Rheumatic Fever

SALT LAKE CITY--(BUSINESS WIRE)-- Foldax® Inc., a pioneer in the development of innovative, polymer heart valves, today announced a manufacturing agreement with Dolphin Life Science India LLP to enable in-country manufacturing of the TRIA™ polymer mitral surgical heart valve outside of the U.S. for the first time. The TRIA mitral valve is designed specifically to accommodate the anatomy and pressures of the mitral position. It combines the company’s proprietary polymer – LifePolymer™ – with an innovative valve design intended to resist calcification, withstand stresses and strains without failure, and restore patient quality of life without lifelong use of anticoagulants. The novel LifePolymer material and computer-designed valve help to democratize the manufacturing process, minimizing the people and processes associated with animal-based tissue valve manufacturing, enabling manufacturing in any location, and improving product variability, precision, repeatability, and quality. “Our collaboration with Dolphin Life Science India LLP represents a pivotal move toward expediting the commercial release of the TRIA valve in our first targeted commercial region of India,” said Ryan Stanfield, Vice President of Engineering and Operations with Foldax, Inc. “We are honored to collaborate with Foldax to bring the TRIA valve manufacturing capability to India, with the intent of making a positive difference in the lives of millions of rheumatic heart disease (RHD) patients who can benefit from this novel polymer valve,” said Mukesh Chovatiya, Managing Director of Dolphin Life Science India. Dr. Kaushal Pandey, an investigator in the Company’s recent India clinical trial of the TRIA valve, who believes it to be the fastest-enrolling clinical trial for any surgical mitral valve, commented, “We have a pressing need in India for alternatives to tissue and mechanical valves, as current commercial offerings often fall short in durability and patient acceptance. I am encouraged to see the Company’s progress in getting one step closer to making this exciting heart valve available to Indian patients who critically need it.” The TRIA heart valve and LifePolymer technology are considered investigational and are not available for commercial sale in the U.S. or any other region. Dolphin Life Science India LLP is an expert in manufacturing medical devices. The company is registered with India’s regulatory bodies, the Drugs Controller General of India (DCGI), and the Central Drugs Standard Control Organization (CDSCO). About Foldax Foldax Inc. is a medical device company committed to reinventing every aspect of the heart valve – from material to design to manufacturing – to develop surgical and transcatheter valves designed to last a lifetime addressing historical tradeoffs. To learn more about Foldax, visit Foldax investors include Angel Physicians Fund, Biostar Capital, Caltech, Glenview Capital, Kairos Ventures, Memorial Care Innovation Fund and Sayan Bioventures. View source version on businesswire.com: Contacts MEDIA CONTACT: Michelle McAdam, Chronic Communications, Inc. michelle@chronic-comm.com (310) 902-1274 Source: Foldax Inc. View this news release online at:

SALT LAKE CITY--(BUSINESS WIRE)-- Foldax®, Inc., a leader in the development of innovative, polymer heart valves, today announced completion of enrollment in the Indian clinical trial of the TRIA™ polymer surgical mitral heart valve. Positive 30-day data for the first 35 patients in the study was presented at the recent Transcatheter Cardiovascular Therapeutics (TCT) conference by Isaac George, M.D., Surgical Director of the Heart Valve Center at Columbia University. The data showed that TRIA valve implantation resulted in 0% reoperation, 0% blood clotting and 0% bleeding events. The TRIA mitral valve is designed specifically for the anatomy and pressures of the mitral position. It combines the company’s proprietary polymer – LifePolymer™ – with an innovative valve design intended to resist calcification, withstand stresses and strains without failure, and restore patient quality of life without lifelong use of anticoagulants. “We are excited to see early promising results from the TRIA polymer mitral valve,” said Kaushal Pandey, MD, with P.D. Hinduja Hospital in Mumbai, India. “The blood flow dynamics are excellent, and the polymer material properties are formulated to resist calcification, one of the main causes of tissue valve failure.” The Indian TRIA surgical mitral valve study is a prospective multicenter clinical trial. Since commencing in March 2023, the trial has enrolled its target of 66 patients across eight sites in India, making it one of the fastest-enrolling studies of any heart valve and reinforcing the need for a durable mitral valve replacement option. Patients will be assessed at six months and one year for safety, hemodynamic performance, and durability. Additionally, a registry tracking these patients for five years will be implemented. India was selected for the clinical trial because approximately two to three million people in the country have rheumatic heart valve disease caused by rheumatic fever, which attacks the mitral valve, and causes it to close improperly and leak. Patients often contract rheumatic disease early in life and their valves begin failing when they are still young. In the Indian TRIA mitral valve trial, the patient age ranges from 19 to 68 years old, with an average age of 39, much younger than the nearly 60-year-old average age for tissue valve replacement in other mitral studies. Sixty-two percent of patients are female, and 60 percent of female patients are less than 40 years old, significantly larger percentages than typically seen in clinical studies. “It is especially rewarding to offer the TRIA polymer heart valve to women of child-bearing age,” said Dasari Prasada Rao, M.D., Chief Cardiac Surgeon at Apollo Spectra Hospital in Ameerpret, Hyderabad. “The TRIA polymer valve is designed to last a patient’s lifetime, without the requirement of taking blood thinners indefinitely. With the TRIA valve, women can hold onto the hope of having children without facing repeat surgeries.” The lower average age and high percentage of child-bearing females suggests that both physicians and patients believe the TRIA valve with LifePolymer will not have the limited durability or quality-of-life tradeoffs seen with currently available heart valves. “Prior to TRIA, patients had to choose between tissue valves made from porcine or pericardial tissue that have limited durability and are not culturally acceptable in India, and mechanical valves that click audibly when opening and closing and require lifelong blood thinning medication,” said Anil Jain, M.D. with Epic Hospital in Gujarat. “With growing positive clinical experience, the TRIA valve has the potential to become the valve of choice for patients of all ages with mitral valve regurgitation.” “Treating the final patient in this rapidly enrolled Indian TRIA mitral surgical valve clinical study builds on the exciting phase of innovation and growth at Foldax over the past year,” said Gregory D. Casciaro, CEO of Foldax. “We now have patents in India covering both our LifePolymer material and our valve design, further acknowledging and protecting our innovative polymer and valves.” “Thanks to the expertise and support of our physician partners in both India and the United States, we can continue to clinically implant our ‘designed for mitral’ TRIA valves made with LifePolymer. Across our total clinical experience, over 150 valves have been implanted, making TRIA the most widely studied polymer valve in humans,” Casciaro continued. “We look forward to continuing to follow these patients and validating the robust nature of the TRIA valve.” The TRIA heart valve is for investigational use only and is not available for commercial sale. To learn more about Foldax, visit . About Foldax Headquartered in Salt Lake City, Utah, Foldax is reinventing every aspect of the heart valve – from material to design to manufacturing – to develop surgical and transcatheter valves designed to last a lifetime addressing historical tradeoffs, between tissue and mechanical valves. Foldax investors include Angel Physicians Fund, Biostar Capital, Caltech, Glenview Capital, Kairos Ventures, Memorial Care Innovation Fund and Sayan Bioventures.

Researchers have identified that a transient inflammatory pain causes mitochondrial and redox changes in sensory neurons that persist beyond pain resolution. These changes appear to predispose to a failure in resolution of pain caused by a subsequent inflammation. Additionally, targeting the cellular redox balance prevents and treats chronic inflammatory pain in rodents. Researchers from the Center for Translational Immunology at University Medical Center Utrecht (the Netherlands) have identified that a transient inflammatory pain causes mitochondrial and redox changes in sensory neurons that persist beyond pain resolution. These changes appear to predispose to a failure in resolution of pain caused by a subsequent inflammation. Additionally, targeting the cellular redox balance prevents and treats chronic inflammatory pain in rodents. Pain often persists in patients with an inflammatory disease, even after the inflammation has subsided. The molecular mechanisms leading to this failure in pain resolution and the transition from acute to chronic pain are poorly understood. For some time, there have been clues that mitochondrial dysfunction may be involved. In a clinical study, approximately 70 percent of patients with heritable mitochondrial diseases develop chronic pain. However, the exact role of mitochondria in the resolution of inflammatory pain is unclear. Mitochondrial disturbances To unravel the role of mitochondria in pain resolution, Hanneke Willemen PhD in the research group lead by Niels Eijkelkamp PhD (Center for Translational Immunology, UMC Utrecht) used a model of hyperalgesic priming. In this model, a transient inflammation causes neuronal plasticity, which results in persistence of pain after a subsequent inflammatory stimulus; a perfect model to study what goes wrong during pain resolution. Hanneke and co-workers identified that hyperalgesic priming in mice causes mitochondrial and metabolic disturbances in sensory neurons. The investigators associate these disturbances with an increase in the expression of a mitochondrial protein (ATPSc-KMT) which in a previous study has been linked to chronic pain in patients. By using genetic and pharmacological approaches they showed that inhibit mitochondrial respiration, ATPSCKMT expression and supplementation of one of the affected metabolites restores resolution of inflammatory pain and prevents chronic pain development. The results of this study- which was performed with several collaborators, including the University of Oslo (Norway) -- have been published this week in Cell Reports Medicine. Hanneke Willemen concludes: "In our study we provide evidence that a peripheral inflammation induces persistent mitochondrial and metabolic changes in sensory neurons, which affects the ability of neurons to resolve from hyperalgesia induced by a subsequent inflammatory trigger. Thus, metabolic changes in sensory neurons result in failure of endogenous pain resolution pathways and drive the transition to chronic pain. Importantly, targeting mitochondrial respiration, scavenging reactive oxygen species or supplementation with nicotinamide riboside (vitamin B3) both represent potential therapeutic strategies to restore failing pain resolution pathways, thereby treating chronic inflammatory pain." Transition to chronic pain Chronic pain is a leading cause of years lived in disability and impaired quality of life, yet treatment options are limited and often induce severe side effects. The current dogma is that pain resolution is the consequence of the dissipation of the drivers that induced the pain. However, in 12-30 percent of rheumatic arthritis patients pain persists while they have minimal joint inflammation or even are in remission. Accumulating evidence indicates that pain resolution after tissue damage or inflammation is not passive, but rather an active process that involves endogenous pain resolution mechanisms. Failing pain resolution pathways may lead to the transition from acute to chronic pain. Although the molecular mechanisms that contribute to failure in pain resolution are still poorly understood and need unraveling, this study fills a part of this void and identifies a potential therapeutic approach to promote pain resolution.