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 mergers anticipated benefits,
timing, progress and anticipated completion of the combined companys
clinical stage and research programs, including possible regulatory
approval, the potential benefits that patients may experience from the use of the combined companys 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
managements 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 Nuvelos and ARCAs business operations will not be integrated successfully; the combined companys inability to further
identify, develop and achieve commercial success for products and
technologies; the risk that the combined companys financial resources
will be insufficient to meet the combined companys 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 Nuvelos filings with the SEC,
including without limitation Nuvelos 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 SECs 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 SECs 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 Nuvelos 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. |