UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): May 8, 2019

 

ARCA biopharma, Inc.

(Exact name of Registrant as Specified in Its Charter)

 

 

Delaware

000-22873

36-3855489

(State or Other Jurisdiction

of Incorporation)

(Commission File Number)

(IRS Employer

Identification No.)

 

 

 

11080 CirclePoint Road, Suite 140, Westminster, CO

 

80020

(Address of Principal Executive Offices)

 

(Zip Code)

Registrant’s Telephone Number, Including Area Code: (720) 940-2200

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instructions A.2. below):

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. 

Securities registered pursuant to Section 12(b) of the Act:

Title of each class

Trading Symbol(s)

Name of each exchange on which registered

Common

ABIO

Nasdaq Capital Market

 

 

 


 

 

Section 2 — Financial Information

 

Item 2.02.

Results of Operations and Financial Condition.

On May 8, 2019, ARCA biopharma, Inc. (“ARCA”) issued a press release reporting financial results for the quarter ended March 31, 2019.  

The press release is attached hereto as Exhibit 99.1, which is furnished under Item 2.02 of this report and shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, regardless of any general incorporation language in such filing.

 

Section 8 — Other Events

 

Item 8.01.

Other Events.

On May 8, 2019, ARCA biopharma, Inc., or ARCA, made a presentation available regarding a business update, which is attached hereto as Exhibit 99.2, and the contents of which are incorporated herein by reference.

Caution Concerning Forward Looking Statements

 

This Current Report on Form 8-K and attached presentation may contain forward-looking statements made in reliance upon the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended.  These statements include, but are not limited to, statements regarding potential future development plans for Gencaro, including our ability to secure sufficient financing to support the anticipated Phase 3 clinical trial of Gencaro, the likelihood that any Phase 3 clinical trial results for Gencaro to satisfy the requirements of ARCA’s Special Protocol Assessment agreement, the expected features and characteristics of Gencaro, including the potential for genetic variations to predict individual patient response to Gencaro or AB171, Gencaro’s potential to treat atrial fibrillation, or AF, future treatment options for patients with AF, the potential for Gencaro to be the first genetically-targeted AF prevention treatment, statements regarding the potential market size of any of ARCA’s product candidates, if approved, statements regarding potential Phase 3 development plans for Gencaro, including the timing and results thereof, the expected features and characteristics of AB171 as a potential genetically-targeted treatment for peripheral arterial disease and for heart failure, or HF, the potential timeline for development of AB171, including any Investigational New Drug, or IND, application submission related thereto, and the ability of ARCA’s financial resources to support its operations through the third quarter of 2019, the sufficiency of ARCA’s current capital to reach certain of its corporate objectives, ARCA’s ability to obtain additional funding when needed or enter into a strategic or other transaction, including its ability to raise sufficient capital to fund any Phase 3 clinical trials for Gencaro and its other operations, the extent to which ARCA’s issued and pending patents may protect its products and technology, the potential of such product candidates to lead to the development of safe or effective therapies, ARCA’s ability to enter into collaborations, ARCA’s ability to maintain listing of its common stock on a national exchange, ARCA’s future operating expenses, ARCA’s future losses, ARCA’s future expenditures, and the sufficiency of ARCA’s cash resources to maintain operations.  These and other factors are identified and described in more detail in ARCA’s filings with the Securities and Exchange Commission, including without limitation ARCA’s annual report on Form 10-K for the year ended December 31, 2018, and subsequent filings. ARCA disclaims any intent or obligation to update these forward-looking statements

Section 9 — Financial Statements and Exhibits

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits.

 

 

 

Exhibit Number

 

Description

 

 

99.1

 

Press Release titled “ARCA biopharma Announces First Quarter 2019 Financial Results and Provides Corporate Update” dated May 8, 2019 .

99.2

 

Investor Presentation titled “ARCA biopharma Pharmacogenetic Precision Medicine for Cardiovascular Diseases” dated May 8, 2019 .

 

 

 

 

 

 


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

Dated: May 8, 2019

 

 

 

 

ARCA biopharma, Inc.

 

(Registrant)

 

 

 

 

By:

/s/ Brian L. Selby

 

 

Name:

Brian L. Selby

 

 

Title:

Vice President, Finance and Chief Accounting Officer

 

 

 

 

Exhibit 99.1

 


 

 

 

ARCA Biopharma announces first quarter 2019 financial results AND Provides CorporatE update

Westminster, CO, May 8, 2019 – ARCA biopharma, Inc. (Nasdaq: ABIO), a biopharmaceutical company applying a precision medicine approach to developing genetically-targeted therapies for cardiovascular diseases, today reported financial results for the quarter ended March 31, 2019 and provided a corporate update.

“In the first part of this year, we continued to make progress on our lead development program Gencaro achieving an agreement with the FDA on our Special Protocol Assessment for the PRECISION-AF Phase 3 clinical trial evaluating Gencaro as potentially the first genetically-targeted treatment for atrial fibrillation,” commented Dr. Michael Bristow, ARCA’s President and Chief Executive Officer.  “Importantly, the GENETIC-AF Phase 2B clinical trial results, which are guiding our Phase 3 development, were accepted and published in JACC: Heart Failure.”

Pipeline Update

Gencaro TM (bucindolol hydrochloride) - a pharmacologically unique beta-blocker and mild vasodilator being developed as a potential genetically-targeted treatment for atrial fibrillation (AF) in patients with heart failure (HF).

 

In February 2019, ARCA received a Special Protocol – Agreement Letter from the U.S. Food and Drug Administration (FDA) on its Special Protocol Assessment (SPA) application for the Phase 3 PRECISION-AF clinical trial.  Subject to securing additional financing, ARCA anticipates initiating PRECISION-AF by the end of 2019.

 

In April 2019, GENETIC-AF Phase 2B clinical trial results were published in the Journal of the American College of Cardiology: Heart Failure in the paper “GENETIC-AF: Bucindolol for the Maintenance of Sinus Rhythm in a Genotype-Defined Heart Failure Population”.

AB171 – a thiol-substituted isosorbide mononitrate being developed as a potential genetically-targeted treatment for heart failure (HF) and peripheral arterial disease (PAD).

 

Chemistry, manufacturing and controls (CMC) activities continued in the first quarter.

 

Subject to securing additional financing, IND-enabling non-clinical studies are anticipated to begin in the second half of 2019, and an IND submission is anticipated in the first half of 2020.

 


 

First Quarter 2019 Summary Financial Results

Cash, cash equivalents and marketable securities were $8.0 million as of March 31, 2019, compared to $6.6 million as of December 31, 2018. ARCA believes that its current cash, cash equivalents and marketable securities will be sufficient to fund its operations, at its projected cost structure, through the end of the third quarter of 2019.

Research and development (R&D) expenses for the three months ended March 31, 2019 were $0.7 million compared to $1.7 million for the corresponding period of 2018.  The $1.1 million decrease in R&D expenses was primarily due to decreased clinical expenses following the completion of the GENETIC-AF clinical trial in 2018.

General and administrative (G&A) expenses for the three months ended March 31, 2019 were $1.1 million similar to $1.1 million in the first quarter of 2018.  The Company expects G&A expenses in 2019 to be consistent with those in 2018 as it maintains administrative activities to support our ongoing operations.

Total operating expenses for the three months ended March 31, 2019 were $1.8 million compared to $2.8 million for the corresponding period of 2018.  The decrease in total operating expenses was primarily due to the decrease in R&D expense due to the completion of the GENETIC-AF clinical trial.

Net loss was $1.7 million, or $1.86 per share, for the first quarter of 2019 compared to $2.7 million, or $3.61 per share, for the first quarter of 2018.

The Company will need to raise additional capital to fund future operations and develop Gencaro or any other product candidates, complete a partnership or other possible strategic transactions.

About ARCA biopharma

ARCA biopharma is dedicated to developing genetically-targeted therapies for cardiovascular diseases through a precision medicine approach to drug development. ARCA’s lead product candidate, Gencaro TM (bucindolol hydrochloride), is an investigational, pharmacologically unique beta-blocker and mild vasodilator being developed for the potential treatment of atrial fibrillation in patients with heart failure. ARCA has identified common genetic variations that it believes predict individual patient response to Gencaro, giving it the potential to be the first genetically-targeted AF prevention treatment. The Gencaro development program has been granted Fast Track designation by FDA. ARCA is also developing AB171, a thiol-substituted isosorbide mononitrate, as a potential genetically-targeted treatment for heart failure and peripheral arterial disease (PAD). For more information, please visit www.arcabio.com or follow the Company on LinkedIn .

 


 

Safe Harbor Statement

This press release contains "forward-looking statements" for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding the ability of ARCA’s financial resources to support its operations through the end of the third quarter of 2019, potential future development plans for Gencaro, the expected features and characteristics of Gencaro or AB171, including the potential for genetic variations to predict individual patient response to Gencaro, Gencaro’s potential to treat AF, AB171’s potential to treat HF or PAD, future treatment options for patients with AF, and the potential for Gencaro to be the first genetically-targeted AF prevention treatment . Such statements are based on 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, the risks and uncertainties associated with: ARCA’s financial resources and whether they will be sufficient to meet its business objectives and operational requirements; ARCA may not be able to raise sufficient capital on acceptable terms, or at all, to continue development of Gencaro or to otherwise continue operations in the future; results of earlier clinical trials may not be confirmed in future trials; the protection and market exclusivity provided by ARCA’s intellectual property; risks related to the drug discovery and the regulatory approval process; and, the impact of competitive products and technological changes.  These and other factors are identified and described in more detail in ARCA’s filings with the Securities and Exchange Commission, including without limitation ARCA’s annual report on Form 10-K for the year ended December 31, 2018, and subsequent filings. ARCA disclaims any intent or obligation to update these forward-looking statements.

 

Investor & Media Contact:

Derek Cole

720.940.2163

derek.cole@arcabio.com

 

(Tables follow)

###


 


 

ARCA BIOPHARMA, INC.

BALANCE SHEET DATA

(in thousands)

(unaudited)

 

 

March 31, 2019

December 31, 2018

Cash and cash equivalents

$8,006

$6,608

Working capital

$7,231

$5,984

Total assets

$8,606

$6,825

Total stockholders’ equity

$7,318

$6,032

 

 

ARCA BIOPHARMA, INC.

STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS

(unaudited)

 

 

Three Months Ended

 

 

 

March 31,

 

 

 

2019

 

 

2018

 

 

 

(in thousands, except share

and per share amounts)

 

 

Costs and expenses:

 

 

 

 

 

 

 

 

Research and development

$

662

 

 

$

1,720

 

 

General and administrative

 

1,119

 

 

 

1,053

 

 

Total costs and expenses

 

1,781

 

 

 

2,773

 

 

Loss from operations

 

(1,781

)

 

 

(2,773

)

 

 

 

 

 

 

 

 

 

 

Interest and other income

 

38

 

 

 

41

 

 

Interest expense

 

(3

)

 

 

(3

)

 

Loss before income taxes

 

(1,746

)

 

 

(2,735

)

 

Income tax benefit

 

82

 

 

 

 

 

Net loss

$

(1,664

)

 

$

(2,735

)

 

 

 

 

 

 

 

 

 

 

Change in unrealized loss on marketable securities

 

 

 

 

2

 

 

Comprehensive loss

$

(1,664

)

 

$

(2,733

)

 

 

 

 

 

 

 

 

 

 

Net loss per share:

 

 

 

 

 

 

 

 

Basic and diluted

$

(1.86

)

 

$

(3.61

)

 

Weighted average shares outstanding:

 

 

 

 

 

 

 

 

Basic and diluted

 

895,970

 

 

 

756,706

 

 

 

 

SLIDE 1

ARCA biopharma Pharmacogenetic Precision Medicine for Cardiovascular Diseases May 2019 Nasdaq: ABIO Exhibit 99.2

SLIDE 2

Safe Harbor Statement This presentation contains "forward-looking statements" for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, potential future development plans for Gencaro, ARCA’s ability to complete any clinical trials, the likelihood for PRECISION-AF results to satisfy the requirements of the U.S. FDA Special Protocol Assessment (SPA) agreement, ARCA's ability to launch any clinical trials, or announce any results therefrom, on or before any particular date, ARCA’s ability to raise sufficient capital to fund the PRECSION-AF trial and its other operations, the expected features and characteristics of Gencaro, including the potential for genetic variations to predict individual patient response to Gencaro, Gencaro’s potential to treat AF and/or HF, future treatment options for patients with AF and/or HF, the potential for Gencaro to be the first genetically-targeted AF prevention treatment, and the potential market opportunity for Gencaro, should it receive regulatory approval. Such statements are based on 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, the risks and uncertainties associated with: ARCA’s financial resources and whether they will be sufficient to meet its business objectives and operational requirements; ARCA may not be able to raise sufficient capital on acceptable terms, or at all, to continue development of Gencaro or to otherwise continue operations in the future; an FDA SPA agreement does not guarantee approval of Gencaro or any other particular outcome from regulatory review; results of earlier clinical trials may not be confirmed in future trials; the protection and market exclusivity provided by ARCA’s intellectual property; risks related to the drug discovery and the regulatory approval process; and, the impact of competitive products and technological changes. These and other factors are identified and described in more detail in ARCA’s filings with the Securities and Exchange Commission, including without limitation ARCA’s annual report on Form 10-K for the year ended December 31, 2018, and subsequent filings. ARCA disclaims any intent or obligation to update these forward-looking statements.

SLIDE 3

Investment Highlights Late stage, genetically-targeted cardiovascular company PRECISION-AF: single pivotal Phase 3 trial for AF in HF│FDA SPA agreement February 2019 Anticipated trial initiation: YE2019│interim data: 3Q2021│topline data: 2Q2022 GencaroTM FDA Fast Track Designation for AF in Genotype-Defined HF Population Large and growing market opportunity for Gencaro Potentially first genetically-targeted cardiovascular therapeutic Significant unmet medical need for AF in HF with no FDA approved treatments Estimated $12.5 billion global atrial fibrillation market by 2020 Gencaro in AF/HF potential annual sales - $500M-$800M in US; similar in EU5 Pharmacogenetic platform with additional cardiovascular programs AB171 – Development for HF, PAD │ IND anticipated mid-2020 Potential third asset – Development for pediatric HF (Orphan Indication) │ In-licensing in progress

SLIDE 4

Experienced Leadership Michael R. Bristow, MD, PhD: President /CEO Thomas Keuer: Chief Operating Officer Chris Ozeroff: General Counsel Brian Selby: VP, Finance & Chief Accounting Officer Debra Marshall, MD, FACC: SVP, Medical Affairs Chris Dufton, PhD: VP, Clinical Development Sharon Perry: Sr Director, Regulatory Affairs & Quality Board of Directors Michael R. Bristow, MD, PhD Robert E. Conway (Chairman) Linda Grais, MD, JD Anders Hove, MD Dan Mitchell Raymond L. Woosley, MD, PhD

SLIDE 5

Genetically-Targeted Cardiovascular Pipeline Research Preclinical Phase 1 Phase 2 Phase 3 GencaroTM (bucindolol hydrochloride) AB171 (PGt targeted mononitrate – vasodilator) Prevention of AF in genotype-defined HF population with mild-moderate LV systolic dysfunction PRECISION-AF │ FDA SPA Feb 2019 │ initiation anticipated: YE2019 │ interim data: 3Q2021 │ topline data: 2Q2022 Peripheral Arterial Disease (PAD) Genetically-targeted population Chronic Heart Failure (CHF) Genetically-targeted population Prevention of AF in genotype-defined HF population with preserved LV systolic function AF Label Expansion Trial

SLIDE 6

Inconsistent Therapeutic Response Across Patients Bristow MR, Pharmacol & Therap 2012; Modified from Spear et al., Trends Mol Med, 2001 Individual variations in response to drugs & drug toxicity are common in clinical and marketed drug settings ~10% of drugs are withdrawn from market post-launch as a result of adverse drug reactions Genetic targeting enables patient selection to potentially deliver higher response rates with fewer side effects b-blockers in HF b-blockers in AF

SLIDE 7

Pharmacogenetics: Precision Medicine Applied to Drug Therapy Our Platform Approach Pharmacogenetic drug development by targeting genetic variation in candidate drug targets, using cardiovascular tissue and cells from an extensive and exclusive human heart tissue bank Identify functionally different and important genetic variants with allele frequency ≥ 10% Screen compounds for variant-specific selective favorable action Generate Phase 1B ® Phase 2 data for pharmacogenetic POC and IP Potential benefits Maximizes potential efficacy and therapeutic index Avoids exposing patients unlikely to benefit Enables smaller clinical development programs Intellectual property (IP) generated later in development process

SLIDE 8

Atrial Fibrillation – A Significant Market Opportunity AF is the most common sustained cardiac arrhythmia Affects ~5.2 million (2015) Americans1 2015 worldwide prevalence of AF was estimated at 33 million2 AF is considered an epidemic cardiovascular disease Based on the rate of increase in incidence in the U.S. and industrialized countries3 Estimated global atrial fibrillation market4 $7.2B in 2015 growing to $12.5B in 2020 ARCA estimate of Gencaro opportunity $500M - $800M peak revenue in US; similar in EU5 1- American Journal of Cardiology 2013: 112: 1142-1147 “Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population; AHA – “Cardiovascular Disease: A Costly Burden for America” (Jan 2017), page 7 2- AHA Statistical Update – Heart and Stroke Stats 2017, p306 3- Journal of the American Medical Association. 2001; 285(18):237 0-2375 4- DelveInsight – “Atrial Fibrillation – Market Insights & Drug Sales Forecast - 2020”, May 2016

SLIDE 9

Atrial Fibrillation in Heart Failure – An Unmet Medical Need No FDA approved drug treatments for this indication Approved antiarrhythmic agents are associated with significant side effects Most are contraindicated or have warnings for HF patients New onset AF markedly worsens HF morbidity & increases mortality β-blockers approved for HF but used off-label for AF Demonstrated only limited efficacy for AF prevention No agents approved for AF or HF have genetically influenced clinical response

SLIDE 10

Atrial Fibrillation and Heart Failure AF HF AF/HF Patient Populations G7 Countries (US, EU5, and Japan) in 2022 LVEF HFlrEF LVEF < 40% HFmrEF 40 ≤ LVEF < 50% HFpEF LVEF ≥ 50% Total HF 5.6M 2.7M 7.6M % with AF 30-50% 35-55% 40-60% Total AF/HF 1.7 - 2.8M 1.0 - 1.5M 3.0 - 4.6M 30-60% of HF patients also have AF1 ~50% of HF patients have optimal genotype No Approved or Effective Therapies for AF or HF HF/AF 1- Decision Resources Group, Heart Failure Epidemiology 2018. 2- Piccini et al. JACC-HF 2019 online ahead of publication. 3- Panikowski P et al. Eur Heart J 2016. *HFlrEF = HF with lower-range ejection fraction2. HFmrEF = HF with mid-range EF3. HFpEF = HF with preserved EF3. Current BBs Approved for HF

SLIDE 11

Potentially the first genetically-targeted atrial fibrillation treatment for patients with heart failure Gencaro

SLIDE 12

Gencaro (bucindolol hydrochloride) Compound β-blocker/vasodilator – well characterized small molecule drug class β-blockers target cardiac myocytes to reduce adverse β1-adrenergic receptor signaling that causes cardiac chamber remodeling Gencaro is only β-blocker with genetically differentiated response IP protection into approximately 2031 in the U.S. and Europe Genotype Specific Response Clinical response differentiated by patient genetic profile Specific β1 adrenergic receptor (AR) polymorphism Optimal genotype is ADRB1 Arg389Arg Present in ~50% of US & EU population World wide rights to companion diagnostic test Rapid low-cost standard test Differentiated MOA Competitive antagonism similar to other β-blockers Sympatholysis – norepinephrine lowering Inverse agonism – inactivation of constitutively active receptors Other β-blockers lack these last 2 properties Extensive Clinical Data Favorable safety profile; over 3,400 HF patients studied 74% reduction in AF onset compared to placebo in patients w/most responsive genotype in prior Phase 3 HF trial P2B – 58% reduction in AF recurrence compared to Toprol-XL in genetically-defined HF population with mild-moderate LV systolic dysfunction Bucindolol

SLIDE 13

Differentiated Response by Genotype Seen in BEST Study1 b1389 Arg/Arg (n = 441; 36 events) Risk reduction 74% Hazard Ratio = 1.01 (0.56 – 1.84) P-value = 0.969 b1389 Gly carriers (n = 484; 44 events) No risk reduction Hazard Ratio = 0.26 (0.12 – 0.57) P-value = 0.0003 b-blocker class 27% average risk reduction in AF onset in ~12,000 patient meta-analysis of Phase 3 HF trials.2 Metoprolol and Carvedilol are not influenced by ADRB1 Arg389Gly3 1- Aleong RG et al, JACC-HF 1:338-344, 2013. 2- Abi Nasr I et al, EHJ 28: 457–462, 2007. 3- Sehnert AJ, et al. JACC 52:644-651, 2008. Gencaro Gencaro Placebo Placebo Data from the BEST DNA pharmacogenetic substudy for patients with NYHA Class III/IV, LVEF ≤ 35% who were not in AF at randomization.

SLIDE 14

Increases in Hospitalization and Mortality Observed with New AF Onset in Prior HF Study Group ACM Rate (%) CVM Rate (%) CVH Days/Pt HFH Days/Pt New onset AF - No (n = 2202) 15.1 12.8 6.9 6.2 New onset AF - Yes (n = 190) 32.1 28.4 13.3 11.4 Fold increase 2.13 p < 0.0001 2.22 p < 0.0001 1.93 p < 0.0001 1.84 p < 0.0001 Group (N=190) CVH Days/Pt HFH Days/Pt Hospitalized Pre AF event 4.4 3.5 Hospitalized Post AF event 13.8 11.9 Fold increase 3.14 p < 0.0001 3.40 p < 0.0001 HF patients with new onset AF had increased hospitalization and mortality Hospitalization burden increased after experiencing AF event Mortality data are presented as annualized event rates. CVH is adjudicated by committee and HFH is Investigator/CRF determined. p-values are log rank statistic for ACM and CVM and Wilcoxon Rank sum Test for CVH and HFH. Aleong et al. Am J Med. 2014.

SLIDE 15

Phase 2B Genetically-Targeted Trial of gencaro for the Prevention of AF in Patients with HF GENETIC-AF

SLIDE 16

GENETIC-AF: Phase 2B Genetically-Targeted Trial Primary Endpoint: Time to AF/AFL/ACM BUC MET Gencaro: 73/134 (54%) Toprol-XL: 70/133 (53%) Cox proportional hazards model adjusted for the 4 randomization strata: 1) HF etiology, 2) LVEF, 3) rhythm at randomization 4) device type. HR = 1.01 (0.71, 1.42) HR = 0.70 (0.41, 1.19) U.S. Cohort Entire Cohort 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 0 2 4 6 8 10 12 14 16 18 20 22 24 26 Weeks of Efficacy FU Probability of No AF/AFL/ACM Gencaro: 33/60 (55%) Toprol-XL: 40/67 (60%) BUC MET 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 0 2 4 6 8 10 12 14 16 18 20 22 24 26 Weeks of Efficacy FU Probability of No AF/AFL/ACM Piccini et al. JACC-HF 2019. Online ahead of publication: http://heartfailure.onlinejacc.org/content/early/2019/04/25/j.jchf.2019.04.004

SLIDE 17

GENETIC-AF: Time to AF/AFL/ACM Excluding Patients with Long-standing (12+yrs) AF/HF Dx and AF Dx >2 years prior to HF Diagnosis BUC MET Cox proportional hazards model adjusted for: 1) HF etiology, 2) LVEF, 3) rhythm at randomization 4) device type, 5) Previous Class 3 AA use. Gencaro: 46/98 (47%) Toprol-XL: 50/98 (51%) Gencaro: 25/51 (49%) Toprol-XL: 22/40 (55%) 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 0 2 4 6 8 10 12 14 16 18 20 22 24 26 Weeks of Efficacy FU Probability of No AF/AFL/ACM 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 0 2 4 6 8 10 12 14 16 18 20 22 24 26 Weeks of Efficacy FU Probability of No AF/AFL/ACM BUC MET HR = 0.54 (0.33, 0.87) p = 0.011 HR = 0.42 (0.21, 0.86) p = 0.017 0.40 ≤ LVEF ≤ 0.55 LVEF ≤ 0.55 Piccini et al. JACC-HF 2019. Online ahead of publication: http://heartfailure.onlinejacc.org/content/early/2019/04/25/j.jchf.2019.04.004

SLIDE 18

A Phase 3 Trial of gencaro for the Prevention of af in hf Patients with MILD-moderate Left ventricular systolic dysfunction PRECISION-AF

SLIDE 19

GENCARO Development Strategy 1 st Indication for AF in HF with mild-moderate LV dysfunction Clear medical need – no drug therapies shown effective in HFmrEF/HFpEF Label to include BEST heart failure endpoint data in optimal genotype Pivotal Study: PRECISION-AF with FDA SPA Agreement Similar primary endpoint as Phase 2 GENETIC-AF trial 58% treatment effect in GENETIC-AF – allows for 400 patient trial Optimal patient eligibility criteria identified in GENETIC-AF trial Label Expansion for AF into a broader HFpEF population Major unmet medical need in largest HF population Substantial commercial opportunity in USA and/or worldwide Optimized regulatory path – single Phase 3 trial for potential approval

SLIDE 20

FDA agreement that a Phase 3 protocol design, clinical endpoints, trial population and statistical analyses adequately address objectives that, if met, would support an NDA submission Key elements of current agreement Comparative efficacy against TOPROL-XL for prevention of AF recurrence 400 patient sample size, interim review at 200 patients with potential to expand to 550 patients One successful trial to support an NDA with regulatory threshold of p < 0.01 Entry criteria based on precision therapeutic phenotype identified in GENETIC-AF (i.e., AF & HF < 12 years and AF not diagnosed more than 2 years before HF) HF population with LVEF ≥ 40% and < 50% PRECISION-AF FDA Special Protocol Assessment - February 2019

SLIDE 21

LVEF Boundary (Decreasing Ceiling, LVEF ≤ X) Treatment Effect (1-HR) 55 50 45 40 35 30 25 20 10 15 20 25 30 35 40 45 LVEF Boundary (Increasing Floor, LVEF ≥ X) 19% 31% 46% 62% 81% 99% 100% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% 100% 99% 99% 85% 75% 61% 46% 29% 40% 45% 50% 55% 60% 65% X-axis displays DxT12/DTRI-2 population with restrictions on LVEF upper and lower boundary. For example, a LVEF upper boundary of 35% includes all patients with LVEF between the minimum value (12%) and 35%; a LVEF lower boundary of 35% includes all patients with LVEF between the maximum value (53%) and 35%. Entire Cohort Rx Effect Restriction of the population to higher LVEFs leads to greater response Restriction of the population to lower LVEFs leads to loss of response GENETIC-AF: Time to AF/AFL/ACM Improvement in Treatment Effect in Patients with Higher LVEF LVEF ≥ 45% and ≤ 55% HR = 0.39, p = 0.049 50 55 15 10

SLIDE 22

PRECISION-AF Phase 3 Genetically-Targeted Trial Design 125 sites in USA, Canada, Europe and Australia 400 HF patients with ADRB1 Arg/Arg genotype AF in past 120 days, AF/HF DxT < 12 years, AF not >2 years prior to HF LVEF ≥ 40% and < 50% Process underway to expand to LVEF ≥ 40% and ≤ 55% based on GENETIC-AF data and prior FDA guidance Randomization 1:1 to Gencaro or Toprol-XL Primary Endpoint: Time to First Symptomatic AF Event or ACM during 26-week Period 90% power at a = 0.01 to detect a 45% treatment benefit (Phase 2: 58% treatment benefit) Interim analysis at 200 pts with evaluable data Estimated Timeline Enroll 200 pts: 12 monthsInterim data: 18 months Enroll 400 pts: 19 monthsFinal data: 27 months

SLIDE 23

Completed and Anticipated Milestones1 GENETIC-AF Phase 2B top line data reportedFeb 2018 GENETIC-AF data oral presentation at ESC-HF 2018May 2018 GENETIC-AF data at AHA 2018 Nov 2018 FDA SPA Agreement – Gencaro Phase 3 protocolFeb 2019 GENETIC-AF data published in JACC-HFApril 2019 PRECISION-AF Phase 3 clinical trial initiationYE2019 PRECISION-AF interim analysis3Q2021 PRECISION-AF Phase 3 data2Q2022 1- The achievement of all anticipated milestones is subject to the company securing additional financing

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Commercial Opportunity for AF prevention in heart failure Gencaro

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AF Label Expansion Options Prevention of AF in genotype-defined HF population with preserved LV systolic function Commercial opportunity for AF in HF with LVEF >55% HFpEF: “The single largest unmet need in cardiovascular medicine.”1 >2-fold increase in market size compared to HF with LVEF ≥ 40% and ≤ 55% General trial design concept 75-100 HF pts with LVEF > 55%, ADRB1 Arg/Arg genotype, and AF in past 120 days All patients receive LINQ implanted cardiac monitor to assess AF burden Primary Endpoint: Time to First Device-Detected AF Event or ACM Development options for potential label expansion Early read: Expand LVEF criteria in PRECISION-AF based on favorable results Adaptive design: interim analysis to increase sample size for p < 0.05 Stand-alone: Provide preliminary data for future Phase 3 trial 1- Developing Therapies for HFpEF, JACC Heart Fail. 2014

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Gencaro Intellectual Property – Potential Commercial Exclusivity U.S. patents provide longest exclusivity Main patent to mid-2031 Can take to 2034 with S-isomer development; new IP to 2039 NCE exclusivity overlaps: 5+ to 7.5 years from approval United States EMA NCE data exclusivity: 10-11 years post-approval EU Patents extend into 2030, secondary to data exclusivity Japan: patent into 2030 Japan NCE PMS period: 8 years post approval EU & Japan Issued Patents + New Chemical Entity provide ~10 years commercial exclusivity Newly-filed IP based on Phase 2 discoveries would go through 2039 in US and EU

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Additional assets and company structure ARCA biopharma

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ARCA Pipeline – AB171 Thiol-group containing derivative of isosorbide mononitrate Thiol moiety confers antioxidant activity compared to standard nitrates Potentially greater anti-atherosclerosis, prevention of myocardial remodeling, and other favorable biologic effects Dual MOA ® direct NO donor and generates endogenous NO from NOS3 Much greater NO and less peroxynitrite (harmful by-product of NO donation) Markedly pharmacogenetic compared to ISDN or BiDil Enhanced NO generation in a NOS3 major allele homozygote in preclinical studies Pharmacogenetic use patents issued to ARCA in Europe, pending in U.S. Goal is to conduct a Phase 1B POC study in HF, then peripheral artery disease (PAD)

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Oral PDE3A inhibitor with substantial safety dataset Enhanced activity/less tolerance in a PDE3A genetic variant (IP issued in U.S.)1 Orphan indication in pediatric advanced HF i.v. milrinone via indwelling central line widely used and safe/effective in pediatric pre-transplant patients Pediatric cardiologists want/need an oral PDE3A inhibitor to replace i.v. therapy Licensing discussions in progress 1- Sucharov CC et al, J Am Coll Cardiol 73:1173-1184, 2019 ARCA Pipeline – Potential Third Asset

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Capital Structure Shares outstanding (05/08/19)1.1 million Potentially dilutive securities 0.17 million Fully diluted1.27 million Net cash1 (as of 3/31/19)$8.0 million No debt Estimated cash runway to end of 3Q2019 1- Cash and cash equivalents

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Investment Highlights Late stage, genetically-targeted cardiovascular company PRECISION-AF: single pivotal Phase 3 trial for AF in HF│FDA SPA agreement February 2019 Anticipated trial initiation: YE2019│interim data: 3Q2021│topline data: 2Q2022 GencaroTM FDA Fast Track Designation for AF in Genotype-Defined HF Population Large and growing market opportunity for Gencaro Potentially first genetically-targeted cardiovascular therapeutic Significant unmet medical need for AF in HF with no FDA approved treatments Estimated $12.5 billion global atrial fibrillation market by 2020 Gencaro in AF/HF potential annual sales - $500M-$800M in US; similar in EU5 Pharmacogenetic platform with additional cardiovascular programs AB171 – Development for HF, PAD │ IND anticipated mid-2020 Potential third asset – Development for pediatric HF (Orphan Indication) │ In-licensing in progress

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ARCA biopharma Pharmacogenetic Precision Medicine for Cardiovascular Diseases Nasdaq: ABIO