Serelaxin

Eli Lilly is discontinuing a Phase 2 relaxin treatment candidate for heart failure and chronic kidney disease, a spokesperson for the company confirmed to Endpoints News . The drug, an under-the-skin injection known as volenrelaxin, was being tested in an approximately 450-patient trial in people with worsening chronic heart failure who have preserved ejection fraction, or HFpEF. It was also in a Phase 2 chronic kidney disease trial. That study was terminated “due to a lack of foreseeable clinical benefit,” according to an update to the US federal trials database this week. The trial began just three months ago and only enrolled eight patients, versus an original expectation of 280 patients, according to historical records of the trial. A trial of the drug in the EU was stopped in November, according to a European clinical trials database. “Details will be shared at a future medical meeting. No safety concerns were identified,” the Lilly spokesperson said Tuesday afternoon. Volenrelaxin is still listed on the Indianapolis pharma giant’s pipeline page. Many large pharmas will announce shifts to their clinical development plans during quarterly earnings. Lilly’s quarterly update is slated for Feb. 6. The biologic aims to activate the relaxin family peptide receptor 1. The first big program in the space was Novartis’ serelaxin, but it failed a Phase 3 in 2017 . Still in the game are AstraZeneca, with AZD5462 in Phase 2b in chronic heart failure, and Tectonic Therapeutic, which went public last year hoping to break into the space with its mid-stage candidate called TX45. Tectonic’s shares $TECX tanked 40% on Tuesday in an apparent reaction to the news. Its shares had regained about 10% in premarket trading on Wednesday. Leerink Partners analyst David Risinger noted in a Tuesday evening report that Lilly’s candidate “employed a human relaxin analog fused with a serum albumin-binding VHH domain to extend its half-life.” Tectonic’s TX45, meanwhile, uses an Fc-fusion approach that is similar to AstraZeneca’s candidate, Risinger added. The analyst also noted differences in trial endpoints and particular HFpEF patients being studied. Lilly’s work in heart failure also includes a Phase 3 of its obesity and diabetes medication tirzepatide. Last August, the trial showed tirzepatide helped reduce the risk of heart failure in patients with HFpEF. A Phase 1 is also investigating a long-acting “atrial natriuretic peptide” for heart failure. Retatrutide, its so-called “triple G” candidate for cardiometabolic health, is also being tested in patients with chronic kidney disease. Editor’s note: This story was updated to include stock reaction and information from an analyst note.

WATERTOWN, Mass., Dec. 03, 2024 (GLOBE NEWSWIRE) -- Tectonic Therapeutic, Inc. (NASDAQ: TECX) (“Tectonic”) a clinical stage biotechnology company focused on the discovery and development of therapeutic proteins and antibodies that modulate the activity of G-protein coupled receptors (“GPCRs”), today announced it will host a virtual key opinion leader (KOL) event on Thursday, December 12, 2024 from 4:00 PM to 6:00 PM ET. To register, click here. Key opinion leaders will include John R. Teerlink, MD, FHFSA (University of California San Francisco) and Raymond L. Benza, MD, FACC, FAHA, FACP (Icahn School of Medicine at Mount Sinai), who will discuss the unmet medical need and current treatment landscape for patients with Group 2 Pulmonary Hypertension due to Heart Failure with Preserved Ejection Fraction (Group 2 PH-HFpEF). The event will focus on Tectonic’s lead program, TX45, an investigational Fc-relaxin fusion protein with optimized pharmacokinetics and biophysical properties that activates the RXFP1 receptor, the GPCR target of the hormone relaxin. TX45 is being evaluated in patients with Group 2 PH-HFpEF in an ongoing Phase 1b hemodynamic proof-of-concept study and a Phase 2 clinical proof-of-concept study. A live question and answer session will follow the formal presentations. About the Key Opinion Leaders: Professor John R. Teerlink, MD, FACC, FAHA, FESC, FHFA, FHFSA, FRCP (London)Professor Teerlink is Professor of Medicine at the University of California San Francisco (UCSF). After graduating from Swarthmore College with a Religion major, he received an MD from Harvard Medical School and completed his Internal Medicine residency and Cardiovascular Medicine fellowship at UCSF, as well as post-doctoral fellowships in Cardiovascular pharmacology (Hoffman-LaRoche; Basel, Switzerland), echocardiography (UCSF) and heart failure (UCSF-affiliated hospital). He is actively involved in the design and execution of many heart failure clinical trials, serving on endpoint, data monitoring, steering and executive committees for numerous international studies investigating a variety of new pharmacologic therapies, as well as stem cell and gene therapies, diagnostic modalities and other devices. He was the lead clinical investigator for the serelaxin development program, serving as Principal Investigator for Pre-RELAX-AHF, RELAX-AHF, RELAX-AHF-2 and RELAX-Repeat, and as a steering committee member for RELAX-AHF-Asia. Dr. Teerlink has served on the US FDA Cardiovascular and Renal Drug Advisory Committee, as well as on other FDA drug, device, diagnostics, and vaccine panels and serves as a consultant on pre-clinical and clinical development programs in multiple areas of cardiology, as well as in non-cardiovascular indications. Dr. Teerlink was a founding physician member of the American Association of Heart Failure Nurses and is a Past President of the Heart Failure Society of America. He was an Associate Editor for the Journal of Cardiac Failure, Guest Editor-in-Chief and Associate Editor for JACC: Heart Failure, and is a clinical scholar presenting many lectures and over 300 publications, including a chapter on Acute Heart Failure in Braunwald’s Heart Disease textbook. He was profiled in The Lancet as an internationally recognized leader in heart failure. Raymond L. Benza, MD, FACC, FAHA, FACPDr. Benza is a Professor and System Director of Pulmonary Hypertension at the Icahn School of Medicine at Mount Sinai, Mount Sinai Fuster Heart Hospital. He is a fellow of the American College of Physicians, the American Heart Association Council on Clinical Cardiology, the American College of Chest Physicians and the American College of Cardiology. He is a diplomat of the American Board of Internal Medicine with certification in the subspecialties of cardiovascular diseases and advanced heart failure and transplantation. Dr. Benza currently holds administrative positions in the Pulmonary Vascular Research Institute and the International Society of Heart and Lung Transplantation and is the former treasurer of that society. He served on President Barak Obama’s Advisory Committee on Organ Transplantation (ACOT) in the Health Resources and Services Administration for 4 years and was knighted in 2015 by his Royal Highness Vittorio Emanuele of Italy for his philanthropic work in patients with pulmonary arterial hypertension and was admitted to the Association of University Cardiologists. He sits on multiple journal editorial committees and is the Steering Committee Chair for several industry trials in PAH. His primary clinical interests are the evaluation and treatment of advanced congestive heart failure, cardiac transplantation, and pulmonary arterial hypertension (PAH). He participates in major clinical studies of new therapies for the treatment of heart failure, mechanical support, and pulmonary hypertension. Dr. Benza is a funded investigator for the National Institutes of Health and the American Heart Association for his work in pulmonary arterial hypertension focusing on risk stratification, pharmacogenomics and new device therapies for this disease state. About TX45, a long-acting Fc-relaxin fusion proteinTX45 is an investigational Fc-relaxin fusion protein with optimized pharmacokinetics and biophysical properties that activates the RXFP1 receptor, the G-protein coupled receptor target of the hormone relaxin. Relaxin is an endogenous protein, expressed at low levels in both men and women that is a pulmonary and systemic vasodilator with lusitropic, anti-fibrotic and anti-inflammatory activity. In normal human physiology, relaxin is upregulated during pregnancy where it exerts vasodilative effects, reduces systemic and pulmonary vascular resistance and increases cardiac output to accommodate the increased demand for oxygen and nutrients from the developing fetus. Relaxin also exerts anti-fibrotic effects on pelvic ligaments to facilitate delivery of the baby. About Group 2 Pulmonary Hypertension in HFpEFThe World Health Organization has defined five groups of pulmonary hypertension (“PH”). Tectonic is focused on the Group 2 subtype, a condition that develops due to left-sided heart disease, specifically pulmonary hypertension secondary to left heart failure with preserved ejection fraction (“PH-HFpEF”). In patients with PH-HFpEF, chronic heart failure leads to increased blood pressure in the pulmonary arteries, exerting severe strain on the right side of the heart, which adapts poorly to the increased pressure. This increased pulmonary pressure gradually causes worsening exercise capacity, shortness of breath and right-sided heart failure which can lead to death. Although several Group 1 PH (Pulmonary Arterial Hypertension, PAH) medications have been explored in Group 2 PH, to date, no medications have been approved for its treatment. About TectonicTectonic is a biotechnology company focused on the discovery and development of therapeutic proteins and antibodies that modulate the activity of G-protein coupled receptors (“GPCRs”). Leveraging its proprietary technology platform called GEODe™ (GPCRs Engineered for Optimal Discovery), Tectonic is focused on developing biologic medicines that overcome the existing challenges of GPCR-targeted drug discovery and harness the human body to modify the course of disease. Tectonic focuses on areas of significant unmet medical need, often where therapeutic options are poor or nonexistent, as these are areas where new medicines have the potential to improve patient quality of life. Tectonic is headquartered in Watertown, Massachusetts. For more information, please visit www.tectonictx.com and follow on LinkedIn. Forward-Looking StatementsThis press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. All statements in this press release other than statements of historical facts are “forward-looking statements. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include statements regarding: the design, objectives, initiation, timing, progress and results of clinical trials of Tectonic’s product candidates, including the ongoing Phase 1b and Phase 2 clinical trials for TX45 in Group 2 PH-HFpEF; and the potential properties and benefits of TX45. These forward-looking statements are based on Tectonic’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause Tectonic’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Many factors may cause differences between current expectations and actual results, including: the potential that success in preclinical testing and earlier clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate; the impacts of macroeconomic conditions, including the conflict in Ukraine and the conflict in the Middle East, heightened inflation and uncertain credit and financial markets, on Tectonic’s business, clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; Tectonic’s ability to realize the benefits of its collaborations and license agreements; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause Tectonic’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified under the heading “Risk Factors” in Tectonic’s quarterly report on Form 10-Q filed with the SEC on November 12, 2024, and in other filings that Tectonic makes and will make with the SEC in the future. Tectonic expressly disclaims any obligation to update any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. For more information, please visit www.tectonictx.com and follow on LinkedIn. Source: Tectonic Therapeutic