GENETIC-AF - A Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients With Heart Failure

This study is being done to compare the effects of bucindolol hydrochloride (bucindolol) to metoprolol succinate (Toprol-XL) on the recurrence of symptomatic atrial fibrillation/atrial flutter in patients with heart failure who have a specific genotype for the beta-1 adrenergic receptor.

Start Date01 Apr 2014

Sponsor / Collaborator

ARCA biopharma, Inc.

[+1]

100 Clinical Results associated with Bucindolol hydrochloride

100 Translational Medicine associated with Bucindolol hydrochloride

100 Patents (Medical) associated with Bucindolol hydrochloride

253

Literatures (Medical) associated with Bucindolol hydrochloride

01 Sep 2023·Drugs in R&D

Comparative Efficacy of Different Drugs for the Treatment of Dilated Cardiomyopathy: A Systematic Review and Network Meta-analysis.

Review

Author: Zhou, Xiaomin ; Shen, Lijuan ; Lu, Shu ; Tong, Xinyu ; Chang, Sheng ; Wang, Yudan

BACKGROUND AND OBJECTIVE:

At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis.

METHODS:

The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis.

RESULTS:

There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR).

CONCLUSION:

A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.

01 Aug 2022·Journal of internal medicineQ1 · MEDICINE

Network meta‐analysis of medical therapy efficacy in more than 90,000 patients with heart failure and reduced ejection fraction

Q1 · MEDICINE

Article

Author: Tricarico, Lucia ; De Marzo, Vincenzo ; Savarese, Gianluigi ; Hassan, Sofia ; Iacoviello, Massimo ; Ameri, Pietro ; Porto, Italo

Abstract:

Background:

Following the availability of new drugs for chronic heart failure (HF) with reduced ejection fraction (HFrEF), we sought to provide an updated and comparative synthesis of the evidence on HFrEF pharmacotherapy efficacy.

Methods:

We performed a Bayesian network meta‐analysis of phase 2 and 3 randomized controlled trials (RCTs) of medical therapy in HFrEF patient cohorts with more than 90% of the participants with left ventricular ejection fraction less than 45% and all‐cause mortality reported.

Results:

Sixty‐nine RCTs, accounting for 91,741 subjects, were evaluated. The step‐wise introduction of new drugs progressively decreased the risk of all‐cause death, up to reaching a random‐effects hazard ratio (HR) of 0.43 (95% credible intervals [CrI] 0.27–0.63) with beta blockers (BB), angiotensin‐converting enzyme inhibitors (ACEi), and mineralocorticoid receptor antagonist (MRA) versus placebo. The risk was further reduced by adding sodium–glucose cotransporter‐2 inhibitors (SGLT2i; HR 0.38, 95% CrI 0.22–0.60), ivabradine (HR 0.39, 95% CrI 0.21–0.64), or vericiguat (HR 0.40, 95% CrI 0.22–0.65) to neurohormonal inhibitors, and by angiotensin receptor–neprilysin inhibitor (ARNI), BB, and MRA (HR 0.36, 95% CrI 0.20–0.60). In a sensitivity analysis considering the ARNI and non‐ARNI subgroups of SGLT2i RCTs, the combination SGLT2i + ARNI + BB + MRA was associated with the lowest HR (0.28, 95% CrI 0.16–0.45 vs. 0.40, 95% CrI 0.24–0.60 for SGLT2i + BB + ACEi + MRA). Consistent results were obtained in sensitivity analyses and by calculating surface under the cumulative ranking area, as well as for cardiovascular mortality (information available for 56 RCTs), HF hospitalization (45 RCTs), and all‐cause hospitalization (26 RCTs).

Conclusions:

Combination medical therapy including neurohormonal inhibitors and newer drugs, especially ARNI and SGLT2i, confers the maximum benefit with regard to HFrEF prognosis.

01 Jul 2022·Biochemistry. Biokhimiia

Agonists in the Extended Conformation Stabilize the Active State of β-Adrenoceptors

Article

Author: Ryazanov, Alexey G ; Meshcheryakova, Olga V ; Efimov, Alexander V

Abstract:

In this study, we conducted a comparative analysis of the structure of agonists and antagonists of transmembrane (TM) β-adrenoceptors (β-ARs) and their interactions with the β-ARs and proposed the mechanism of receptor activation. A characteristic feature of agonist and antagonist molecules is the presence of a hydrophobic head (most often, one or two aromatic rings) and a tail with a positively charged amino group. All β-adrenergic agonists have two carbon atoms between the aromatic ring of the head and the nitrogen atom of the amino group. In antagonist molecules, this fragment can be either reduced or increased to four atoms due to the additional carbon and oxygen atoms. The agonist head, as a rule, has two H-bond donors or acceptors in the para- and meta-positions of the aromatic rings, while in the antagonist heads, these donors/acceptors are absent or located in other positions. Analysis of known three-dimensional structures of β-AR complexes with agonists showed that the agonist head forms two H-bonds with the TM5 helix, and the tail forms an ionic bond with the D3.32 residue of the TM3 helix and one or two H-bonds with the TM7 helix. The tail of the antagonist can form similar bonds, but the interaction between the head and the TM5 helix is much weaker. As a result of these interactions, the agonist molecule acquires an extended “strained string” conformation, in contrast to the antagonist molecule, which has a longer, bended, and flexible tail. The “strained string” of the agonist interacts with the TM6 helix (primarily with the W6.48 residue) and turns it, which leads to the opening of the G protein-binding site on the intracellular side of the receptor, while flexible and larger antagonist molecules do not have the same effect on the receptor.

News (Medical) associated with Bucindolol hydrochloride

01 Aug 2024

·www.globenewswire.com

ARCA biopharma Announces Second Quarter 2024 Financial Results and Provides Corporate Update

WESTMINSTER, Colo., Aug. 01, 2024 (GLOBE NEWSWIRE) -- ARCA biopharma, Inc. (Nasdaq: ABIO), (the “Company”) a biopharmaceutical company applying a precision medicine approach to developing genetically targeted therapies for cardiovascular diseases, today reported second quarter 2024 financial results and provided a corporate update. In April 2022, ARCA established a Special Committee of the board of directors (the “Board”) of ARCA to conduct a comprehensive review of strategic alternatives. As part of the strategic review process, the Company explored potential strategic alternatives that included, without limitation, an acquisition, merger, business combination or other transactions. The Company has and is continuing to explore strategic alternatives related to its product candidates and related assets, including, without limitation, licensing transactions and asset sales. On April 3, 2024, following a comprehensive review of strategic alternatives, the Company, Atlas Merger Sub Corp., a Delaware corporation and a wholly-owned subsidiary of ARCA (“Merger Sub I”), Atlas Merger Sub II LLC, a Delaware limited liability company and a wholly-owned subsidiary of ARCA (“Merger Sub II”) and Oruka Therapeutics, Inc., a Delaware corporation (“Oruka”), entered into an Agreement and Plan of Merger and Reorganization (the “Merger Agreement”), pursuant to which, among other matters, and subject to the satisfaction or waiver of the conditions set forth in the Merger Agreement, Merger Sub I will merge with and into Oruka, with Oruka continuing as a wholly owned subsidiary of ARCA and the surviving corporation of such merger (the “First Merger”) and as part of the same overall transaction, the surviving corporation in the First Merger will merge with and into Merger Sub II with Merger Sub II continuing as a wholly owned subsidiary of ARCA and the surviving entity of such merger (the “Second Merger” and together with the First Merger, the “Merger”). The Merger is intended to qualify for federal income tax purposes as a tax-free reorganization under the provisions of Section 368(a) of the Internal Revenue Code of 1986, as amended. Additional descriptions about the Merger Agreement and related agreements were previously disclosed on a Current Report on Form 8-K filed with the U.S. Securities and Exchange Commission (the “SEC”) on April 3, 2024. In connection with the proposed Merger, the Company has filed relevant materials with the SEC, including a registration statement on Form S-4 that contains a definitive proxy statement and prospectus of the Company. In connection with the Merger, the Company will dispose of (or is in the process of disposing of) its legacy technology and intellectual property, including those related to Gencaro™ (bucindolol hydrochloride) and Recombinant Nematode Anticoagulant Protein c2 (“rNAPc2”). Any such disposal of legacy technology and intellectual property will be contingent upon obtaining stockholder approval for the Merger and is expected to occur immediately prior to or concurrently with the closing of the Merger. In the event that the Company shall enter into an agreement for any such sale or other disposition of its legacy assets at or prior to the closing of the Merger, the net proceeds received at or prior to the closing of the Merger will be included in the calculation of the net cash of the Company as of the closing. The Company’s future operations are highly dependent on the success of the Merger and there can be no assurances that the Merger will be successfully consummated. In the event that the Company does not complete the Merger, the Company may explore strategic alternatives, including, without limitation, another strategic transaction and/or pursue a dissolution and liquidation of the Company. Second Quarter 2024 Summary Financial Results Cash and cash equivalents were $33.3 million as of June 30, 2024, compared to $37.4 million as of December 31, 2023. ARCA believes that its current cash and cash equivalents, consisting primarily of money market funds, will be sufficient to fund its operations through the end of 2025. Our future viability beyond that point is dependent on the results of the strategic review process and our ability to raise additional capital to fund our operations. We expect to continue to incur costs and expenditures in connection with the process of evaluating strategic alternatives. There can be no assurance, however, that we will be able to successfully consummate any particular strategic transaction, including the Merger. The process of continuing to evaluate these strategic options may be very costly, time-consuming and complex and we have incurred, and may in the future incur, significant costs related to this continued evaluation, such as legal, accounting and advisory fees and expenses and other related charges. General and administrative (G&A) expenses were $3.0 million for the quarter ended June 30, 2024, compared to $1.7 million for the corresponding period in 2023, an increase of approximately $1.3 million. During the three months ended June 30, 2024, we recorded $370,000 for one-time termination benefits related to the separation of Dr. Michael Bristow, the former Chief Executive Officer of ARCA, effective April 3, 2024. The increase for the three month period was primarily the result of a $0.9 million increase in professional fees primarily related to the Merger Agreement discussed above and $0.4 million higher one-time termination benefits from the termination discussed above in 2024. G&A expenses in 2024 are expected to be higher than those in 2023 as we incur professional fees related to the Merger Agreement discussed above and maintain administrative activities to support our ongoing operations. We expect to incur significant costs related to our exploration of strategic alternatives and the Merger, including legal, accounting and advisory expenses and other related charges. Research and development (R&D) expenses were $0.1 million for the quarter ended June 30, 2024, compared to $0.3 million for the corresponding period in 2023. Of the $0.2 million decrease in R&D expenses in the second quarter of 2024 as compared to the second quarter of 2023, $0.1 million was primarily related to decreased headcount and $0.1 million was primarily related to the unrestricted research grants with ARCA’s former President and Chief Executive Officer’s academic research laboratory at the University of Colorado. There was no expense under these arrangements for the three months ended June 30, 2024. Total expense under these arrangements for the three months ended June 30, 2023 was $0.1 million. In December 2023, the Company made a payment of $125,000 for the grant period July 2022 through December 2023 under these arrangements. As discussed above, the former President and Chief Executive Officer resigned in April 2024. R&D expense in 2024 is expected to be lower than 2023 while we explore strategic alternatives. Should we resume clinical trials of product candidates, we expect research and development costs to increase significantly for the foreseeable future as our product candidate development programs progress. Total operating expenses for the quarter ended June 30, 2024 were $3.1 million compared to $2.0 million for the second quarter of 2023. Net loss for the quarter ended June 30, 2024 was $2.7 million, or $0.18 per basic and diluted share, compared to $1.5 million, or $0.10 per basic and diluted share in the second quarter of 2023. About ARCA biopharmaARCA biopharma is dedicated to developing genetically and other targeted therapies for cardiovascular diseases through a precision medicine approach to drug development. 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 concerning ARCA, Oruka, the proposed pre-closing financing and the proposed merger between ARCA and Oruka (collectively, the “Proposed Transactions”) and other matters. These statements include, but are not limited to, express or implied statements relating to ARCA’s or Oruka’s management team’s expectations, hopes, beliefs, intentions or strategies regarding the future including, without limitation, statements regarding: the Proposed Transactions and the expected effects, perceived benefits or opportunities, including investment amounts from investors and expected proceeds, and related timing with respect thereto, expectations regarding or plans for discovery, preclinical studies, clinical trials and research and development programs, in particular with respect to ORKA-001 and ORKA-002, and any developments or results in connection therewith, including the target product profile of each of ORKA-001 and ORKA-002; the anticipated timing of the commencement of and results from those studies and trials; expectations regarding the use of proceeds, the sufficiency of post-transaction resources to support the advancement of Oruka’s pipeline through certain milestones and the time period over which Oruka’s post-transaction capital resources will be sufficient to fund its anticipated operations; the cash balance of the combined entity at closing; expectations regarding the treatment of psoriasis and associated diseases; expectations related to ARCA’s contribution and payment of dividends in connection with the Merger, including the timing thereof; the expected trading of the combined company’s stock on Nasdaq under the ticker symbol “ORKA;” potential future development plans for Gencaro, including ARCA’s ability to continue development of Gencaro; ARCA’s ability to secure sufficient financing to support any clinical trials for Gencaro: and the ability of ARCA’s financial resources to support its operations at the current levels through the end of fiscal year 2025, ARCA’s ability to obtain additional funding when needed or enter into a strategic or other transaction, the extent to which ARCA’s issued and pending patents may protect ARCA’s 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, or ARCA’s ability to maintain listing of its common stock on a national exchange. 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, 2023 and the registration statement on Form S-4, as amended, filed with the SEC, and subsequent filings. ARCA disclaims any intent or obligation to update these forward-looking statements. All forward-looking statements in this press release are current only as of the date hereof and, except as required by applicable law, ARCA undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. All forward-looking statements are qualified in their entirety by this cautionary statement. No Offer or Solicitation This press release and the information contained herein is not intended to and does not constitute (i) a solicitation of a proxy, consent or approval with respect to any securities or in respect of the Proposed Transactions or (ii) an offer to sell or the solicitation of an offer to subscribe for or buy or an invitation to purchase or subscribe for any securities pursuant to the Proposed Transactions or otherwise, nor shall there be any sale, issuance or transfer of securities in any jurisdiction in contravention of applicable law. No offer of securities shall be made except by means of a prospectus meeting the requirements of the Securities Act of 1933, as amended, or an exemption therefrom. Subject to certain exceptions to be approved by the relevant regulators or certain facts to be ascertained, the public offer will not be made directly or indirectly, in or into any jurisdiction where to do so would constitute a violation of the laws of such jurisdiction, or by use of the mails or by any means or instrumentality (including without limitation, facsimile transmission, telephone and the internet) of interstate or foreign commerce, or any facility of a national securities exchange, of any such jurisdiction. NEITHER THE SEC NOR ANY STATE SECURITIES COMMISSION HAS APPROVED OR DISAPPROVED OF THE SECURITIES OR DETERMINED IF THIS PRESS RELEASE IS TRUTHFUL OR COMPLETE. Important Additional Information About the Proposed Transactions Will be Filed with the SEC This press release is not a substitute for the registration statement on Form S-4 or any other document that ARCA has filed or may file with the SEC in connection with the Proposed Transactions. In connection with the Proposed Transactions, ARCA has filed with the SEC a registration statement on Form S-4, which contains a proxy statement/prospectus of ARCA. ARCA URGES INVESTORS AND STOCKHOLDERS TO READ THE REGISTRATION STATEMENT ON FORM S-4, PROXY STATEMENT/PROSPECTUS AND ANY OTHER RELEVANT DOCUMENTS THAT ARE OR MAY BE FILED WITH THE SEC, AS WELL AS ANY AMENDMENTS OR SUPPLEMENTS TO THESE DOCUMENTS, CAREFULLY AND IN THEIR ENTIRETY, BECAUSE THEY DO AND WILL CONTAIN IMPORTANT INFORMATION ABOUT ARCA, ORUKA, THE PROPOSED TRANSACTIONS AND RELATED MATTERS. Investors and stockholders can obtain free copies of the proxy statement/prospectus and other documents filed by ARCA with the SEC through the website maintained by the SEC at www.sec.gov. Stockholders are urged to read the proxy statement/prospectus and the other relevant materials filed with the SEC before making any voting or investment decision with respect to the Proposed Transactions. In addition, investors and stockholders should note that ARCA communicates with investors and the public using its website (https://arcabio.com/investors/). Participants in the Solicitation ARCA, Oruka and their respective directors and executive officers may be deemed to be participants in the solicitation of proxies from stockholders in connection with the Proposed Transactions. Information about ARCA’s directors and executive officers including a description of their interests in ARCA is included in ARCA’s most recent Annual Report on Form 10-K, including any information incorporated therein by reference, as filed with the SEC. Information about ARCA’s and Oruka’s respective directors and executive officers and their interests in the Proposed Transactions is included in the proxy statement/prospectus relating to the Proposed Transactions filed with the SEC. Investor & Media Contact:Jeff Dekker720.940.2122ir@arcabio.com ARCA BIOPHARMA, INC.BALANCE SHEET DATA(in thousands)(unaudited) June 30, 2024December 31, 2023Cash and cash equivalents$33,283$37,431Working capital$32,549$36,955Total assets$33,844$37,861Total stockholders’ equity$32,573$37,020 ARCA BIOPHARMA, INC. STATEMENTS OF OPERATIONS(unaudited) Three Months EndedJune 30, Six Months EndedJune 30, 2024 2023 2024 2023 (in thousands, except share and per share amounts) Costs and expenses: General and administrative$2,992 $1,719 $5,309 $3,125 Research and development 130 254 295 644 Total costs and expenses 3,122 1,973 5,604 3,769 Loss from operations (3,122) (1,973) (5,604) (3,769) Interest and other income 444 493 917 943 Net loss$(2,678) $(1,480) $(4,687) $(2,826) Net loss per share: Basic and diluted$(0.18) $(0.10) $(0.32) $(0.20)Weighted average shares outstanding: Basic and diluted 14,506,879 14,410,143 14,504,011 14,410,143

Financial StatementAcquisitionExecutive ChangeIPO

26 Feb 2018

·www.biospace.com

Shares Plunge as ARCA biopharma’s Gencaro Had Mixed Phase II Clinical Trial Results

This is the Average Interview Process Time for a B ARCA biopharma announced positive headline results from its Phase IIb clinical trial of Gencaro, but investors aren’t buying the positive spin. ARCA biopharma , based in Westminster, Colorado, announced positive results from its Phase IIb clinical trial of Gencaro (bucindolol hydrochloride) in patients with atrial fibrillation (AF). However, there appears to be some cherry-picking of the data to give it a positive spin, rather than a more lukewarm, or potentially negative results. And investors have responded with shares down 56 percent in premarket trading. The company’s clinical trial, GENETIC-AF, evaluated 267 patients from the U.S., Canada and Europe. Patients had AF with heart failure and reduced left ventricular ejection fraction (HFrEF). All patients showed a similar benefit compared to the active control, metoprolol succinate (TOPROL-XL). Which is to say, it didn’t show superiority, which was the goal of the trial. However, in population subsets, it did show superiority. In the U.S. patients, 127 of 267 total patients, there was a trend of superior benefit, showing about a 30 percent risk reduction over TOPROL-XL. They also trended in a subset of patients whose heart rhythm was continuously monitored with Medtronic implanted devices, showing about a 51 percent risk reduction over TOPROL-XL. The primary endpoint was time to recurrent AF, atrial flutter (AFL) or all-cause mortality (ACM). The company noted, “The trial was not powered to conventional significance for its 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.” Gencaro is a beta-blocker and mild vasodilator. Originally developed by Bristol-Myers Squibb Company , the active pharmaceutical ingredient, bucindolol hydrochloride, has been clinically tested in about 4,500 patients, including more than 3,250 patients in eight clinical trials in HFrEF patients. “We are pleased to share these results from our GENETIC-AF clinical trial,” said Michael Bristow, ARCA’s president and chief executive officer, in a statement. “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. As in all Phase II trials, which in part are conducted to elicit information relevant to the design for Phase III, elucidation of the reason(s) for regional heterogeneity could prove valuable for Phase III trial design.” The company expects to meet with the U.S. Food and Drug Administration (FDA) in the second quarter of this year to review the Phase II data and develop a Phase III plan and trial structure. Investors appear doubtful, but many clinical trials are being built on subpopulation results, so the company may have a route forward, particularly given that the company’s focus is on genetically-identified treatments. On November 16, 2017, the company announced that the European Patent Office issued a patent (EPO #2515899) for methods of treating cardiovascular disease and conditions with a thiol-substituted isosorbide mononitrate based on genetic targeting. The patent has been validated in 10 countries, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, Sweden, Switzerland and the UK. Related patents are pending in the U.S. and Canada. “ARCA was founded on the belief that a precision medicine approach to drug development, tailoring medical treatment to functionally important genetic variants in drug targets that also serve as biomarkers, can enable more effective therapies, improve patient outcomes and reduce healthcare costs,” said Bristow, in a statement at the time. “The addition of AB171 to our genetically-targeted development pipeline, including the Gencaro atrial fibrillation-heart failure program, is consistent with that mission. We believe our experience with GENETIC-AF has established the feasibility of in-house design and execution of pharmacogenetics clinical trials, and has provided invaluable insights into this type of drug development.”

Clinical ResultPhase 2Phase 3

13 Mar 2006

·www.biospace.com

Aeolus Pharmaceuticals Inc. Receives $350,000 Milestone Payment And Equity Interest From Cardiovascular Company

SAN DIEGO, March 13 /PRNewswire-FirstCall/ -- Aeolus Pharmaceuticals, Inc. , a developer of a new class of disease-modifying compounds with potent activity in pre-clinical models of central nervous system diseases and oncology, announced today that it has received a milestone payment and equity consideration from ARCA Discovery, Inc., a privately held cardiovascular-focused company ("ARCA"). In 2003, CPEC, LLC ("CPEC"), a limited liability company owned by Aeolus (35%) and Indevus Pharmaceuticals, Inc. (65%), out-licensed all rights to a potential therapeutic compound referred to as "bucindolol" to ARCA. Both the cash payment and equity consideration received by Aeolus are based upon Aeolus' ownership interest in CPEC, and a renegotiation of certain terms of the 2003 agreement between CPEC and ARCA. Richard P. Burgoon, Jr., Chief Executive Officer to Aeolus, noted that, "The cash payment from this milestone will be used to further the development of Aeolus' catalytic antioxidant technology." Mr. Burgoon further commented that, "We are pleased to see progress in the development of bucindolol, a compound with potential for the treatment of heart failure." The $350,000 payment received by Aeolus was triggered by ARCA receiving investment funding. The equity consideration to Aeolus was consideration for a modification of the license agreement between CPEC and ARCA. Future milestone payments and royalty payments to Aeolus, if any, while provided for under the agreement between CPEC and ARCA, can not be assured nor guaranteed. Bucindolol was previously evaluated in Phase III clinical studies, and although the drug was found to be safe, these prior Phase III clinical studies were discontinued in 1999 following an interim analysis of the data. The interim data analysis revealed that some subpopulations within the study appeared to benefit from the drug, while other subpopulations did not. In total, bucindolol has been evaluated in Phase III clinical trails involving more than 3,000 patients with advanced heart failure and myocardial ischemia. About Aeolus Pharmaceuticals Aeolus is developing a variety of therapeutic agents based on its library of 200 proprietary small molecule catalytic antioxidants, with AEOL 10150 being the first to enter human clinical evaluation. AEOL 10150 is a patented, small molecule catalytic antioxidant that has shown the ability to scavenge a broad range of reactive oxygen species, or free radicals. As a catalytic antioxidant, AEOL 10150 mimics and thereby amplifies the body's natural enzymatic systems for eliminating these damaging compounds. Aeolus has completed a Phase I dose escalating safety study of AEOL 10150 in patients diagnosed with Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's disease), which demonstrated that the drug is safe at the tested doses with no serious adverse events, and has to date complete two multiple dose cohorts of a planned three dose- multiple dose study-the completed doses were 40 mg, twice daily (80 mg total per day) for 6 days and a single 40 mg administration on the 7th day, and 60 mg, twice daily (120 mg total per day) for 6 days and a single 60 mg administration on the 7th day. In both cases the drug was safe with no serious adverse events. Because oxygen-derived free radicals are believed to have an important role in the pathogenesis of many diseases, Aeolus' catalytic antioxidants are believed to have a broad range of potential therapeutic uses. The Aeolus Pipeline Initiative, begun in the third calendar quarter of 2005, is an internal development initiative focused on advancing, in addition to AEOL 10150, several of the most promising catalytic antioxidant compounds from Aeolus' proprietary library of 200 compounds. The initial therapeutic focus areas for the Aeolus Pipeline Initiative are: Parkinson's disease; Cystic Fibrosis; Chronic Obstructive Lung Disease; Radioprotection; Tumor Suppression/Bone Marrow Transplantation; and Stroke. These therapeutic focus areas were selected based upon preliminary data developed using Aeolus catalytic antioxidant compounds. The statements in this press release that are not purely statements of historical fact are forward-looking statements. Such statements include, but are not limited to, those relating to Aeolus' product candidates, as well as its proprietary technologies and research programs. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Aeolus' actual results to be materially different from historical results or from any results expressed or implied by such forward- looking statements. Important factors that could cause results to differ include risks associated with uncertainties of progress and timing of clinical trials, scientific research and product development activities, difficulties or delays in development, testing, obtaining regulatory approval, the need to obtain funding for pre-clinical and clinical trials and operations, the scope and validity of intellectual property protection for Aeolus' product candidates, proprietary technologies and their uses, and competition from other biopharmaceutical companies. Certain of these factors and others are more fully described in Aeolus' filings with the Securities and Exchange Commission, including, but not limited to, Aeolus' Quarterly Report on Form 10-Q for the quarter ended December 31, 2005. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Please visit our website at . Aeolus Pharmaceuticals, Inc. CONTACT: Richard P. Burgoon, Jr., Chief Executive Officer of AeolusPharmaceuticals, Inc., +1-949-481-9825 Web site:

Small molecular drug

100 Deals associated with Bucindolol hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D03170	Bucindolol hydrochloride	-	DB12752

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Heart Failure	NDA/BLA	United States	ARCA biopharma, Inc.	-
Atrial Fibrillation	Phase 3	Hungary	ARCA biopharma, Inc.	26 Mar 2014
Myocardial Infarction	Phase 3	Denmark	ARCA biopharma, Inc.	-
Myocardial Infarction	Phase 3	United Kingdom	ARCA biopharma, Inc.	-
Atrial Flutter	Phase 2	United States	ARCA biopharma, Inc.	01 Apr 2014
Atrial Flutter	Phase 2	Canada	ARCA biopharma, Inc.	01 Apr 2014
Atrial Flutter	Phase 2	Hungary	ARCA biopharma, Inc.	01 Apr 2014
Atrial Flutter	Phase 2	Netherlands	ARCA biopharma, Inc.	01 Apr 2014
Atrial Flutter	Phase 2	Poland	ARCA biopharma, Inc.	01 Apr 2014
Atrial Flutter	Phase 2	Serbia	ARCA biopharma, Inc.	01 Apr 2014

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01970501 (GENETIC-AF, CTgov)	Phase 2	Atrial Flutter \| Heart Failure \| Atrial Fibrillation	267	bucindolol hydrochloride (Bucindolol Hydrochloride)	wkpqwqfqjy(suwbqtwopm) = xsmevjjrcc uxqvpiwziz (sxevtxopdw, gsnnlbggca - amxwbneyug) View more	-	15 Sep 2022
				Placebo oral capsule+metoprolol succinate (Metoprolol Succinate)	wkpqwqfqjy(suwbqtwopm) = cxakxauqbh uxqvpiwziz (sxevtxopdw, fplzgrqesj - qclbapuiry) View more
NCT01970501 (GENETIC-AF, Pubmed \| Circ Arrhythm Electrophysiol)	Phase 2	Heart Failure	257	Bucindolol	aotjetywsj(eqmizeefuj) = inghistjxi nqglafiaua (hsbwirctuv, 18.5 - 30.2) View more	-	16 Jul 2021
				Metoprolol	aotjetywsj(eqmizeefuj) = bvvwtwvonj nqglafiaua (hsbwirctuv, 30.0 - 43.5) View more
NCT01970501 (GENETIC-AF, Pubmed) Manual	Phase 2	Heart Failure \| Atrial Fibrillation	267	bucindolol	klmvkflzuz(bzyzbpcyxq) = qimdpaoutl ekohbbfymt (onodyyalyz )	Positive	01 Jul 2019
				metoprolol succinate	klmvkflzuz(bzyzbpcyxq) = fxgnphppsn ekohbbfymt (onodyyalyz )

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