β2-adrenergic receptor

Expands Adrenergic Pipeline to Address Neurogenic Orthostatic Hypotension and Major Depressive Disorder in Older Adults SAN CARLOS, Calif.--(BUSINESS WIRE)--CuraSen Therapeutics, Inc., a clinical-stage biopharmaceutical company developing oral, rapid onset, small molecule drugs to treat psychiatric and neurodegenerative diseases, announced today that it has appointed Kathleen Sereda Glaub, MBA, formerly executive chair, as chief executive officer. Dr. Anthony Ford will move to the role of president and chief scientific officer, and continue to lead research and development. Patrick Enright, managing director of Longitude Capital, will become chair of the board. Along with these executive changes, the company announced clinical program updates for its drug candidates that are each designed to restore adrenergic stimulus that declines with age or disease. CuraSen’s most recent development candidate is CuraAX (CST-3056), an alpha-1A adrenoceptor (α 1A -AR) agonist being developed as a treatment for neurogenic orthostatic hypotension (nOH). The company is planning to submit an investigational new drug (IND) application this quarter. A significant orphan indication affecting approximately 120,000-150,000 patients in the U.S., nOH is a dysfunction in the autonomic nervous system common in Parkinson’s disease (PD) and related diseases that causes sudden drops in blood pressure upon standing. This can lead to debilitating dizziness, weakness, cognitive decline and dangerous falls. CuraAX is a selective, CNS-penetrant, α 1A -AR agonist designed to provide cognitive benefit as well as control harmful blood pressure deviations. CuraCN (formerly known as CST-103/CST-107), a beta2 adrenoceptor (β 2 -AR) agonist combination, is targeted for a Phase 2b study in major depressive disorder in adults 65 and older, many of whom also suffer from cognitive decline. These plans are based on the company’s previous Phase 2 clinical study in patients that revealed compelling evidence of anti-depressant efficacy and improvements in cognition tests. CuraXN (formerly known as CST-2032/CST-107), a second β 2 -AR agonist combination, is in development for Alzheimer’s disease (AD) to address both cognitive symptoms and disease progression. All three drug candidates work by restoring adrenergic function that declines with age and, in particular, is lost early in neurodegenerative diseases such as AD & PD. CuraSen’s development candidates have strong potential to improve cognitive function and mood, in addition to addressing specific aspects of disease pathobiology. “We are thrilled to have Ms. Glaub assume the role of chief executive officer as CuraSen seeks to capitalize on the company’s adrenergic platform and clinical data to develop a broad pipeline of drugs for psychiatric and neurodegenerative diseases. These include opportunities for a significant, fast-to-market, orphan opportunity in neurogenic orthostatic hypotension,” said Mr. Enright, board chair. “CuraSen will benefit from the collective and complementary executive experience of both Ms. Glaub and Dr. Ford, both co-founders of the company.” Ms. Glaub brings more than 30 years of experience in biopharmaceutical corporate development, strategy, financing and company-building. She serves on the board of directors of IO Biotech, and previously served on the boards of Codexis, Aligos Pharmaceuticals and Escient Pharmaceuticals. Ms. Glaub was previously chief executive officer of Afferent Pharmaceuticals, which was acquired by Merck in 2016 for $1.25 billion. Under her leadership, the company advanced gefapixant to Phase 3 readiness for the treatment of chronic cough and raised $80 million in additional private funding for Afferent. Previously, she served as president of Plexxikon, and helped develop two FDA-approved drugs, Zelboraf® for metastatic melanoma and Turalio® for tenosynovial giant cell tumor (TGCT). She led Plexxikon’s business and financing strategy, negotiated multimillion-dollar partnerships, and led the sale of the company to Daiichi Sankyo for nearly $1 billion. She previously held positions as senior vice president and chief financial officer of Cell Genesys, treasurer of Genentech, and various finance and treasury roles with Intel Corporation. Ms. Glaub received her BA from the University of California, Berkeley, and her MBA from Northwestern University. “CuraSen’s expertise in adrenergic pharmacology, chemistry and clinical development has led to the discovery of three promising drug candidates focused on some of the most debilitating and common neurodegenerative and psychiatric diseases affecting patients and their families. Our adrenergic target mechanisms are already validated by approved drugs in a range of indications, and we have confirmed the ability to develop CNS-penetrant compounds with a unique approach to safety,” said Glaub. “Given the strong and rapid-onset efficacy signals pointing to an anti-depressant effect in our past studies and our understanding of adrenergic deficits in older adults, we believe there is a unique opportunity to address depression in these patients with CuraCN. With CuraXN, we hope to deliver a transformational treatment for Alzheimer’s disease with our holistic approach to restoring brain functionality and health. Lastly, with CuraAX, we believe we can offer major advantages over current treatments for nOH, including durability of efficacy and cognitive benefit, dosing convenience and improved safety.” About CuraSen Therapeutics CuraSen is focused on the development of new treatments for psychiatric and neurodegenerative diseases, including neurogenic orthostatic hypotension, major depressive disorder and Alzheimer’s disease. CuraSen’s drugs are small molecule, oral tablets designed to activate certain receptor populations in the brain to compensate for decline of the adrenergic system driven by aging and disease. The company has evaluated two β 2 -AR agonist candidates, CuraCN and CuraXN, in multiple Phase 2 clinical studies for effects on memory, attention, executive function and mood, as well as safety and tolerability. CuraSen is planning to submit an IND application by the end of 2024 for its third drug candidate CuraAX, an α 1A -AR agonist, for the treatment of nOH. For more information, please visit . Contacts Susan Kinkead Kinkead Communications susan@kinkeadcomm.com 415-509-3610

This dose escalation study for safety and tolerability of clenbuterol incorporates Springbok's precision muscle MRI analysis and molecular outcome measures CHARLOTTESVILLE, Va., June 12, 2024 /PRNewswire/ - Springbok Analytics (), a life sciences muscle analytics company, announced today its participation in a Phase 1 Clinical Trial to evaluate safe dosage for clenbuterol as a treatment for Facioscapulohumeral muscular dystrophy (FSHD). Springbok's MRI-based muscle analysis helps researchers to better understand and identify disease progression of FSHD by providing individual muscle volume and fat fraction metrics in trial participants. Beyond studying the safety and tolerability of clenbuterol, Springbok is focused on strengthening and extending the foundations for future FSHD clinical trial design and execution. Springbok is also supporting the 31st Annual FSHD Society International Research Congress held this week in Denver. This trial is part of a larger NIH Wellstone grant led by Jeff Chamberlain, MD and Stephen Tapscott, MD, PhD, with trial activities coordinated by Jeffrey M. Statland, MD and Rabi Tawil, MD, who direct the FSHD Clinical Trials Research Network (CTRN) out of the University of Kansas and the University of Rochester, respectively. Seth Friedman, PhD at Seattle Children's is overseeing imaging implementation. "We are excited to expand the scope of our work with Springbok Analytics. This technology can benefit an FSHD-focused clinical trial by giving us new perspectives on what can be modulated by drug therapy," said Dr. Friedman. "The shorter exam duration will improve patient tolerability and Springbok's comprehensive individual muscle analytics get us closer to deriving personalized progression models." FSHD is one of the most prevalent muscular dystrophies, affecting an estimated 20,000 people in the United States alone. There are currently no FDA approved therapies for FSHD, which represents both a large and unmet medical need. Clenbuterol has been shown to decrease DUX4-related targets in patient-derived FSHD cell assays, and several small studies in neuromuscular disorders have demonstrated improved strength or function with clenbuterol. Springbok's AI advancements have also led to improvements in both imaging and processing time. A recent study focused on the disease burden of FSHD clinical trial participants1 highlighted a strong preference for imaging over invasive muscle biopsies, which often remove healthy muscle tissue, as well as the need to reducing imaging time. 85 percent of the FSHD patients surveyed said that they would be willing to take part in MRI, compared to just 44 percent for an open muscle biopsy. For participants that indicated they would be willing to undergo an MRI, just 30 percent said they would be willing to sit in an MRI machine for two hours or more. Springbok's full body analysis can be done in under 40 minutes, and its protocols have been designed with scalability in mind, knowing that flexibility and ease-of-deployment are requirements across global multi-site studies. "The rationale for this trial is that if clenbuterol is safe and well tolerated, and can increase muscle mass and reduce DUX4 levels, it can be repurposed to both stop disease progression and restore motor function," said Jeffrey M. Statland, MD, professor of neurology at the University of Kansas Medical Center. "Springbok's precision and sensitivity are so important in studying a disease like FSHD, which impacts the form and function of individuals, and their specific muscles, so differently." Springbok scans are also accompanied by patient-facing reports with 3D muscle visualizations, empowering individuals to better manage their muscle health and disease progression. "The patient experience in clinical trials is always important, especially when there are accessibility issues. From what we have heard from many FSHD patients, length of time in the scanner and lack of reporting are factors of consideration in trial participation," said Scott Magargee, Springbok Analytics Co-Founder and CEO. "We are helping researchers and pharmaceutical companies to run more effective clinical trials by generating more precise and personalized insights, supporting those on the leading edge of FSHD research pursuing improved treatments, and ultimately, a cure." Springbok's flexible imaging protocol has been implemented at hundreds of imaging centers around the world and is compatible across all major scanner platforms. The company is also developing standardized guidance for how to use muscle MRI as a trial passport to screen for drug trial enrollment. The FSHD Clinical Trial Research Network (CTRN) is being leveraged as part of this trial, and the data is intended to ultimately support a Phase 3 trial to confirm the efficacy of Clenbuterol in FSHD. To learn more about Springbok's muscle analysis capabilities for clinical trials, visit here. About Springbok Analytics: Springbok is a life sciences muscle analytics company that drives better health and performance outcomes. Its technology analyzes MRI data and creates personalized 3D visualizations of muscle health, enhancing the assessment, treatment monitoring, research and diagnostic value of advanced imaging. Springbok's rapid imaging sequence and AI-based analysis reveals a complete view of musculoskeletal health, precisely quantified individual muscle volume and quality, fat infiltration, left-right asymmetries, as well as scar tissue, edema, and tendon morphology. To learn more about how Springbok is creating a better view of health, please visit . SOURCE Springbok Analytics

Preclinical data shows precision modulation of beta-2 and beta-3 signaling boosts metabolism and enhances body recomposition STOCKHOLM, Sweden, May 24, 2024 (GLOBE NEWSWIRE) -- Atrogi, a pioneering clinical-stage biotech company advancing treatments for metabolic disorders, announces a publication in the Journal of Molecular Metabolism (1). The research paper validates the mechanism of action of the company’s first-in-class, small molecule, ATR-127, in combating obesity and metabolic complications. Unlike existing anti-obesity therapies that compromise lean muscle mass, ATR-127 induces significant weight loss while preserving crucial lean body mass. ATR-127 binds to both the beta-2 and beta-3 adrenergic receptors in a unique manner, allowing for precise modulation of downstream signaling cascades. Unlike conventional approaches, ATR-127's innovative binding mechanism enables selective activation of specific signaling pathways. This unlocks the full therapeutic potential of beta-2 and beta-3 receptor agonism, maximizing beneficial effects on metabolism and body composition while mitigating the cardiovascular side effects commonly associated with indiscriminate receptor activation. Atrogi’s CEO, Alexandra Ekman Ryding, said, “This publication highlights strong pre-clinical data relating to ATR-127 and validates our approach for the development of a novel modality for the treatment of obesity. We are now advancing our next generation small molecules for the treatment of obesity to IND preparatory studies in H1 next year and expect to enter the clinic in 2026.” Atrogi´s founder and CSO, Tore Bengtsson, a Professor of Physiology at Stockholm University, said, “There is a high demand for novel treatments of obesity without the current debilitating side effects and muscle loss. We believe our pioneering dual receptor beta-agonist approach has the potential to transform the obesity treatment landscape. Our vision is for a more holistic treatment for diabesity and steatohepatitis that not only treats the underlying cause of disease but also supports overall health and quality of life.” The study found that ATR-127 enhances energy expenditure and promotes beneficial metabolic changes by inducing skeletal muscle glucose uptake and the concomitant activation of brown and beige adipose tissue. This results in healthy weight loss - decreasing fat mass but preserving muscle, whilst reducing hepatic inflammation and lipid content. ATR-127’s ability to deliver precise signaling modulation prevents excessive cAMP production thereby lowering cardiac force production and mitigating risks of cardiovascular side effects. This study was a collaborative international effort involving Atrogi AB, and institutions in Europe and Australia, including Stockholm University, Monash University, University of Nottingham, Karolinska Institute, Maastricht University Medical Center, Latvian Institute of Organic Synthesis, Excellerate Bioscience, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Tübingen University, University of Copenhagen, University of Queensland, and Queensland University of Technology. Atrogi’s unique platform enables the synthesis of compounds capable of modulating signaling downstream of adrenergic receptors in novel ways. By measuring the specific activation of numerous downstream signaling events, Atrogi has created a proprietary library of compounds that engage discrete signaling pathways, each tailored to enhance beneficial effects while mitigating potential side effects in different therapeutic areas. Atrogi's iterative approach to drug development allows for the generation of compounds with optimized signaling profiles and improved efficacy. References (1) Paper: “The novel adrenergic agonist ATR-127 targets skeletal muscle and brown adipose tissue to tackle diabesity and steatohepatitis” Notes to Editors About Atrogi AB Atrogi is a clinical-stage biotech company developing first-in-class, insulin-independent treatments for type 2 diabetes (T2D) and related metabolic disorders, including obesity and muscle-wasting disorders. Atrogi’s lead compound, ATR-258 for T2D, completed a Phase 1a/b clinical trial in March 2024, with Phase II trials planned by the end of 2024. Atrogi also has compounds in pre-clinical development for the treatment of obesity and muscle wasting disorders. ATR-258 binds to the beta-2 adrenoreceptor, initiating a process that mediates the transportation of glucose into skeletal muscle, lowering blood glucose levels and positively affecting several organs affected by T2D. The proprietary small-molecule compound activates the receptor in a novel manner, causing selective modulation and a distinct signaling profile. Atrogi’s platform extends beyond the adrenergic receptor system, offering the potential for application to other GPCRs. By leveraging the signaling complexity of GPCRs, Atrogi aims to develop tailored compounds that engage specific pathways relevant to different clinical conditions, paving the way for safer, more effective therapies. The company has raised over EUR 24 m in total since inception from investors, including Flerie Invest, Korea Investment Partners (KIP) and private investors. This includes a SEK 90 million (approx. EUR 7.6 m) rights issue. The company has also been awarded non-dilutive grants of over EUR 1.5 million from international organizations such as Eurostars, as well as grants from SweLife in recognition of the company’s unique discovery of receptor signaling. The company is based in Solna, near Stockholm, Sweden. Follow the company on LinkedIn and visit its website. Media Contacts Atrogi Alexandra Ekman Ryding, CEO alexandra@atrogi.com Scius Communications (for Atrogi) Katja Stout katja@sciuscommunications.com Tel: +44 7789 435990 Daniel Gooch Tel: +44 7747 875479 daniel@sciuscommunications.com