Nav1.8

Vertex Pharmaceuticals’ breakthrough in cystic fibrosis was a medicine that treats just 4% of patients who have the lung disorder. Today, Vertex’s portfolio of blockbuster CF products spans multiple drugs and drug combinations that can treat 90% of CF patients. CEO Reshma Kewalramani says Vertex aims to eventually reach all CF patients. But as the company moves closer to this goal, it brings up another part of the company’s strategy: pipeline diversification. The lion’s share of Vertex’s revenue comes from its CF portfolio, so revenue growth will have to come from adding on new therapeutic areas. Kewalramani sees this effort as building on the company’s CF work. “The real drive for Vertex is to invest in serial innovation, not just do it once, but do it repeatedly,” Kewalramani said, speaking in a fireside chat Monday at the World Medical Innovation Forum in Boston. “The goal here is to learn from all the lessons we have from CF and to invest in other disease areas.” presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum While Vertex is known for CF drugs, its research in pain medicines actually began even earlier. Vertex began its CF work about 20 years ago, Kewalramani said. The pain program started 25 years ago. The same scientists who worked on CF are the exact ones who now work on the pain program, she said. The past two decades have not seen new medications for acute pain or chronic pain. With innovation lacking in this therapeutic area, opioids filed the gap. Vertex is trying to change pain treatment paradigm with a different approach. Opioids treat pain by working in the central nervous system (CNS) to alter the perception of pain, Kewalramani said. By developing drugs that act on the peripheral nervous system, Vertex aims to avoid the safety, tolerability, and addictive problems of drugs that act on the CNS. Vertex’s most advanced pain product candidate is Suzetrigine, formerly known as VX-458. This non-opioid drug is a small molecule that stops pain signals from reaching the brain by blocking NaV1.8, a sodium channel in peripheral nerves. Kewalramani acknowledges that other companies are also developing sodium channel-blocking drugs. But Vertex is in position to bring one to patients sooner. The FDA accepted Vertex’s new drug application for Suzetrigine in July, setting a Jan. 30, 2025 target date for a regulatory decision. Vertex separates the pain market into three segments: acute, neuropathic, and musculoskeletal. The latter two segments are what many people would call chronic pain, Kewalramani said. Vertex is aims to discover, develop, and commercialize drugs for acute and neuropathic pain. These medicines may also work on musculoskeletal pain, but Kewalramani said that if the company enters the market for such drugs, it will be through a partnership. Sponsored Post What Healthcare Can Learn from Costco The path forward is clear: employers must evaluate their health plan the same way they do their Saturday shopping excursion. By Jeff Bak, Imagine360 CEO and President When Vertex launched 35 years ago, the company’s focus was developing small molecule drugs. With that in mind, Kewalramani said it’s interesting to note that Vertex is now the first to bring patients a CRISPR-Cas9 therapy, Casgevy. This genetic medicine won FDA approval last winter for treating the rare blood disorders sickle cell disease and beta thalassemia. Vertex’s broadening scope includes cell therapies for type 1 diabetes. VX-880 is what Kewalramani describes as a “naked cell” program. This therapy involves taking stem cells and coaxing them into differentiating into pancreatic islet cells that are sense glucose levels and release insulin. But this therapy requires chronic immunosuppression to prevent the immune system from destroying these cells. The next Vertex type 1 diabetes cell therapy, VX-264, takes these same cells and encapsulates them in a proprietary device that shields them from the immune system so no immunosuppression is needed. Both programs are in the clinic. The third program type 1 diabetes program is still preclinical, but here, Vertex is using CRISPR technology to edit cells to avoid sparking an immune response, obviating the need for immunosuppressants. Kewalramani said the potential to move from chronic therapies to a potentially curative therapy makes this one of the programs she is most excited about. Rather than focusing on specific technologies, Vertex is a disease-first company, she said. “We use whatever modality is needed to transform if not cure those diseases of interest,” Kewalramani explained. “One of the advantages to having that approach is that we can combine modalities.”

Positive Phase 1 results for LTG-001, Latigo's potential best-in-class non-opioid Nav1.8 inhibitor, demonstrated it to be well tolerated with rapid absorption Dr. Singla brings world-class expertise in analgesics, pain management, and clinical development to accelerate Company's pipeline of non-opioid pain medicinesOpioid addiction is a national public health concern – 3.75 million Americans go on to long-term chronic opioid use after low-risk surgery as up to 19% of patients exposed to opioids develop dependency THOUSAND OAKS, Calif., Aug. 19, 2024 /PRNewswire/ -- Latigo Biotherapeutics Inc. ("Latigo") today announced positive Phase 1 results for LTG-001, its lead potential best-in-class non-opioid pain medicine candidate. In a Phase 1 first-in-human clinical trial, data showed that LTG-001 was well tolerated with rapid absorption. LTG-001 is an oral, selective Nav1.8 inhibitor in development to treat acute and chronic pain at its source. The Company also announced the appointment of world-renowned analgesic scientist Neil Singla, M.D., as chief medical officer. Continue Reading Neil Singla, MD, Latigo Biotherapeutics Chief Medical Officer "Opioid addiction is a national public health concern and Latigo Bio is dedicated to being part of the solution. Latigo intends to develop non-opioid drugs that have meaningful efficacy, rapid onset of action, and superior safety to standard of care with no central nervous system effects, thereby reducing the risk of addiction," said Nima Farzan, Latigo's chief executive officer. "These positive Phase 1 results of LTG-001 in healthy volunteers are encouraging and give us tremendous confidence we are moving in the right direction. We look forward to continuing to progress the clinical program for LTG-001 along with our robust pipeline so that we can provide alternatives for patients that reduce dependency and offer effective pain relief." LTG-001 Phase 1 Clinical Trial Results Results from the Phase 1 clinical trial in 72 healthy subjects showed that LTG-001 was well tolerated and demonstrated rapid absorption with a Tmax of about 1.5 hours and predictable pharmacokinetics. Exposure was proportional across the dose range. Rapid onset of pain relief is critical for both acute and chronic pain management and achieving a Tmax in under two hours in this study indicates this may be possible. Additionally, no food effect was shown in the studied doses. Latigo's Phase 1 first-in-human clinical trial was designed to evaluate the safety and tolerability of single- and multiple-ascending oral doses, relative bioavailability, and food effect of LTG-001 versus placebo in healthy subjects. World-leading Analgesic Scientist Neil Singla, M.D., Appointed as Chief Medical Officer Latigo also announced the appointment of world-renowned analgesic scientist Neil Singla, M.D., as chief medical officer. Dr. Singla is the founder and past chief executive officer of Lotus Clinical Research, a world-renowned analgesic site and Clinical Research Organization combination. An expert in analgesic protocol design and implementation with a deep focus on minimizing variability in clinical trials with subjective endpoints, Dr. Singla has been instrumental in pioneering methodologies that enhance the rigor and outcomes of pain management studies. "Dr. Singla's extensive experience in analgesic protocol design and implementation will be invaluable as we work to address opioid addiction – one of the most critical public health issues of our time," said Mr. Farzan. "We look forward to Neil's leadership in advancing our pipeline of non-opioid pain medicines." "Latigo's innovative approach to pain management can play a significant role in providing effective non-opioid therapies to patients," said Dr. Singla. "Latigo's mission aligns with my passion for advancing treatments for pain management, without the risk of dependency. I am honored to have the opportunity to work with the Latigo team to deliver these life-changing non-opioid alternatives to people who desperately need them." Dr. Singla's innovative approach includes the development of novel patient education techniques that reduce placebo responses and increase effect sizes, significantly improving the quality of clinical trials in pain management. His work developing the abdominoplasty model for acute postoperative pain studies has set a new standard in the field, becoming a cornerstone for numerous new drug approvals. As a respected figure in the scientific community, Dr. Singla chairs the Clinical Trials Special Interest Group for the International Association for the Study of Pain (IASP) and has organized and chaired prominent scientific symposia on analgesic trials for both the IASP and the American Pain Society. He earned his medical degree from Northeast Ohio Medical University. About Opioid Use Disorder The opioid crisis remains one of the most critical public health issues of our time, with opioid addiction, also known as opioid use disorder, posing a significant threat to millions. According to the American Medical Association, 3% to 19% of individuals in the U.S. exposed to opioids develop chronic dependency. The National Institute on Drug Abuse reports that more than 80% of individuals who use illicit opioids, particularly heroin, began with prescription opioids. Each year, in the U.S. approximately 10,000 people die from overdoses involving prescribed opioids, and this number increases to 75,000 when including deaths from illicit opioids. In the U.S. alone, 143 million opioid prescriptions were written in 2020, and more than 10 million people misused opioids in 2019. Additionally, 3.75 million patients transition to long-term chronic opioid use after low-risk surgeries annually. The risks associated with prescription opioids are multifaceted, encompassing accidental overdoses, the presence of unused opioids in homes, and the progression from dependency to the use of dangerous illicit drugs like heroin and fentanyl. These alarming statistics underscore the urgent need for effective, rapid-acting non-opioid pain therapeutics that provide safer pain management alternatives and mitigate the opioid epidemic. About Latigo Biotherapeutics Latigo Biotherapeutics is a private clinical-stage biotechnology company developing innovative non-opioid pain medicines with potential best-in-class profiles that directly target the source of pain. Latigo's goal is to provide effective, rapid-acting pain relief without the risk of addiction. Latigo is supported by leading investors including Westlake Village BioPartners, 5AM Ventures, Foresite Capital, and Corner Ventures. For more information, please visit or follow us on LinkedIn. SOURCE Latigo Biotherapeutics

Vertex Pharmaceuticals, known for its outstanding contributions to the treatment of rare diseases, has recently made significant breakthroughs in new medical fields. The enterprise innovative drug trikafta success, set up in the leading position in the orphan drug research and development, annual sales is about to break through the billions of dollars in milestone. Now, Vertex has made a renewed push, announcing that the U.S. Food and Drug Administration (FDA) has accepted its Nav1.8 inhibitor VX-548 (Suzetrigine) for marketing and priority review for the treatment of moderate-to-severe acute pain, a major innovation in the analgesic field. VX - 548 research and development based on the deep understanding of sodium channel. These channels play a crucial role on the surface of the cell membrane, influencing neural pathways by regulating ionic potential changes. Among them, NaV1.8 subgene is specifically expressed in peripheral sensory neurons, which becomes an ideal target for pain treatment. Unlike traditional opioids, VX - 548 non addictive properties make it has significant advantage in pain management, to avoid the long-term use of opioid drugs may lead to dependence and a series of side effects. In phase III clinical trials, the curative effect of VX - 548 got strong authentication. The results of the trial showed that VX-548 was significantly superior to placebo in terms of pain relief, and although the difference was not significant when compared with opioids, its non-addictive nature undoubtedly opened up new possibilities for the treatment of acute pain. This finding suggests that VX-548 may become one of the standard treatments for pain management in the future, providing patients with a safer and more effective treatment option, while reducing the dependence on traditional opioids. Vertex pharmaceuticals of this innovation, not only shows its strong strength in the field of drug development, also brought a new dawn for global pain management field. With the further evaluation and possible launch of VX-548, we expect it to truly disrupt the existing analgesic market landscape and bring good news to hundreds of millions of pain patients around the world.