425 1 d425.htm FILED PURSUANT TO RULE 425 Filed Pursuant to Rule 425

Filed by Nuvelo, Inc. Pursuant to Rule 425

Under the Securities Act of 1933

And Deemed Filed Pursuant to Rule 14a-12

Under the Securities Exchange Act of 1934

Subject Company: ARCA biopharma, Inc.

Commission File No. 000-22873

October 2008

Safe Harbor Statement
This presentation contains “forward-looking statements”
which include, without limitation, statements
regarding the completion of the proposed merger, the merger’s anticipated benefits, timing, progress and
anticipated completion of the combined company’s clinical stage and research programs, including possible
regulatory approval, the potential benefits that patients may experience from the use of the combined
company’s clinical stage compounds, and the cash position of the combined company, which statements are
hereby identified as “forward-looking statements”
for purposes of the safe harbor provided by the Private
Securities Litigation Reform Act of 1995. Such statements are based on our management’s current
expectations and involve risks and uncertainties. Actual results
and performance could differ materially from
those projected in the forward-looking statements as a result of many factors, including, without limitation,
failure to complete the merger in a timely fashion, the risk that Nuvelo’s and ARCA’s business operations will
not be integrated successfully; the combined company’s inability to further identify, develop and achieve
commercial success for products and technologies; the risk that the combined company’s financial
resources will be insufficient to meet the combined company’s business objectives; uncertainties relating to
drug discovery and the regulatory approval process; clinical development processes; enrollment rates for
patients in our clinical trials; changes in relationships with strategic partners and dependence upon strategic
partners for the performance of critical activities under collaborative agreements; and the impact of
competitive products and technological changes. These and other factors are identified and described in
more detail in Nuvelo’s filings with the SEC, including without limitation Nuvelo’s quarterly report on Form
10-Q for the quarter ended June
30, 2008 and subsequent filings. We disclaim any intent or obligation to
update these forward-looking statements
2

Merger Creates Valuable Company
•
Late-stage cardiovascular company
•
Near-term commercial opportunity with filed NDA
•
Attractive portfolio to fuel long-term growth
•
Addressing major market opportunities
•
Experienced cardiovascular leadership
•
Funding expected to be adequate for value-creating
milestones
3

Value-Driving Near-Term Milestones
Milestone
NDA acceptance by FDA
•
Completion of merger
•
Initiate Phase 2 NU172 trial
•
LabCorp PMA submission to FDA
for Gencaro genetic test
•
Anticipated FDA CRAC meeting
•
FDA decision on Gencaro
•
Potential launch of Gencaro
Expected Timing
H2:08
Q408/Q109
Q408/Q109
Q408/Q109
H1:09
PDUFA Date: 5/31/09
H1:10
4

Gencaro™* (bucindolol
hydrochloride) : Personalizing
Heart Failure Treatment
5
* Trade name pending FDA approval

Gencaro:
First Personalized Treatment for Heart Failure
•
Next-generation beta-blocker with unique pharmacology
•
First genetically-targeted cardiovascular drug candidate
–
Companion genetic test being developed by LabCorp
•
Potential to target ~50% of heart failure (HF) patients
–
‘Very Favorable’
genotype is target patient population for
treatment
•
Several significant potential follow-on indications
–
Potential prevention of several forms of cardiac arrhythmias
6

Established, Large Market Opportunity
•
~6 million US patients living with heart failure
–
~550K newly diagnosed patients annually
•
Beta-blockers current standard of care
–
“Beta-blockers should be prescribed to all patients with stable HF
due to reduced LVEF …..”
(ACC/AHA Guidelines 2005)
•
Difficult to determine if therapy is working with current
standard of care
7

Personalized
to Improve Outcomes
•
Personalized medicine designed to:
–
Maximize response
–
Minimize side effects
–
Reduce costs to the health care system
•
Gencaro: Personalized treatment for improved outcomes
–
Common genetic variations predict individual patient response
–
Easy-to-administer accompanying genetic test
8

Partnered with LabCorp
•
Easy-to-administer genetic test
•
Turnaround time for results expected
within 48 hours
•
Test results will identify most favorable
responders
•
510K/PMA track within FDA
–
Coordinated with Gencaro NDA
9

Gencaro Unique Pharmacology
No Class Effect
Compound,
(Device)
Molecular Pharmacologic Properties
1
AR
Blockade
2
AR
Blockade
1
AR
Blockade
3
AR
Effects,
NO 
2c
AR
Modulated
NE
Lowering
1 
Arg/Arg
Inverse
Agonism
Bucindolol
+ + + +
+ + + +
+
Full
agonist
+ + +
++
Carvedilol
+ + + +
+ + +
+ + + +
Antagonist
+
?
Metoprolol
+ + + +
+ +
0
0
0
0
Mild
Vasodilatation
Ideal NE
Lowering
Optimum ß
Blockade
10

Genetic Basis Of Gencaro Response
Mediated through individual genetic variation
“Arg/Arg”
1
389
AR”
Better bucindolol antagonism
-
increased survival
-
reduced hospitalization
Favorable receptor
type
“Gly Variant”
1
389 AR
Standard bucindolol
antagonism
Low function receptor
Adverse when combined with
2c
Del genotypes
1.
1
-AR blockade/
R* inactivation
“WT”
2c
AR”
Tonically inhibits NE release
Mild, ideal NE lowering with
bucindolol
Favorable receptor type when
combined with
1
389 Gly
genotypes
“Deletion Variant”
2c
AR
Less inhibition of NE release
Marked NE lowering with
bucindolol
Adverse receptor type when
combined with
1
389 Gly
genotypes
2. Sympatholysis, via
2
-AR blockade
11

Comparison of Beta-blocker Studies*: US & ROW
-20%
US
COPERNICUS
Carvedilol
n = 482
Bucindolol
n=2708
Metoprolol
n =1071
Bucindolol
(VF
Genotype)
n= 493
Metoprolol
n = 3991
Carvedilol
n = 2289
Trial Name
BEST
MERIT
BEST
MERIT
COPERNICUS
Trial Location
US
US
US
WW
WW
All-cause Mortality
-13%
+5%
-38%
-34%
-35%
CV Mortality
-16%
-4%
-48%
-38%
No Data
Mortality + Cardiac
Transplant
-14%
-43%
-32%
No Data
Mortality & HF
Hospitalizations
-21%
-16%
-35%
-31%
-33%
HF Hospitalizations, TTE
-23%
No Data
-36%
NA
-28%
HF hospitalization days
-24%
No Data
-48%
-36%
-41%
Total MI in HF Patients
-45-47%
No Data
-48%
No Data
No Data
12
*  Not head-to-head studies

BEST: Clinical Responses by Genotypes
*p<0.05; **p<0.007
Endpoint
Very Favorable
Genotype (47%)
Favorable
Genotype (40%)
Unfavorable
Genotype (13%)
AC Mortality (ACM),
Time-to-Event (TTE)
38% *
25%
4%
CV Mortality, (CVM),
TTE
48% *
40%*
11%
HF Progression, TTE
†
34% **
20%
1%
HF Hosp/pt
43% *
16%
26%
HF Hosp days/pt
48% **
17%
19%
†
Composite endpoint consisting of: HF mortality, cardiac transplant, HF hospitalizations,
and HF emergency room visits
13

NDA submission to
the FDA: 7/31/08
Potential FDA
Cardio-Renal
Advisory
Committee 
(CRAC)
meeting
Potential
commercial
launch
PDUFA Date:
5/31/09
FDA
acceptance of
NDA filing:
9/19/08
2008
2009
2010
Gencaro Pathway to Market
LabCorp PMA
submission to the
FDA for
complementary
genetic test
14

Targeted Sales/Marketing
•
Cardiologists initiate and influence beta-blocker
prescriptions
•
Penetrate U.S. market with specialized sales force
•
Unique and desirable offering in large market
–
Expected to be only drug with companion test
to predict response
15

Pricing and Reimbursement
•
Current beta-blocker pricing:
–
Generic products are nominally priced
–
Branded products ranging from $2.44 -
$4.74 /day
(AWP)
•
While majority of patients are Part D eligible, most opt for
supplemental commercial prescription coverage
•
Expected to be on formulary with reasonable pricing
•
Test anticipated to be covered via medical benefit, Part B
•
Potential favorable pharmacoeconomics for Gencaro
16

Attractive portfolio to fuel
long-term growth
17

NU172: Targeting
Major Unmet Need
18
~ 400,000 coronary artery bypass
graft (CABG) procedures annually in
U.S.*
Potential for expansion into other
medical or surgical procedures
•
Heparin anticoagulation
•
Protamine antidote for reversal
once procedure is complete
*American Heart Association
Anticoagulation for Medical/Surgical
Procedures
Large Population
Standard of Care

Ideal Profile for Short-Term
Anticoagulation
19
•
Reduced bleeding risk
during and post
procedure
•
No drug induced
thrombocytopenia
•
Synthetic (no animal
based products)
•
Potent anticoagulation
•
Active against clot
bound thrombin
•
Effective in static blood
•
Predictable dosing
•
Rapid onset
•
Rapid offset without
need for antidote
Administration
Safety
Efficacy

NU172 Proof-of-Concept Achieved
20
•
Favorable safety profile
with no adverse events
•
Dose-dependant
increases in
anticoagulation
•
Anticoagulation
maintained stably
throughout 4-hour
infusion
•
Rapid return toward
baseline upon drug
discontinuation
•
Short plasma half-life
•
2.0mg/kg IV bolus
followed by escalating
infusion doses for up to
4 hours
•
Highest infusion dose:
6.0mg/kg/hr
Phase 1b Results: Rapid and predictable onset and offset of
anticoagulation
Administration
Safety
Efficacy

NU172: Rapid and Predictable
Onset/Offset of Anticoagulation
Phase 1b Results
21
Avg
ACT of Subjects Receiving
2.0 mg/kg bolus + 6 mg/kg/hr 4-hr infusion
0
100
200
300
400
500
0
50
100
150
200
250
300
Time (mins
post bolus)
ACT= 395 at 5 mins
post-bolus
Infusion
Stopped

Value-Driving Near-Term Milestones
Milestone
NDA acceptance by FDA
•
Completion of merger
•
Initiate Phase 2 NU172 trial
•
LabCorp PMA submission to
FDA for Gencaro genetic test
•
Anticipated FDA CRAC meeting
•
FDA decision on Gencaro
•
Potential launch of Gencaro
Expected Timing
H2:08
Q408/Q109
Q408/Q109
Q408/Q109
H1:09
PDUFA Date: 5/31/09
H1:10
22

October 2008

Additional Information and Where to Find It
•
Nuvelo intends to file a registration statement on Form S-4, and a related proxy statement/prospectus, in connection
with the merger. Investors and security holders are urged to read the registration statement on Form S-4 and the
related proxy statement/prospectus when they become available because they will contain important information
about
the
merger
transaction.
Investors
and
security
holders
may
obtain
free
copies
of
these
documents
(when
they
are
available)
and
other
documents
filed
with
the
SEC
at
the
SEC’s
website
at
www.sec.gov.
In
addition,
investors
and security holders may obtain
free copies of the documents filed with the SEC by contacting Nuvelo Investor
Relations at the email address: ir@nuvelo.com or by phone at 650-517-8000.
•
In addition to the registration statement and related proxy statement/prospectus, Nuvelo files annual, quarterly and
special
reports,
proxy
statements
and
other
information
with
the
SEC.
You
may
read
and
copy
any
reports,
statements
or
other
information
filed
by
Nuvelo,
Inc.
at
the
SEC
public
reference
room
at
100
F
Street,
N.E.,
Washington, D.C. 20549. Please call the SEC at 1-800-SEC-0330 for more information. Please call the SEC at 1-800-
SEC-0330 for further information on the public reference room. Nuvelo, Inc.’s filings with the SEC are also available
to
the
public
from
commercial
document-retrieval
services
and
at
SEC’s
website
at
www.sec.gov,
and
from
Investor
Relations at Nuvelo as described above.
•
This communication shall not constitute an offer to sell or the solicitation of an offer to sell or the solicitation of an
offer to buy any securities, nor shall there be any sale of securities in any jurisdiction in which such offer,
solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such
jurisdiction. No offering of securities shall be made except by means of a prospectus meeting the requirements of
Section
10 of the Securities Act of 1933, as amended.
•
Nuvelo, ARCA and their respective directors and executive officers may be deemed to be participants in the
solicitation
of
proxies
from
the
stockholders
of
Nuvelo
in
connection
with
the
merger
transaction.
Information
regarding
the
special
interests
of
these
directors
and
executive
officers
in
the
merger
transaction
will
be
included
in
the
proxy
statement/prospectus
of
described
above.
Additional
information
regarding
the
directors
and
executive
officers
of
Nuvelo
is
also
included
in
Nuvelo’s
proxy
statement
for
its
2008
Annual
Meeting
of
Stockholders
which
was
filed
with
the
SEC
on
April
23,
2008
and
its
Annual
Report
on
Form
10-K
for
the
year
ended
December
31,
2007,
which
was
filed
with
the
SEC
on
March
12,
2008.
These
documents
are
available
as
described
above.