Inflammatory pain

Dr. David J. Bearss, CEO, will present data from the Phase II study evaluating the efficacy of HT-6184 on post-procedural inflammatory and pain responses on Thursday, September 12, 2024 LEHI, Utah, Sept. 10, 2024 /PRNewswire/ -- Halia Therapeutics, Inc. (Halia), a clinical-stage biopharmaceutical company at the forefront of developing innovative treatments for inflammatory and neurodegenerative diseases, today announced that David J. Bearss, Ph.D., President and CEO of Halia Therapeutics, will present results from Halia's completed Phase II randomized, single-dose, placebo-controlled, double-blind, parallel-group clinical study (NCT06241742) evaluating the efficacy of HT-6184 in post-procedural inflammatory and pain responses at the upcoming 6th Inflammasome Therapeutics Summit taking place September 10-12, 2024, in Boston, MA. HT-6184 is a first-in-class, selective, and orally bioavailable inhibitor of the NEK7/NLRP3 inflammasome. Halia's investigational drug is designed to improve patients' lives by targeting chronic inflammatory disorders and neurodegenerative diseases. Presentation Details: Title: Leveraging Inflammatory-Induced Pain as an Innovative & Alternative Endpoint for a Time-Effective Measurement of Therapeutic Benefit Date: September 12, 2024 Time: 8 a.m. ET Presenter: David J. Bearss, Ph.D., President and Chief Executive Officer, Halia Therapeutics Session: From Biomarkers to Endpoint & Even Clinical Trial Design: Innovations in Clinical Development Strategies to Advance Inflammasome Therapeutics Dr. Bearss will also participate in the panel discussion: 'What are the Future Directions of the Inflammasome Therapeutics Landscape? A Glimpse into the Next 5 Years' which will take place on September 12 at 2:30 p.m. ET. The Inflammasome Therapeutics Summit is an annual event focused on advancing the development of inflammasome-targeting therapies. This summit gathers biopharma professionals and top academics in the field to offer exclusive clinical insights as well as to discuss the latest advancements in inflammasome research. To view the full agenda, please visit . About HT-6184 Clinical Trial to Reduce Inflammation and Pain The clinical trial (NCT06241742) is a Phase II randomized, single-dose, placebo-controlled, double-blind, parallel-group study designed to evaluate the ability of HT-6184 to attenuate diagnostic biomarkers of post-procedure acute inflammation and manage pain following third molar extraction. Subjects were given a single oral dose of HT-6184 or placebo before oral surgery to remove their third molar teeth and were monitored for safety and to rate their pain intensity and for biomarkers of post-procedure acute inflammation after surgery. The study was conducted at CenExcel JBR in Salt Lake City, Utah. About the Post Procedural Inflammatory Response Globally, over 300 million major surgical procedures are performed each year1. Many of these surgeries lead to inflammatory responses that complicate recovery and lead to acute pain and loss of productivity for patients recovering from the surgery. About NLRP3 NLRP3, an innate immune sensor, is activated in response to various pathogenic and sterile stimuli. Activation of NLRP3 triggers the release of the pro-inflammatory cytokines IL-1β and IL-18 and induces a lytic cell death process called pyroptosis. These processes lead to systemic chronic inflammation. Halia scientists and our collaborators have shown that HT-6184 inhibition of NLRP3 in preclinical models prevents the formation of the NLRP3 inflammasome and promotes its disassembly once formed, thereby inhibiting the production and release of IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome is thought to drive the onset and progression of many conditions, including fibrotic, dermatological, and auto-inflammatory diseases. Significant neurodegenerative and neuroinflammatory disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis are also driven by NLRP3 activation. About HT-6184 HT-6184 represents an innovative approach as it is the first drug candidate to target the protein NEK7 through an allosteric mechanism. NEK7 is an essential component of the NLRP3 inflammasome and is critical for its assembly and the maintenance of NLRP3 activity. In preclinical models, Halia has shown that inhibiting the ability of NEK7 to bind to NLRP3 leads to a disruption in the formation of the NLRP3 inflammasome complex, thereby inhibiting the signaling from the inflammasome and reducing the inflammatory response. Preclinical models also showed that in addition to disrupting the formation of the NLRP3 inflammasome, HT-6184 promotes the disassembly of the inflammasome once activated (Halia unpublished data). About Halia Therapeutics, Inc. Halia Therapeutics is discovering and developing a pipeline of novel therapeutics to improve patients' lives with chronic inflammatory disorders and neurodegenerative diseases, with its initial programs targeting NEK7 and LRRK2. Halia's lead candidate, HT-6184, a novel NEK7/NLRP3 inhibitor, has completed a Phase I study (NCT05447546) evaluating the safety and tolerability of HT-6184 when administered as single or multiple oral doses at escalating dose levels in healthy volunteer subjects and has also completed a Phase II trial evaluating the efficacy of HT-6184 on post-procedure diagnostic biomarkers of inflammation and pain (NCT06241742). Halia is currently undergoing a Phase II trial investigating the efficacy of HT-6184 for the treatment of lower-risk myelodysplastic syndromes (LR-MDS). The company's headquarters are in Lehi, Utah. For more information, visit or follow us on LinkedIn and Twitter (X). Company Contact Halia Therapeutics [email protected] +1 (385) 355-4315 Media Contact: Ignacio Guerrero-Ros, Ph.D. Russo Partners, LLC +1 (646) 942-5604 [email protected] References: Meara, John G., Andrew JM Leather, Lars Hagander, Blake C. Alkire, Nivaldo Alonso, Emmanuel A. Ameh, et al. Global Surgery 2030: evidence and solutions for achieving health, welfare, and economic development. The Lancet. 2015; 386: 569-624 SOURCE Halia Therapeutics

Menthol sensing appeared long before cold sensing, suggesting distinct activation modes that can be disentangled, paving the way for new pain therapies without adverse thermal side effects. Chronic pain affects millions worldwide, and current treatments often rely on opioids, which carry risks of addiction and overdose. Non-addictive alternatives could revolutionize pain management, and new research targeting the human protein which regulates cold sensations, brings scientists closer to developing pain medications that don't affect body temperature and don't carry the risks of addiction. Research published in Science Advances on June 21, led by Wade Van Horn, professor in Arizona State University's School of Molecular Sciences and Biodesign Center for Personalized Diagnostics, has uncovered new insights into the main human cold and menthol sensor TRPM8 (transient receptor potential melastatin 8). Using techniques from many fields like biochemistry and biophysics, their study revealed that it was a chemical sensor before it became a cold temperature sensor. "If we can start to understand how to decouple the chemical sensing of cold from actual cold sensing, in theory, we could make side-effect-free drugs," said Van Horn whose research focuses on membrane proteins involved in human health and disease. "By understanding the evolutionary history of TRPM8, we hope to contribute to designing better drugs that offer relief without the dangerous side effects associated with current painkillers." When a person touches a metal desk and it feels cold, the human body activates TRPM8. For cancer patients who are on certain kinds of chemotherapeutics, touching a desk can hurt. TRPM8 is also involved in many other types of pain as well, including chronic neuropathic and inflammatory pain. By further understanding this specificity of the chemical sensing of cold versus physically sensing cold, scientists can target relief without triggering the temperature regulation side effects often seen in TRPM8 clinical trials for pain treatments. In the research, the team used ancestral sequence reconstruction, a time machine for proteins of sorts, compiling the family tree of TRPM8 that exists today and then used that information to determine what the proteins from long-extinct animals might have looked like. Using computational methods to resurrect ancestral primate, mammalian, and vertebrate TRPM8, the researchers were able to understand how TRPM8 has changed over hundreds of millions of years by comparing the sequences of current proteins to predict the sequences of their ancient ancestors. Additionally, the combination of lab experiments and computational studies enable the researchers to identify critical places in TRPM8 that allow a more clear understanding of temperature sensing, which can be tested in subsequent experiments. "Comparative dynamics analysis of ancestral and human TRPM8 also supports the experimental data and will allow us to identify critical sites in temperature sensing, which we will be testing soon," said Banu Ozkan, professor in ASU's Department of Physics, who was involved in the study. The team then expressed these ancestral TRPM8s in human cells and characterized them using various cellular and electrophysiology techniques. "Ancestral protein-based studies allow us to focus on the lineage of most interest, such as human TRPM8, to alleviate concerns arising in drug discovery from speciation differences, like in mice and humans," said first author on the study Dustin Luu, an ASU School of Molecular Sciences doctoral alumnus, and current postdoctoral fellow in ASU's Biodesign Center for Personalized Diagnostics. Luu continued: "We discovered that surprisingly menthol sensing appeared way before cold sensing. The difference in appearance and attenuation of these activation modes suggest they are separate and can be disentangled with further research enabling new pain therapies without the adverse side effect in thermal sensing and thermal regulation, which has plagued TRPM8-targeted clinical trials." As science continues to uncover the mysteries of our biological mechanisms, studies like this exemplify how evolutionary biology and modern pharmacology can collaborate to address pressing medical needs and improve the quality of life for those suffering from chronic pain.

According to the latest statistics, cell and gene therapies are rapidly emerging as a hot topic in the pharmaceutical field due to their unique therapeutic advantages. A recent report has revealed the top 10 best-selling cell and gene therapy products globally in 2023. At the top of the sales ranking is Yescarta, Gilead's CAR-T cell therapy product, which leads the global CAR-T cell therapy market with sales of $1.498 billion, making it the overall sales champion in the cell and gene therapy field. Closely following are two products from Novartis, Zolgensma and Kymriah, which generated sales of $1.214 billion and $508 million, respectively, ranking second and third. In addition, several other products that made it to the TOP 10 also performed remarkably well, including Carvykti co-developed by Johnson & Johnson and Legend Biotech, Abecma co-launched by BMS and 2seventy bio, and Tecartus from Kite Pharma. It's worth mentioning that if the two antisense oligonucleotide (ASO) therapies for Duchenne muscular dystrophy, Exondys 51 and Amondys 45, developed by Sarepta Therapeutics, were included in the ranking, their 2023 sales of $540 million and $270 million, respectively, would also place them among the top ten. Looking at the sales ranking, CAR-T cell therapies occupy half of the market, fully demonstrating their outstanding position in the treatment of malignant hematological cancers. Meanwhile, gene therapies based on viral vectors, such as Zolgensma and Luxturna, have also shown impressive market performance. Looking forward, with the continuous emergence and launch of more innovative therapies, the cell and gene therapy field will embrace a broader development prospect and unlimited market potential. Menarini Group, as a leading pharmaceutical company in the Italian industry, has weathered 140 years of storms and emerged as an important force in the European and global pharmaceutical industry, thanks to its deep accumulation and excellent technology in the biopharmaceutical field. As a pharmaceutical giant with unique technology, products, and a huge R&D system, Menarini has always focused on the research and development of drugs for cardiovascular diseases, inflammatory pain, gastrointestinal diseases, oncology, and metabolic diseases. Headquartered in the historic city of Florence, the company has a team of over 17,700 excellent employees and operates in more than 140 countries around the world, with numerous subsidiaries, distributors, and franchisees. In recent years, Menarini has actively expanded its international business footprint and strengthened and expanded its position in the global market through a series of strategic acquisitions and collaborations. In the fields of oncology and infectious diseases, Menarini, with its rich product line and innovative technology, has provided many high-quality treatment options for patients worldwide. Take Tagraxofusp as an example, it is the first approved drug for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) and the first approved CD123-targeted drug, which has brought unprecedented hope for the clinical treatment of BPDCN patients. Overall, Menarini, with its 140-year deep accumulation and the spirit of continuous innovation, has achieved remarkable results in the fields of oncology and infectious diseases, and continues to provide patients with better treatment options. At the same time, the company also demonstrates strong competitiveness and broad development prospects in the international market.