $2.9 billion last year. They, along with competitors trying to catch up, have invested heavily in expanding the use of stents.

And cardiologists, the specialists who are most likely to diagnose artery disease, are in many cases also the doctors who implant stents. Their judgment heavily influences which patients get referred to surgeons.

Meanwhile, as Medicare and other insurers have curbed their payments for bypass surgeries, the cost of stenting has risen with the introduction of newer devices. Surgery and stent procedures are now comparably priced for patients with multiple blockages — an average of around $30,000, according to the American College of Cardiology and the American Heart Association. Both procedures are generally covered by insurers.

As a result of these forces, surgeons, once the kings of the cardiac ward, have seen their annual incomes dwindle. They averaged $425,000 last year, down from $1.02 million in 1990, after adjusting for inflation, according to John O. Goodman, a leading consultant to cardiovascular doctors.

Meanwhile, Mr. Goodman said, the average income of an interventional cardiologist, as a stent specialist is known, has risen to $550,000 from an inflation-adjusted $392,000 in 1990.

But Mr. Goodman says he expects the number of bypass surgeries to begin rising this year, although he declines to forecast by how much.

What has changed most recently in the stents-versus-surgery calculus is new evidence that surfaced in clinical trials last year. The data disclosed a previously undetected risk with stents, which are tiny mesh cylinders that are placed in arteries via filament-thin catheters threaded from a tiny incision in the thigh.

The new evidence showed that patients receiving the most popular form of stents — ones coated with drugs to reduce the likelihood that the artery will close again — have a slight risk of forming potentially fatal blood clots in the stents long after they have been implanted.

That changed the cost-benefit calculus of stents versus surgery in cases where patients have multiple blockages in two or more arteries or have other complications.

Bypass surgery is the recommended treatment for such patients, according to the guidelines of the American Heart Association and the American College of Cardiology. But some doctors say too many patients never hear about those recommendations from their cardiologists.

A joint committee of the heart association and cardiology society expects to release new guidelines within the next month that could clarify the proper boundary between stenting and surgery, according to Dr. Sydney C. Smith Jr., the head of the committee.

One controversial factor in such assessments is the accumulating data suggesting that surgery may help the sickest heart patients live longer.

Studies tracking long-term results among patients around the nation have prompted some surgeons to argue that thousands of people with blockages in multiple arteries may be dying months or even years prematurely because they receive stents instead of surgery.

Dr. Robert A. Guyton, the chief of cardiothoracic surgery at the Emory University School of Medicine in Atlanta, argues that as many as 200,000 such patients who get stents each year should be having bypass surgery instead. He bases that conclusion on studies using data from nearly 40,000 patient cases in New England and New York and at Duke University.

Stenting and bypass surgery are both meant to relieve symptoms like chest pain and shortness of breath, which are caused by a buildup of arterial plaque that may eventually lead to heart attacks and gradual heart failure.

Neither stents nor bypass surgery can halt the buildup of plaque. But surgery, by bypassing an entire section of diseased artery with a vessel taken from elsewhere in the body, can restore more blood flow and the benefits may last longer.

And while bypass surgery still typically involves the trauma of sawing through the breastbone to open the chest, the operation is getting gentler. Blood vessels for grafting can be harvested from arms and legs through much smaller incisions than in the past, for example.

And about 20 percent of the operations no longer require stopping the heart and attaching patients to an external pump, thus eliminating a step believed to increase the risk of strokes in the sickest patients. Some bypasses now can even be performed using a robotic tool through small incisions between the ribs.

Most of the debate over stents versus surgery focuses on complex patients like Edgardo Hilario, 59, a Kmart shelf stocker from Spotswood, N.J. After he was hospitalized last fall with severe chest pain, his doctors found that he had four severe blockages in three arteries.

Mr. Hilario was operated on last month at St. Michael’s Medical Center, a 337-bed teaching and referral hospital in Newark.

The chief of cardiac surgery there is Dr. Mark W. Connolly, a nationally known heart surgeon who was named physician of the year in 2006 by the American Heart Association. Well-regarded among stent specialists, he was invited to speak last fall at their national meeting.

Dr. Connolly, who says he has performed more than 4,000 bypass surgeries, operated on Mr. Hilario and another patient, Francisco Tobio, that day. Both patients probably would have received stents in many other hospitals.

In fact, Mr. Tobio had arrived at St. Michael’s expecting to have a stent procedure performed by Dr. Fayez Shamoon, who had previously treated Mr. Tobio’s wife. But the X-rays of Mr. Tobio’s blockages led Dr. Shamoon to consult with Dr. Connolly, and the two doctors together advised him to have surgery instead.

“Dr. Shamoon put three stents in my wife, so I trusted him,” Mr. Tobio said.

All hospitals expect both cardiologists and surgeons to consult with heart patients when the form of treatment is in question. But with few patients demanding the chance to talk to a surgeon, it is usually up to a cardiologist like Dr. Shamoon to initiate such a meeting.

How often that happens may depend on the degree of respect and collaboration between a hospital’s cardiologists and surgeons, many doctors say.

Another factor, cardiologists say, is the unwillingness of some surgeons to take on complex cases, especially in states like New York and California that now report performance statistics for each doctor.

“They started sending cases back to us because of reporting,” said Dr. Robert Jesse, the top cardiologist for the Veterans Health Administration.

The data suggesting that patients may be suffering as a result of such trends is hardly ironclad. Little of it comes from randomized clinical trials, which are considered the highest level of evidence in medicine. Instead, the pro-bypass case rests mainly on data from registries that track long-term outcomes for every patient treated at a single major hospital or across large regions.

Such registries can offer a more accurate picture of how medicine is really practiced than clinical trials, which focus on preselected patients. But many researchers say that because registry data tends to be collected more haphazardly, it is better at identifying issues for further study than guiding medical practice.

Two major clinical trials now under way will try to directly compare stents and bypass surgery in patients with the most serious forms of artery disease. One trial, sponsored by Boston Scientific, randomly assigns 1,500 patients to either surgery or stenting. The other, sponsored by the National Heart, Lung and Blood Institute, compares stenting to bypass surgery in diabetic patients with multiple coronary blockages.

But the first results, which will come from the Boston Scientific trial, are not expected before the second half of next year. And those near-term results cannot be conclusive about the main stent safety issue now worrying doctors — the long-term risk of potentially fatal blood clots.

Moreover, by the time the trials’ longer-term results are available in 2012, they may have little applicability to medical practice at that time.

Despite the forces now favoring stents, Mr. Goodman, the consultant, says he expects the number of bypass surgeries to begin rising this year. Concerns about stent safety will play a role, he said, but another inducement will come from patients who received stents in recent years and now need follow-up care.

That is what happened to Joseph Gubernick, 72, the chief marketing officer for a division of the Estée Lauder Companies.

Mr. Gubernick had four bare-metal stents implanted in 2000 at Lenox Hill Hospital, after suffering a heart attack on a business trip to Japan. Last fall, when he began feeling symptoms he feared were signs of a new blockage, Mr. Gubernick called Dr. Connolly at St. Michael’s.

A St. Michael’s cardiologist, Dr. Jonathan Goldstein, took X-ray images of the arteries, and told Mr. Gubernick, “The time for stents is past.”

Dr. Connolly did the bypass operation on Dec. 20.

“I’m back at work and feeling terrific,” Mr. Gubernick said on Thursday.

Link to post that is part of extensive thread on Biotech Values board:

http://www.investorshub.com/boards/read_msg.asp?message_id=16754281

Someone who has been down this path before. The ph ii is written up below (and also in JAMA)

http://www.medscape.com/viewarticle/464397

Note that despite the fact that this trial showed a very good result in CKMB and in previous related trials it failed in subsequent, larger, trials.

Other notes - For the above trial the definition of MI is not as simple as CKMB>x although that was one component.

It would be interesting to know whether the drug lowered CKMB in the failed trials - as a measure of how tightly CKMB is coupled with MI/Death.

article posted by big money picks on ymb

The importance of this old article hasn't diminished by time. There aren't many late stage cardiovascular drugs up for licensing. With statins and arbs comming off of patent protection the fact that mc-1 has all of the patents in this area this could lead to a large deal



There will be howls of joy or buckets of tears coming out of drug developer Medicure Inc. over the next few weeks.
The Winnipeg-based company has completed two mid-stage clinical trials with its MC-1 flagship drug and is set to release those results by mid-September and late October. And without enough money in the bank to continue large-scale testing on its own, the company needs a positive outcome to pave the way for a corporate partnership with a drug company to finish development.

Success here could target cardiovascular markets in the billions of dollars, either with MC-1 on its own or in combination with other heart drugs. So far, the company has invested $25-million in developing the drug.

"I'm not superstitious but we've been very fortunate developing MC-1 so far," said Medicure president and chief executive officer Albert Friesen, who is known as the founding father of biotechnology in Manitoba.

Medicure and MC-1 trace their roots to a business lunch in Winnipeg nine years ago. As a trained chemist and CEO of Novopharm Biotech Inc. at the time, Mr. Friesen recalls how impressed he was with University of Manitoba professor Naranjan Dhalla's drug discovery.

"What hit me was the beauty of the molecule, how safe it is and the huge opportunity in cardiovascular disease," he recalls. Mr. Dhalla is now chief scientific officer of Medicure.

Mr. Friesen's claim to fame, however, precedes founding Novopharm, which is now Viventia Biotech Inc. In 1969, he was the first employee of the Winnipeg Rh Institute, which pioneered development of the WinRho drug to protect newborns from anemia, heart failure and brain damage associated with Rh disease.

The drug was approved by Health Canada in 1980. WinRho is also used to treat a clotting disorder known as ITP.

Mr. Friesen also began WinRho's approval process with the U.S. Food and Drug Administration until the institute was acquired in a hostile takeover by Toronto-based Apotex Inc. and became Cangene Inc.

"MC-1 was a chance to take an idea all the way to the marketplace again," he said.

MC-1 is what's called a metabolite of vitamin B6, one of three chemical compounds left over from reactions between the vitamin and enzymes in the body. The metabolite binds naturally with the protein albumin, circulates in the blood and is slowly released in the heart and other organs.

What impresses analysts about MC-1 is that it is a new drug class, with the potential to reduce damage to heart tissue.

"Our belief is that Medicure may be able to build a business solely on using MC-1 in combination with other therapies," National Bank Financial analyst André Uddin said in a recent research report.

After posting positive results in an earlier mid-stage study with patients undergoing an angioplasty procedure, Medicure combined MC-1 with an angiotensin-converting enzyme (ACE) inhibitor, which is used to treat high blood pressure. The combined therapy, known as MC-4232, was then used to test 120 diabetic patients with hypertension to see if it would reduce blood pressure, triglycerides and blood glucose levels. Those study results are set to be released in the next few weeks.

Medicure has at least three other combination drugs in early research for heart disease.

In late October, the company will learn how MC-1 performed on its own with 900 patients undergoing coronary bypass surgery. The Phase II study is not designed to show statistical significance, which could make investors skittish, but rather a trend toward reducing heart attacks and strokes in the first 30 days after surgery.

If we can show a reduction of 15 to 25 per cent in clinical events, it would be a home run," Mr. Friesen said. "If we succeed, I believe we have a high probability to repeat in a pivotal Phase III study."

He said Medicure is in "active discussions" to team up with a large drug company specializing in cardiovascular disease and mid-sized specialty drug companies to take MC-1 into late-stage clinical testing, which could require several thousand patients.

"When I started Medicure, I thought it would take 10 to 13 years to develop MC-1 and we're still on schedule."

new investors from the recent financing

remember there was no discount and warrant coverage was only 20 percent

Optimum Small Cap Growth 444,084 444,084 0.37%
Wanger US Smaller Companies 1,776,120 1,776,120 1.48%
Wanger US Small Cap 4,428,360 4,428,360 3.69%
Columbia Acorn USA 4,428,360 4,428,360 3.69%
Federated Kaufmann Small Cap Fund, a Portfolio of Equity Funds 1,206,332 1,206,332 1.00%
American Skandia Trust Federated Aggressive Growth Portfolio 639,822 639,822 0.53%
Nite Capital LP 461,538 846,154 0.38%
ProMed Partners, L.P. 304,632 304,632 0.25%
ProMed Partners II, L.P. 14,442 14,442 0.01%
ProMed Offshore Fund, Ltd. 50,166 50,166 0.04%
ProMed Offshore Fund II, Ltd. 1,015,380 1,015,380 0.85%
Rockmore Investment Master Fund Limited 461,538 461,538 0.38%
Sigma Capital Associates, LLC(3) 1,200,000 1,400,000 1.17%
WHI Growth Fund Q.P., L.P. 1,846,152 1846,152 1.54%
Panacea Fund, LLC 461,544 561,544 0.47%
Monsun AS 600,000 0 0%
Lars H. Hoie 4,569,182 4,769,182 3.97%

link to Medicure analyst date

http://phx.corporate-ir.net/phoenix.zhtml?c=108925&p=irol-EventDetails&EventId=1411105

MCU - MEDICURE INC (AMEX)
This is from Bar Chart
Date Open High Low Last Change Volume % Change
03/10/06 1.70 1.84 1.70 1.79 +0.11 430700 +6.55%


Composite Indicator
Trend Spotter TM Buy

Short Term Indicators
7 Day Average Directional Indicator Buy
10 - 8 Day Moving Average Hilo Channel Buy
20 Day Moving Average vs Price Buy
20 - 50 Day MACD Oscillator Buy
20 Day Bollinger Bands Buy

Short Term Indicators Average: 100% - Buy
20-Day Average Volume - 93660

Medium Term Indicators
40 Day Commodity Channel Index Buy
50 Day Moving Average vs Price Buy
20 - 100 Day MACD Oscillator Buy
50 Day Parabolic Time/Price Buy

Medium Term Indicators Average: 100% - Buy
50-Day Average Volume - 103516

Long Term Indicators
60 Day Commodity Channel Index Buy
100 Day Moving Average vs Price Buy
50 - 100 Day MACD Oscillator Buy

Long Term Indicators Average: 100% - Buy
100-Day Average Volume - 131406

Overall Average: 100% - Buy

Price Support Pivot Point Resistance

1.79 1.64 1.78 1.92




Click on the indicator for a graphical interpretation of the result
or visit the Learning Center for more information on the studies

Medicure to Present at BIO CEO & Investor Conference
Medicure Inc. (TSX:MPH)(AMEX:MCU), a cardiovascular drug discovery and development company, today announced that it will be presenting at the upcoming BIO CEO & Investor Conference. BIO CEO will be held on February 14th & 15th, 2006 at the Waldorf Astoria Hotel in New York City.

Medicure's President & CEO, Albert D. Friesen PhD, has been invited to participate and present in a Diabetes Focus Session panel titled "New Hope for Diabetes Patients". The Focus Session will be held Tuesday, February 14, 2006 at 4:00PM Eastern in the East Foyer room. The panel, consisting of leading biotechnology and pharmaceutical executives, will discuss clinical and therapeutic developments in the area of diabetes. Dr. Friesen will focus on Medicure's novel combination product MC-4232 and its role in treating the multiple risk factors in patients with diabetes.

Dr. Friesen will also be delivering a corporate presentation on Wednesday, February 15, 2006 at 3:30PM Eastern in the Park Avenue Suite Center/North room. The presentation will be webcast live and archived on the Medicure website at www.medicure.com.

The 8th Annual BIO CEO & Investor Conference will provide a forum where senior biotechnology executives, institutional investors, industry analysts, venture capitalists, investment bankers and other industry experts will have the opportunity to shape the future investment landscape of the biotechnology industry. Hosted by the Biotechnology Industry Organization (BIO), the largest industry organization focused exclusively on biotechnology, the BIO CEO & Investor Conference will feature issue-oriented plenary sessions, educational sessions focused on hot technologies, therapeutics and key business issues, company presentations, one-on-one meetings, and networking opportunities.

About Medicure Inc.

Medicure Inc. is a cardiovascular drug discovery and development company focused on developing effective therapeutics for unmet needs in the field of cardiovascular medicine, the largest pharmaceutical market sector. The Company's solid position in this field is supported by the following attributes:

- Cardiovascular focused pipeline: a global market of over US $70 billion

- Two drugs - MC-1 & MC-4232 - advancing to Phase III development

- Four positive Phase II trials completed

- FDA Fast Track designation for MC-1

- Unique products addressing major, inadequately served markets

- Dual action antithrombotic, MC-45308, with positive preclinical results

Medicure also has a medicinal chemistry based Drug Discovery program focused on discovery and advancement of novel small molecule anti-ischemics and antithrombotics towards human clinical studies.

This press release contains forward-looking statements that involve risks, which may cause actual results to differ materially from the statements made, and accordingly may be deemed to be forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The forward-looking statements are made as of the date hereof, and the Company disclaims any intention and has no obligation or responsibility to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.

Medicure Inc. (TSX:MPH) (AMEX:MCU)


Medicure Inc.
Derek Reimer
Chief Financial Officer
(888) 435-2220
Fax: (204) 488-9823
OR
Medicure Inc.
Hogan Mullally
Manager of Investor & Public Relations
(888) 435-2220
Fax: (204) 488-9823
info@medicure.com
www.medicure.com