8-K

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):February 26, 2018

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. ☐

Section 2 — Financial Information

Item 2.02. Results of Operations and Financial Condition

On February 26, 2018, ARCA biopharma, Inc. (“ARCA”) issued a press release which included updated cash, cash equivalents and marketable securities balance information.

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, as amended (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, as amended (the “Securities Act”), or the Exchange Act, regardless of any general incorporation language in such filing.

Section 8 — Other Events

Item 8.01. Other Events.

On February 26, 2018, ARCA made the following announcements regarding clinical results from GENETIC-AF, ARCA’s Phase 2B, double-blind, superiority clinical trial evaluating Gencaro^TM (bucindolol hydrochloride) as a genetically-targeted treatment for atrial fibrillation (“AF”) in patients with heart failure and reduced left ventricular ejection fraction (“HFrEF”). In all patients, Gencaro demonstrated a similar treatment benefit compared to the active control, metoprolol succinate (TOPROL-XL). In U.S. patients (127 of 267 total patients), a trend for potential superior benefit in favor of Gencaro (approximately 30% risk reduction over TOPROL-XL), was observed for the primary endpoint of time to recurrence of AF. Additionally, in U.S. patients, Gencaro demonstrated a trend for potential superior benefit in favor of Gencaro (approximately 51% risk reduction over TOPROL-XL) in a subset of patients who underwent continuous heart rhythm monitoring with Medtronic implanted devices. Safety data indicated that Gencaro was generally safe and well-tolerated in the AF/heart failure (“HF”) population investigated with a safety profile similar to TOPROL-XL.

GENETIC-AF enrolled 267 patients from the United States, Canada and Europe. The primary analysis was conducted to evaluate the evidence of safety and superior efficacy of Gencaro versus an active control with demonstrated effectiveness and safety in this patient population TOPROL-XL. The primary endpoint of the trial was time to recurrent AF, atrial flutter (“AFL”) or all-cause mortality (“ACM”). The trial was not powered to conventional significance for this endpoint and utilized Bayesian statistical modeling of predictive probability of success (“PPoS”) of the primary endpoint to estimate outcome if the trial had enrolled 620 patients with 330 primary events.

In all patients, Gencaro demonstrated a similar treatment benefit compared to the active control, TOPROL-XL (143 total events, hazard ratio of 1.01 (95% confidence interval: 0.71, 1.42), which was associated with a PPoS of 14%. In the U.S. patient cohort of 127 patients (approximately 50% of all patients and events), a trend for potential superior benefit in favor of Gencaro over TOPROL-XL was observed (73 events, hazard ratio 0.70, [95% confidence interval: 0.41, 1.19]), with a PPoS of 61%, which was greater than the prespecified criteria set by the company to proceed to Phase 3 development. ARCA believes the difference in treatment effects between the overall and U.S. patient cohorts was primarily due to results in two non-U.S. countries exhibiting hazard ratios >1.0. The differences between patients enrolled at these sites versus the U.S. and other country cohorts are being investigated.

A subgroup of patients underwent continuous (24/7) heart rhythm monitoring via Medtronic implanted loop recorders or other Medtronic implanted therapeutic devices (e.g., ICDs, CRTs) to evaluate daily AF burden. AF burden is defined as the amount of time per day a patient experiences AF. A prespecified time-to-first event analysis was conducted using a total AF burden of at least 6 hours per day to define an event of AF recurrence. In this analysis, hazard ratios of 0.75 (0.43, 1.32) and 0.49 (0.24, 1.04) were observed in the overall (n=69) and U.S. patient (n=42) cohorts, respectively.

Gencaro was generally safe and well-tolerated, with 84% of patients attaining their target dose compared to 72% of patients receiving TOPROL-XL. The most frequently reported adverse events were similar in both groups and consistent with the known safety profile of the beta-blocker class of drugs. Adverse events assessed as related to study drug by the investigator occurred in 23.8% of patients in the Gencaro group and in 30.1% of patients in the TOPROL-XL group. Of note, adverse events of bradycardia were less frequently reported in the Gencaro group (3.7%) compared to patients receiving TOPROL-XL (12.0%). During the 24-week efficacy follow-up period there were three deaths (ACM) in the TOPROL-XL group and none in the Gencaro group. Three patients died in the long-term treatment extension period after receiving Gencaro for more than a year.

ARCA anticipates meeting with the U.S. Food and Drug Administration in the second quarter of 2018 to review Gencaro Phase2 data and potential Phase 3 development plan.

On February 26, 2018, ARCA made a presentation regarding the results described above, 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 may contain forward-looking statements made in reliance upon the safe harbor provisions of Section 27A of the Securities Act and Section 21 E of the Exchange Act.  These statements include, but are not limited to, statements regarding potential Phase 3 development plans for Gencaro, 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, future treatment options for patients with AF, the potential for Gencaro to be the first genetically-targeted AF prevention treatment and the ability of ARCA’s financial resources to support its operations through the end of 2018.  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, 2016, 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 Reports Topline Phase 2B Results for GENETIC-AF Clinical Trial” dated February 26, 2018.
99.2	Investor Presentation titled “ARCA biopharma Investment Community Webcast: Top-line Data from GENETIC-AF Phase 2B Clinical Trial” dated February 26, 2018.

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: February 26, 2018
	ARCA biopharma, Inc.
	(Registrant)
	By:	/s/ Brian L. Selby
		Name:	Brian L. Selby
		Title:	Vice President, Finance and Chief Accounting Officer

EX-99.1

Exhibit 99.1

ARCA Biopharma reports topline Phase 2b results
for genetic-af clinical trial

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Gencaro Demonstrates Comparable Efficacy to Active Control and
Trend for Potential Gencaro Superiority in US Patient Cohort

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ARCA Anticipates Meeting with the U.S. FDA in the Second Quarter of 2018
to Review Phase 2 Data and Phase 3 Development Plan

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Management to Host Conference Call & Webcast Today at 9:00 am ET

Westminster, CO, February 26, 2018 – ARCA biopharma, Inc. (Nasdaq: ABIO), a clinical-stage biopharmaceutical company applying a precision medicine approach to developing genetically-targeted therapies for cardiovascular diseases, today announced clinical results from GENETIC-AF, a Phase 2B, double-blind, superiority clinical trial evaluating Gencaro^TM (bucindolol hydrochloride) as a genetically-targeted treatment for atrial fibrillation (AF) in patients with heart failure and reduced left ventricular ejection fraction (HFrEF). In all patients, Gencaro demonstrated a similar treatment benefit compared to the active control, metoprolol succinate (TOPROL-XL). In U.S. patients (127 of 267 total patients), a trend for potential superior benefit in favor of Gencaro (approximately 30% risk reduction over TOPROL-XL), was observed for the primary endpoint of time to recurrence of AF. Additionally, in U.S. patients, Gencaro demonstrated a trend for potential superior benefit in favor of Gencaro (approximately 51% risk reduction over TOPROL-XL) in a subset of patients who underwent continuous heart rhythm monitoring with Medtronic implanted devices. Safety data indicated that Gencaro was generally safe and well-tolerated in the AF/heart failure (HF) population investigated with a safety profile similar to TOPROL-XL.

GENETIC-AF enrolled 267 patients from the United States, Canada and Europe. The primary analysis was conducted to evaluate the evidence of safety and superior efficacy of Gencaro versus an active control with demonstrated effectiveness and safety in this patient population TOPROL-XL. The primary endpoint of the trial was time to recurrent AF, atrial flutter (AFL) or all-cause mortality (ACM). The trial was not powered to conventional significance for this endpoint and utilized Bayesian statistical modeling of predictive probability of success (PPoS) of the primary endpoint to estimate outcome if the trial had enrolled 620 patients with 330 primary events.

In all patients, Gencaro demonstrated a similar treatment benefit compared to the active control, TOPROL-XL (143 total events, hazard ratio of 1.01 (95% confidence interval: 0.71, 1.42), which was associated with a PPoS of 14%. In the U.S. patient cohort of 127 patients (approximately 50% of all patients and events), a trend for potential superior benefit in favor of Gencaro over TOPROL-XL was observed (73 events, hazard ratio 0.70, [95% confidence interval: 0.41, 1.19]), with a PPoS of 61%, which was greater than the prespecified criteria set by the company to proceed to Phase 3 development. The Company believes the difference in treatment effects between the overall and U.S. patient cohorts was primarily due to results in two non-U.S. countries exhibiting hazard ratios >1.0. The differences between patients enrolled at these sites versus the U.S. and other country cohorts are being investigated.

“The U.S. data support our pre-trial assumptions and provide contemporary information to potentially design Phase 3 development of Gencaro,” commented Dr. Debra Marshall, Senior Vice-President of Medical Affairs. “I would like to thank our clinical investigators, as well as the patients and their families, for their participation in this study.”

A subgroup of patients underwent continuous (24/7) heart rhythm monitoring via Medtronic implanted loop recorders or other Medtronic implanted therapeutic devices (e.g., ICDs, CRTs) to evaluate daily AF burden. AF burden is defined as the amount of time per day a patient experiences AF. A prespecified time-to-first event analysis was conducted using a total AF burden of at least 6 hours per day to define an event of AF recurrence. In this analysis, hazard ratios of 0.75 (0.43, 1.32) and 0.49 (0.24, 1.04) were observed in the overall (n=69) and U.S. patient (n=42) cohorts, respectively.

Gencaro was generally safe and well-tolerated, with 84% of patients attaining their target dose compared to 72% of patients receiving TOPROL-XL. The most frequently reported adverse events were similar in both groups and consistent with the known safety profile of the beta-blocker class of drugs. Adverse events assessed as related to study drug by the investigator occurred in 23.8% of patients in the Gencaro group and in 30.1% of patients in the TOPROL-XL group. Of note, adverse events of bradycardia were less frequently reported in the Gencaro group (3.7%) compared to patients receiving TOPROL-XL (12.0%). During the 24-week efficacy follow-up period there were three deaths (ACM) in the TOPROL-XL group and none in the Gencaro group. Three patients died in the long-term treatment extension period after receiving Gencaro for more than a year.

“We are pleased to share these results from our GENETIC-AF clinical trial. It should be emphasized that the control drug in the study, TOPROL-XL, although not FDA approved for this indication, has demonstrated efficacy in preventing AF in HFrEF. While we did observe some regional heterogeneity in effectiveness of Gencaro, we believe the treatment response observed in the U.S. population, which represents approximately half of the overall study population, support continued development of Gencaro as a genetically-targeted treatment for atrial fibrillation,” commented Dr. Michael Bristow, ARCA’s President and CEO. “As in all Phase 2 trials, which in part are conducted to elicit information relevant to the design for Phase 3, elucidation of the reason(s) for regional heterogeneity could prove valuable for Phase 3 trial design.”

ARCA anticipates meeting with the U.S. Food and Drug Administration (FDA) in the second quarter of 2018 to review Gencaro Phase 2 data and potential Phase 3 development plan.

ARCA ended 2017 with cash, cash equivalents and marketable securities totaling $11.8 million (unaudited) and believes that these funds, with additional net proceeds of approximately $3.4 million (unaudited) raised in January 2018 through its existing “At-the-Market” offering facility, will be sufficient to fund its operations, at its projected cost structure, through the end of 2018.

GENETIC-AF Clinical Trial

GENETIC-AF is a Phase 2B, multi-center, randomized, double-blind, superiority clinical trial comparing the safety and efficacy of Gencaro to Toprol-XL (metoprolol succinate) for the treatment and prevention of recurrent atrial fibrillation or atrial flutter (AF/AFL) in heart failure patients with reduced left ventricular ejection fraction (HFrEF). Eligible patients had HFrEF, a history of paroxysmal AF (episodes lasting 7 days or less) or persistent AF (episodes lasting more than 7 days and less than 1 year) in the past 6 months, and the beta-1 389 arginine homozygous genotype that ARCA believes responds most favorably to Gencaro.

Conference Call and Webcast

ARCA will hold a conference call and live audio webcast today, Monday, February 26, 2018 at 9:00 am Eastern (7:00am Mountain) to discuss results from the GENETIC-AF clinical trial.

Participant Toll-Free Dial-In Number: 1-877-270-2148

Participant International Dial-In Number: 1-412-902-6510

Ask to be joined into the ARCA biopharma call.

Presentation slides to accompany the conference call have been posted to the Presentations page in the investor section of the ARCA website, www.arcabio.com.

Interested parties may access a live audio webcast of the conference call at: https://services.choruscall.com/links/abio180226.html. Please connect to the ARCA website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary. The webcast will be archived for 90 days.

About Gencaro^TM (bucindolol hydrochloride)

Gencaro (bucindolol hydrochloride) is an investigational, pharmacologically unique beta-blocker and mild vasodilator being developed for the treatment of AF. Gencaro is considered part of the beta-blocker class of compounds because of its property of blocking both beta-1 and beta-2 receptors in the heart. The blocking of these receptors prevents them from binding with other molecules, primarily the neurotransmitter norepinephrine, which activate these receptors. ARCA believes that Gencaro is well-tolerated in cardiovascular patients because of its mild vasodilator effects. Originally developed by Bristol-Myers Squibb, the active pharmaceutical ingredient in Gencaro, bucindolol hydrochloride, has been tested clinically in approximately 4,500 patients, including over 3,250 patients in eight clinical trials in HFrEF patients. Gencaro was the subject of a Phase 3 HF mortality trial in 2,708 patients, mostly in the United States (the “BEST trial”). The BEST trial included a DNA bank of over 1,000 patients, which was used to evaluate the effect of genetic variation on patients’ response to Gencaro.

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 patients with AF and HFrEF which recently completed a Phase 2B clinical trial. 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. ARCA has a collaboration with Medtronic, Inc. for support of the GENETIC-AF trial. The Gencaro development program has been granted Fast Track designation by FDA. ARCA also plans to develop AB171, a thiol-substituted isosorbide mononitrate, as a potential genetically-targeted treatment for peripheral arterial disease (PAD) and for HF. For more information, please visit www.arcabio.com.

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 potential Phase 3 development plans for Gencaro, 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, future treatment options for patients with AF, the potential for Gencaro to be the first genetically-targeted AF prevention treatment and the ability of ARCA’s financial resources to support its operations through the end of 2018.  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, 2016, 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

###

EX-99.2

ARCA biopharma Investment Community Webcast: Top-line Data from GENETIC-AF Phase 2B Clinical Trial Nasdaq: ABIO February 26, 2018 Exhibit 99.2

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, statements regarding potential Phase 3 development plans and timing for potential future Gencaro development, 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, future treatment options for patients with AF, the potential for Gencaro to be the first genetically-targeted AF prevention treatment, the potential for future development of AB171 and associated potential timing, and the ability of ARCA’s financial resources to support its operations through the end of 2018. 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, 2016, and subsequent filings. ARCA disclaims any intent or obligation to update these forward-looking statements.

United Kingdom National Health Service, Atlas of Risk, 2017 Cardiovascular Disease By 2030, 43.9% of the US population is projected to have some form of cardiovascular disease1 1 - AHA Statistical Update – Heart and Stroke Stats 2017, p204

The Problem: Inconsistent Therapeutic Response Across Patients Modified from Spear et al., Trends Mol Med, 2001; 2 Lazarou et al., JAMA, 1998 Individual variations in response to drugs and drug toxicity is common in clinical and marketed drug settings. ~10% of drugs are withdrawn from market post-launch due to adverse drug reactions. Genetic targeting: Intends to enable patient selection for higher response rates with lower side effects b-blockers in HF b-blockers in AF

AF in HFrEF – An Unmet Medical Need A top unmet need for AF treatment are pharmacotherapies for patients with comorbid chronic heart failure1 No FDA approved drugs for this indication Currently approved antiarrhythmic agents for non-HFrEF patients are associated with significant side effects: Most are contraindicated or have warnings for HFrEF New onset AF markedly worsens HF morbidity & mildly increases mortality β-blockers approved for HFrEF but used off-label for AF have demonstrated only limited efficacy No agents approved for AF or HFrEF have genetically influenced clinical response for arrhythmia events Source(s)/Note(s): 1 – Decision Resources Group, “Atrial Fibrillation, December 2014”, p1 AHA; Atrial Fibrillation, 5/3/07: www.americanheart.org, eMedicine, Atrial Fibrillation, Jan. 2007: http://www.emedicine.com/med/topic184.htm ; Decision Resources, Cardium: Atrial Fibrillation, 2003.

Gencaro for Atrial Fibrillation in Genotype-Defined Heart Failure Population AF in HFREF No FDA approved drugs for this indication U.S. FDA Fast Track Designation (April 2015) AF HF

Gencaro (bucindolol hydrochloride) Compound β-blocker/vasodilator – well characterized drug class β-blockers target cardiac myocytes to reduce adverse β1- adrenergic signaling that causes cardiac chamber remodeling Well characterized safety profile IP protection through 2030 Unique MOA Competitive antagonism Sympatholysis – norepinephrine (NE) lowering Inverse agonism – inactivation of constitutively active receptors Other β-blockers lack these last 2 properties Genotype Specific Response Clinical response differentiated by patient genetic profile Via 2 specific adrenergic receptor (AR) polymorphisms – β1- and α2c Optimal genotype is ADRB1 Arg389Arg – present in 50% of U.S. population ARCA & LabCorp jointly developed companion diagnostic test

MERIT-HF (AF as AE + ECG) van Veldhuisen D J et al. Eur J Heart Fail; 8:539-546 2006 HR = 0.59 (0.44 – 0.79) P-value = 0.0004 Bucindolol = 75/1202 (6.2%) Placebo = 115/1190 (9.7%) Risk reduction 41% BEST (AF as AE + ECG) HR = 0.52 (0.37 – 0.75) P-value = 0.0004 Metoprolol = 47/1569 (3.0%) Placebo = 85/1563 (5.4%) Risk reduction 48% Effect of b-blockers on prevention of new onset AF in heart failure mortality trials Aleong RG et al, JACC-HF 1:338-344, 2013

b1389 Arg/Arg , DNA substudy (n = 441; 36 events ) Hazard Ratio = 0.26 (0.12 – 0.57) P-value = 0.0003 Hazard Ratio = 1.01 (0.56 – 1.84) P-value = 0.97 b1389 Gly carriers, DNA substudy (n = 484; 44 events) RES = (Ln 0.26/Ln 0.57 ) = 2.40 Interaction p = 0.008 Kaplan-Meier curves for prevention of atrial fibrillation in BEST: DNA substudy (Aleong et al, JACC Heart Fail; 1:338-44, 2013) BEST DNA substudy (Pts in SR @ Bsl) (n = 925; 80 events ) Hazard Ratio = 0.57 (0.36 – 0.90) P-value = 0.014

LVEF <0.50, HFrEF (not Class IV); current/recent Hx of persistent or paroxysmal Sx AF (<180 days) Bucindolol Toprol XL ECV @ 3 wks if AF present Randomization: ADRB1 Arg389Arg genotype Trial sites: U.S, Canada & Europe 1:1 Phase 2B Enrollment N = 267 24-week Follow-up for 1EP + Blinded Treatment Extension Period GENETIC-AF: Phase 2B Superiority Trial Bucindolol vs. Toprol XL, Prevention of Recurrent AF in HFrEF Patients with the b1389 Arg/Arg Genotype

Randomized subjects N or Other Participating countries U.S., Canada, Hungary, Serbia, Poland, Netherlands Randomized N: Total/U.S./ROW 267 / 127 / 140 Primary endpoint Time to AF/AFL/ACM (symptomatic or asymptomatic AF/AFL), 24 weeks Sample size based on Ph2B/3 seamless design Sample size to detect a Bayesian modeled Predictive Probability of Success (PPoS) of ≥40%, with an effect size of 25% Events N: Total/U.S./ROW 143 / 73 / 70 Event rates: Total/U.S./ROW 54% / 57% / 50% Length of Follow-up 24 weeks efficacy, then long term (mean 11.3 months) Age 60s NYHA Class I/II/III per protocol LVEF <0.50 per protocol; mean mid 0.30s Type of AF at randomization ~50% in AF, 50% sinus rhythm w/history of AF w/in 6mos. Background therapy ≥90% on beta-blockers, switched to study medication at randomization. No background anti-arrhythmic drugs. General protocol adherence Excellent (e.g. high % study drug target, 93% on OACs) GENETIC-AF: Baseline Characteristics and General Outcomes

Parameter Result Target drug doses achieved Gencaro 84%; Toprol-XL 72% Hazard ratio (HR), All Subjects 1.01 (0.71,1.42) Predictive probability (PPoS), All* 14.4% AF Burden sub-study HR, All (N = 69) 0.75 (0.43,1.32) HR, U.S. 0.70 (0.41,1.19) PPoS, U.S. 60.6% HR, ROW 1.34 (0.79,2.28) All-cause mortality (safety endpoint) 3 Toprol-XL arm, 0 Gencaro during 24 weeks; full follow-up annualized mortality rate 2.4% Toprol-XL, 2.4% Gencaro Number of Strokes (93% on OACs) 0 Toprol-XL (1 TIA); 0 Gencaro General safety SAEs 7.5% Toprol-XL, 6.0% Gencaro AEs 71.4% Toprol-XL, 74.6% Gencaro Less bradycardia AEs with Gencaro *Based on an N of 620 subjects, 330 events for a Ph 3 trial GENETIC-AF Top-line Results

Regional Heterogeneity in Treatment Effect In two of six ex-U.S. countries, patient selection differences led to differences in key baseline characteristics that could be expected to differentially affect outcomes. This and other hypotheses for regional heterogeneity are being further explored.

GENETIC-AF Clinical Trial Firsts 1st prospectively designed and conducted randomized, controlled trial (RCT) for prevention of atrial fibrillation (AF) in heart failure (HFrEF) 1st RCT in an AF-risk study population to compare atrial fibrillation burden (AFB) to clinical/ECG determined primary endpoints 1st cardiovascular, pharmacogenetically-targeted RCT to report data 1st beta-blocker RCT to measure CYP2D6 genetic variants and relate these to effectiveness and safety 1st beta-blocker RCT to include heart failure with moderately reduced ejection fraction (HFmREF) in the inclusion criteria (LVEF 0.40-0.49)

GENETIC-AF Conclusions Overall trial quality excellent Safety profile comparable or better (fewer bradycardia AEs) to metoprolol succinate (TOPROL-XL) Comparable efficacy to active control in overall population (hazard ratio (HR) 1.01) Trend for potential Gencaro superiority in U.S. patients observed Clinical/ECG determined primary endpoint (HR 0.70 [0.41,1.19]) AF Burden (HR 0.49 [0.24, 1.04]) Clear evidence of regional heterogeneity Likely due to country-specific differences in AF/HF referral patterns Will require further study for confirmation

Next Steps Continue pharmacogenetic drug development of two assets Gencaro AB171 Complete full analysis of GENETIC-AF trial data including explanation of regional heterogeneity Meet with FDA to review in 2Q2018 Gencaro Phase 2 data Potential Phase 3 development plan Present GENETIC-AF results at major CV scientific conference in 2018 Initiate clinical development of AB-171 Pharmacogenetic targeting in Peripheral Arterial Disease (PAD) & HFrEF

ARCA biopharma Nasdaq: ABIO February 26, 2018 Pharmacogenetic Precision Medicine for Cardiovascular Diseases