SK channel

AP30663 achieved proof of mechanism with first-in-class SK channel inhibition compound in atrial fibrillation – primary endpoint met: 99.9% probability of superiority over placebo AP31969, a novel compound being developed for sinus rhythm maintenance in atrial fibrillation, commences dosing in phase 1 COPENHAGEN, Denmark, Dec. 13, 2023 /PRNewswire/ -- Acesion Pharma ("Acesion" or "the Company"), a biotech company pioneering first-in-class novel therapies for atrial fibrillation ("AF"), the most common cardiac arrhythmia, today announces the publication of data in Nature Medicine with the full results from its Phase 2 proof-of-concept trial of AP30663, a first-in-class SK ion channel inhibitor for conversion of AF to normal sinus rhythm. As previously announced, the trial met its primary endpoint, thereby demonstrating the first ever proof mechanism for SK channel inhibition as a novel treatment for AF. AP30663 Phase 2 trial results In the trial, patients with a current episode of AF lasting for seven days or less were randomized to receive an intravenous infusion of 3 or 5 mg/kg of AP30663 or placebo. The primary endpoint of the trial was cardioversion from AF to sinus rhythm within 90 min from the start of the intravenous infusion, analysed using Bayesian statistics. The primary endpoint occurred in 42% (5 of 12), 55% (12 of 22) and 0% (0 of 25) of patients treated with 3 mg/kg AP30663, 5 mg kg/1 AP30663, or placebo, respectively. Both doses demonstrated more than 99.9% probability of superiority over placebo, surpassing the prespecified 95% threshold. No ventricular arrhythmias were observed, and adverse event rates were comparable between active and placebo group. The results are now published in the high-impact journal Nature Medicine (). AP31969 Phase 1 trial initiated In addition to the publication of the above phase 2 trial results, the company has also successfully dosed the first healthy volunteer subjects in a phase 1, first-human-dose, clinical trial of AP31969, an oral first-in-class SK ion channel inhibitor designed to maintain sinus rhythm in patients suffering from AF. The phase 1 trial is planned to consist of two parts: single ascending dose and multiple ascending dose. In addition, the effect of food on the absorption of the compound will be investigated. Results from the trial are expected in Q3 2024. AP31969 is being developed for chronic oral maintenance treatment to prevent AF recurrence (maintain sinus rhythm) and has shown strong pre-clinical efficacy combined with a promising safety profile. Anders Gaarsdal Holst, MD, PhD, Chief Executive Officer of Acesion, said "We are pleased that Nature Medicine has recognised the importance of our AP30663 results for conversion of AF to sinus rhythm and accepted them for publication in their prestigious journal. Based on this achievement of clinical proof-of-mechanism, and enabled by our recent successful Series B financing, we have now also moved our oral SK inhibitor AP31969 into clinical development. Through this study, we will learn about the safety, as well as the pharmacokinetics of AP31969 and it is an important step towards addressing the large unmet need within atrial fibrillation." AF is the most common type of cardiac arrhythmia and is forecast to affect 25 million people in the US and EU by 2030. Existing drug therapies for AF are associated with the risk of serious cardiac or other adverse effects, resulting in a great need for safer drugs. Yet, there has been a lack of innovation and development with no new chronic AF drug approved for nearly 20 years. With AP31969, Acesion is aiming to develop a safer alternative. About Acesion Pharma Acesion builds on 20 years of know-how with development of small-molecule SK inhibitors and is the world leader in the field of SK channel inhibition, being the only company able to identify and progress SK channel inhibitors into clinical trials. In pre-clinical studies, inhibiting the SK channels has been shown to result in pronounced antiarrhythmic effects in the atria while avoiding effects on the ventricles, the major chambers of the heart and the source of most safety issues with existing drugs. Furthermore, the SK channel has strong genetic validation, with genes encoding the SK channels having one of the strongest associations to AF in human genome-wide association studies. Acesion's AP30663 IV is a short acting conversion therapy that has completed a phase 2 trial proving the value of this first-in-class mechanism in AF and thereby de-risking Acesion's broader SK inhibitor pipeline. Acesion's oral program with lead candidate AP31969 is designed and engineered using in house knowhow to optimise for, and meet, very high hurdles in both efficacy and particularly safety where existing treatments fall short of patient needs. Acesion Pharma is backed by Novo Holdings, Canaan, Alpha Wave Ventures, Global BioAccess Fund, Wellcome Trust, Broadview Ventures and FC Capital. About atrial fibrillation (AF) AF is the most common type of cardiac arrhythmia mainly affecting the elderly population. Lifetime risk for development of AF is estimated at more than one in three. It is forecast to affect 25 million people in the US and EU by 2030. AF is characterized by chaotic electrical activity in the upper chambers of the heart, the atria, resulting in an irregular and high heart rate. AF is associated with impaired quality of life, increased rate of hospitalization, and a five-fold increased risk of stroke. Increasing evidence suggests that patients with AF also face a higher risk of cognitive dysfunction and dementia. AF is often treated by electrical shock to bring the heart back to its normal rhythm (conversion). This requires general anesthesia in a hospital setting. In addition, many patients are likely to benefit from chronic treatment to prevent AF and maintain normal sinus rhythm. Existing drug therapies for cardioversion or prevention of AF are associated with risk of serious cardiac or other adverse effects, resulting in a great need for safer drugs. Yet, there has been a lack of innovation and development with no new chronic AF drug approved for nearly 20 years. A landmark New England Journal of Medicine published clinical trial () has shown that sinus rhythm maintenance treatment improves survival and long-term outcomes for AF patients. SOURCE Acesion Pharma

The lung disease Idiopathic pulmonary fibrosis (IPF) has few available treatments, and that medical need has drawn research interest from big pharmaceutical companies and smaller biotechs. Avalyn Pharma’s approach is a new twist on two older drugs and it has raised $175 million for clinical testing. In IPF, scar tissue called fibrosis forms in the lungs. The chronic disorder leads to worsening breathing problems that become fatal within three to five years of diagnosis. The two FDA-approved IPF therapies, nintedanib and pirfenidone, don’t cure the disease but they can slow its progression. However, these small molecules are taken as capsules. Circulating throughout the body, they spark side effects such as nausea, rash, sensitivity to light, and weight loss. These tolerability issues lead many patients to stop using the drugs. Avalyn aims to improve on nintedanib and pirfenidone with inhalable versions that keep the effects of both drugs targeted to the lungs. The Seattle-based company has published data from a Phase 1 test of APO1, an inhalable version of pirfenidone, showing improved tolerability and lung function compared to oral formulations of the drug. Avalyn has also said APO2, its inhaled version of nintedanib, was well tolerated in a Phase 1 test that enrolled healthy volunteers and IPF patients. “Fewer than 30% of patients in the U.S. are treated with either of the two approved oral medicines today due to their significant tolerability challenges,” Avalyn CEO Lyn Baranowski said in a prepared statement. “There is an urgent need for effective treatments that patients can tolerate, which we believe can be addressed with inhaled delivery.” With the new capital, Avalyn plans to advance APO1 into a Phase 2b study and APO2 into a Phase 2a test. Avalyn’s Series C financing was co-led by Perceptive Xontogeny Venture Funds, SR One, and Eventide Asset Management. They were joined by new investors, Vida Ventures, Wellington Management, Rock Springs Capital, funds and accounts advised by T. Rowe Price Associates, Surveyor Capital, Catalio Capital Management, and Piper Heartland. Current investors, including Novo Holdings A/S, Norwest Venture Partners, F-Prime Capital, Pivotal bioVenture Partners, and RiverVest Venture Partners, also participated. With the third quarter of 2023 now closed, here’s a look back at some other recent biotech financings. —Protein design company Evozyne raised $81 million to support its generative AI-powered drug discovery technology. Chicago-based Evozyne has partnerships with Takeda Pharmaceutical and Nvidia. Fidelity Management & Research Company and OrbiMed led the Series B round, which also included the participation of NVentures, the venture capital arm of Nvidia. —Cancer screening and detection startup Harbinger Health closed a $140m Series B financing. Planned uses of the funding include the completion of a 10,000 participant clinical study of its blood-based cancer screening platform. —Hyku Biosciences launched with $56 million to support its research developing precision covalent cancer drugs that target amino acids such as histidines, tyrosines, and lysines. The startup was incubated in RAVen, the company creation engine of RA Capital Management. That venture capital firm was joined by Droia Ventures and Novartis Venture Fund in leading Hyku’s seed financing. Lexington, Massachusetts-based Hyku joins a growing number of startups working to expand covalent cancer drugs beyond the targeting of the amino acid cysteine. —ReCode Therapeutics added $50 million to its Series B financing, bringing the round’s total to $260 million. New investors include BLV Ventures and Solasta Ventures. Menlo Park, California-based ReCode is developing genetic medicines with a platform technology that can target the delivery of a therapy to particular tissue type. ReCode is preparing for Phase 1 testing of a therapy for primary ciliary dyskinesia as well as an investigational new drug application for a cystic fibrosis therapeutic candidate. ReCode’s Series B round was initially $80 million raised nearly two years ago. —RNA-editing therapies developer AIRNA launched with $30 million in financing. The startup says its approach delivers a safe oligonucleotide programmed to recruit an endogenous cellular enzyme, ADAR, to introduce a precise RNA modification, which results in changes to encoded therapeutic proteins. While the company aims to develop therapies for common diseases, its first target is the rare inherited genetic disease alpha-1 antitrypsin deficiency. AIRNA’s financing was led by Arch Venture Partners. —Molecular glue startup Magnet Biomedicine launched with $50 million in financing. The Boston company’s technology discovers small molecules that prompt “cooperative interaction” between proteins. Magnet’s Series A round was led co-led by Newpath Partners and Arch Venture Partners. —Acesion Pharma’s lead program is a potentially safer treatment for atrial fibrillation. The Copenhagen, Denmark-based has raised €45 million to bring that drug candidate, AP31969, to its first test in humans. The small molecule is an SK ion channel inhibitor. With the Series B financing, co-led by Canaan and Alpha Wave, Acesion said it has sufficient capital to support AP31969 through completion of Phase 2 testing. —AbolerIS Pharma, a startup developing drugs for autoimmune diseases, raised €27.3 million as it prepares to advance its lead program to clinical testing. The antibody drug targets CD45RC, protein expressed on a subset of T cells and has potential application as a treatment for patients whose rheumatoid arthritis does not respond to standard of care drugs. The Belgian company’s Series A financing was led by Caixa Capital Risc and co-led by Sound Bioventures and earlier investor Newton Biocapital. —Generate BioMedicines raised $273 million in Series C financing to support a lead SARS-CoV-2 program and other programs on track to reach human testing in the next two years. Somerville, Massachusetts-based Generate uses generative artificial intelligence to analyze known proteins and make predictions about the targets these proteins will bind to and their subsequent therapeutic effect. Generate currently has 17 programs and expects the new funding will enable it to start 10 new programs annually. Generate last raised money in 2021, a $370 million Series B round of funding. To date, the company says its financing haul totals nearly $700 million. The latest financing attracted new investors including Amgen, NVentures, MAPS Capital, and Pictet Alternative Advisors.

Financing co-led by new investors Canaan and Alpha Wave, and with participation by the Global BioAccess Fund and existing investor Novo Holdings COPENHAGEN, Denmark, Sept. 26, 2023 /PRNewswire/ -- Acesion Pharma ('Acesion' or 'the Company'), a biotech company pioneering first-in-class novel therapies for atrial fibrillation ('AF'), the most common cardiac arrhythmia, today announces that it has successfully closed an oversubscribed €45M Series B financing round. The equity financing was co-led by new US-based investors Canaan and Alpha Wave and with participation by the Global BioAccess Fund, as well as existing investor Novo Holdings. The financing will be used to advance the clinical development of AP31969, an SK ion channel inhibitor optimised for chronic oral treatment of AF. Earlier this year, Acesion demonstrated clinical proof-of-concept with AP30663, its first-in-class SK ion channel inhibitor for conversion of AF to normal sinus rhythm. AP31969 will be developed for chronic oral maintenance treatment to prevent AF recurrence. Following the successful Series B financing, Acesion is well capitalised to progress AP31969 into a phase 1 and completion of a phase 2 trial. AF is the most common type of cardiac arrhythmia and is forecast to affect 25 million people in the US and EU by 2030. Existing drug therapies for AF are associated with the risk of serious cardiac or other adverse effects, resulting in a great need for safer drugs. Yet, there has been a lack of innovation and development with no new chronic AF drug approved for nearly 20 years. With AP31969, Acesion is aiming to develop a safer alternative. In connection with the closing of the financing, the composition of the Acesion board of directors will change to include Tim Shannon, General Partner at Canaan, and Nik Economopoulos, Analyst from Alpha Wave. Jørgen Søberg Petersen, Partner at Novo Holdings, will remain Chairman. Anders Gaarsdal Holst, MD, PhD, Chief Executive Officer of Acesion, said, "The high levels of investor interest and demand that we saw during this financing speak to the strong data we have generated, both on the novel mechanism of SK channel inhibition in general and the AP31969 compound specifically. This is a powerful endorsement for our team and the quality of our science. With the financing in hand, we are focused on progressing AP31969 into a phase 1 clinical trial later this year." Tim Shannon, MD, General Partner in Canaan, said, "Acesion is redefining treatment for patients suffering from atrial fibrillation. The impressive preclinical data from AP31969 shows great promise and we are delighted to support Acesion in taking AP31969 through to Phase 2 completion." Jørgen Søberg Petersen, MD, PhD, MBA, Partner in Novo Holdings, said, " As the founding and largest shareholder, Novo Holdings remains committed in helping Acesion realise the full potential of AP31969. The preclinical data is encouraging and with this series B financing in place Acesion will be able to progress the development to the important milestone of completing a phase 2 trial and thereby being ready for phase 3 programme." About Acesion Pharma Acesion builds on 20 years of know-how with development of small-molecule SK inhibitors and is the world leader in the field of SK channel inhibition, being the only company able to identify and progress SK channel inhibitors into clinical trials. In pre-clinical studies, inhibiting the SK channels has been shown to result in pronounced antiarrhythmic effects in the atria while avoiding effects on the ventricles, the major chambers of the heart and the source of most safety issues with existing drugs. Furthermore, the SK channel has strong genetic validation, with genes encoding the SK channels having one of the strongest associations to AF in human genome-wide association studies. Acesion's AP30663 IV is a short acting conversion therapy for hospitals that has completed a phase 2 trial proving the value of this first-in-class mechanism in AF and thereby de-risking Acesion's broader SK inhibitor pipeline. Acesion's oral program is designed and engineered using in house knowhow to optimise for, and meet, very high hurdles in both efficacy and particularly safety where existing treatments fall short of patient needs. Acesion Pharma is backed by Novo Holdings A/S, Canaan, Alpha Wave Alpha Wave Ventures, Global BioAccess Fund, Wellcome Trust, Broadview Ventures and FC Capital. About Canaan Canaan is an early-stage venture capital firm that invests in entrepreneurs with visionary ideas. With $6.8 billion under management, a diversified fund, and hundreds of exits to date, Canaan partners with entrepreneurs building the next generation of technology and healthcare companies that will transform how we live, work, and thrive. To learn more about our people and our portfolio, please visit: About Alpha Wave Alpha Wave is a global investment company that manages a variety of partnerships that separately focus on three main verticals: private equity (venture and growth), credit, and public markets. It is led by Rick Gerson, Navroz Udwadia, and Ryan Khoury. Alpha Wave has offices in New York, Miami, London, Monaco, Madrid, Abu Dhabi, Tel Aviv, Bangalore, Jakarta, and Sydney. Its flagship global venture and growth fund, Alpha Wave Ventures, aims to invest in best-in-class venture and growth-stage companies and endeavors to be helpful long-term partners to the founders and management teams. For more information, please visit . About the Global BioAccess Fund The Global BioAccess Fund invests in companies developing novel therapeutics and devices to address serious unmet medical needs in oncology, cardiovascular, neurological, and rare diseases. Leveraging the deep life sciences expertise and global reach of its management, scientific advisors, and partners, the Global BioAccess Fund actively supports ventures who are in clinical-stage development, including IND enabling studies and clinical trials. See . About Novo Holdings Novo Holdings is a holding and investment company that is responsible for managing the assets and the wealth of the Novo Nordisk Foundation. The purpose of Novo Holdings is to improve people's health and the sustainability of society and the planet by generating attractive long-term returns on the assets of the Novo Nordisk Foundation. Wholly owned by the Novo Nordisk Foundation, Novo Holdings is the controlling shareholder of Novo Nordisk A/S and Novozymes A/S and manages an investment portfolio with a long-term return perspective. In addition to managing a broad portfolio of equities, bonds, real estate, infrastructure and private equity assets, Novo Holdings is a world-leading life sciences investor. Through its Seeds, Venture, Growth, and Principal Investments teams, Novo Holdings invests in life science companies at all stages of development. As of year-end 2022, Novo Holdings had total assets of EUR 108 billion. About atrial fibrillation (AF) AF is the most common type of cardiac arrhythmia mainly affecting the elderly population. Lifetime risk for development of AF is estimated at more than one in three. It is forecast to affect 25 million people in the US and EU by 2030. AF is characterized by chaotic electrical activity in the upper chambers of the heart, the atria, resulting in an irregular and high heart rate. AF is associated with impaired quality of life, increased rate of hospitalization, and a five-fold increased risk of stroke. Increasing evidence suggests that patients with AF also face a higher risk of cognitive dysfunction and dementia. AF is often treated by electrical shock to bring the heart back to its normal rhythm (conversion). This requires general anesthesia in a hospital setting. In addition, many patients are likely to benefit from chronic treatment to prevent AF and maintain normal sinus rhythm. Existing drug therapies for cardioversion or prevention of AF are associated with risk of serious cardiac or other adverse effects, resulting in a great need for safer drugs. Yet, there has been a lack of innovation and development with no new chronic AF drug approved for nearly 20 years. A landmark New England Journal of Medicine published clinical trial () has shown that sinus rhythm maintenance treatment improves survival and long-term outcomes for AF patients. SOURCE Acesion Pharma