Ornithine Phenylacetate

Improved disease staging tool for hepatic encephalopathy, approved for use by FDA in phase 3 trials of IV ammonia scavenger (YAQ006)Dose-response data of oral ammonia scavenger (YAQ007) for prevention of HE recurrenceIn vivo demonstration of ammonia scavenger mechanism of action highlights potential synergistic combination with TLR-4 antagonist (YAQ005) LONDON, May 07, 2025 (GLOBE NEWSWIRE) -- Yaqrit, a late clinical-stage company developing life-saving treatments for advanced liver diseases, is this week revealing data on the progress of both its phase 3 and phase 2b/3 candidate drugs – YAQ006 (IV) and YAQ007 (oral) - for hepatic encephalopathy (HE) at the forthcoming European Association for the Study of the Liver (EASL) Congress, Amsterdam May 7-10th in advance of its clinical trials. Collectively, the data provide an enhanced understanding of the mechanism of action, determine treatment-initiation and endpoints within the HE patient population and define the dosage of YAQ007 (the oral formulation of the ammonia scavenger) to be used for the prevention of recurrence of overt HE. “EASL 2025 represents a great opportunity for Yaqrit to share data with clinicians and researchers in the liver disease community as we approach late-stage clinical investigation of YAQ006 and YAQ007,” said Troels Jordansen, Yaqrit’s Chief Executive Officer. “There are clear unmet medical needs in advanced liver disease: the EASL presentations demonstrate that Yaqrit is on course to put the right drug in the right patients at the right time and at the right dosage.” YAQ006 and YAQ007 are, respectively, the intravenous and oral formulations of L-ornithine phenylacetate (L-OPA), a potent ammonia-scavenging agent. Yaqrit is preparing to start a phase 3 trial with YAQ006 for hospital treatment of overt HE, a life-threatening complication of decompensated cirrhosis and a phase 2b/3 trial with YAQ007 for outpatient use to prevent recurrence of overt HE. One key disclosure at EASL is the development of a patient-staging protocol – mHEST (modified Hepatic Encephalopathy Staging Tool). Use of mHEST has been approved by the US Food and Drug Administration (FDA) to evaluate the primary endpoint of ‘clinically meaningful improvement’ for the phase 3 trial of YAQ006 in patients with overt HE. The strong levels of inter- and intra-rater concordance within mHEST will reduce dependence on subjective assessment and interpretation, helping clinical investigators at various centers make consistent choices in patient selection and endpoint attainment across the trial. Development and validation of the modified hepatic encephalopathy staging tool (mHEST) for grading of hepatic encephalopathy for accurate assessment and regulated clinical trials (SAT-210). Prof. Rajiv Jalan, Saturday 10th May. The dose-setting clinical study for YAQ007 (oral formulation of L-OPA) is described in a second EASL presentation. Patients who received 4 g of YAQ007 twice daily showed a decrease in plasma ammonia that was 6 times the decrease seen with rifaximin (550mg twice daily), an antibiotic used in the current standard treatment for hepatic encephalopathy. There was no significant difference in adverse events. Randomized, open-label, phase 2a comparator study to assess the pharmacodynamics, safety and pharmacokinetics of oral administration of mnk6106 (l-ornithine phenylacetate) vs. rifaximin in subjects with hepatic cirrhosis and a previous history of hepatic encephalopathy (SAT-209). Prof. Rajiv Jalan, Saturday 10th May. Transcription and metabolic analysis in mouse models of HE provides evidence that the mode of action of L-OPA may be complementary to that of YAQ005, a TLR4 antagonist, in treating hyperammonemia. This raises the possibility of improved therapeutic strategies in the future. Transcriptomic and metabolic insights into hyperammonemia: the complementary therapeutic roles of toll-like receptor 4 inhibitor and ornithine phenylacetate (THU-182). Dr. Supachaya Sriphoosanaphan, Thursday 8th May. “In treating and preventing advanced liver disease with multiple complicating factors in play, there is no substitute for understanding, whether in controlling clinical trial variables or understanding mechanisms of drug action,” said Professor Rajiv Jalan, Yaqrit’s Founder and Chief Medical Officer. “These impressive data underpin confidence in the clinical pathway for Yaqrit’s pipeline assets.” Information on Yaqrit’s eight presentations at EASL 2025 can be found on Yaqrit’s website under latest news. The full abstracts will be available on the EASL Congress website from 08:30AM CEST on 7th May 2025. Contact Company Troels Jordansen Email: Troels@Yaqrit.com Tel: +31 6 1834 5326 Contact Investors Mary-Ann Chang Email: Mary-Ann@Yaqrit.com Tel: +44 7483 284 853 About Yaqrit Yaqrit is a clinical-stage company discovering and developing innovative treatments for patients with advanced liver disease at high risk of hospitalization and death. Yaqrit’s pipeline includes three novel therapeutics at phase 2-3 of development and two medical devices providing acute and chronic treatments for advanced cirrhosis and acute-on-chronic liver failure where there is an urgent need for more effective treatments. More information is available at www.Yaqrit.com About Hepatic Encephalopathy Hepatic encephalopathy (HE) is a potentially reversible neurological dysfunction associated with excess ammonia in the blood. As many as 40% of decompensated cirrhosis patients are at risk of developing hepatic encephalopathy, with over 80,000 patients hospitalized in the US every year with overt episodes. The recurrence of hepatic encephalopathy is high: a second episode will follow the initial overt event within a year in 40-50% of patients.

Acute and chronic treatment for hepatic encephalopathy acquired from Mallinckrodt Pharmaceuticals in September 2024 Extended pre-clinical, clinical and IP package includes FDA and EMA orphan drug and FDA fast track designations IV formulation to enter phase 3 in 2025; oral formulation to enter phase 2b trials for HE prevention and phase 2a for urea cycle disorders Feb. 11, 2025 -- Yaqrit, a late clinical-stage company developing life-saving treatments for advanced liver disease, announced today that its recently acquired ammonia scavenger, L-ornithine phenylacetate (OPA), is progressing to phase 3 for treatment of acute hepatic encephalopathy, a life-threatening complication of decompensated cirrhosis. Development will be via Yaqrit’s newly formed subsidiary Amalive Limited, named to reflect the profound impact of ammonia levels in the lives of patients with advanced liver disease. Amalive is preparing an IV formulation for the phase 3, adapting the trial design based on clinical experience and using AI modelling to guide patient selection. In parallel, Amalive will progress an oral formulation into phase 2b trials for outpatient use in the prevention of HE recurrence. Amalive is also developing an oral liquid formulation to treat and prevent hyperammonaemia associated with urea cycle enzyme disorders, a rare genetic disease that affects children. “OPA is a key asset for Yaqrit, a potentially great molecule both clinically and commercially, and the creation of subsidiary dedicated to its development will ensure its full potential is realized,” said Troels Jordansen, Chief Executive Officer of Yaqrit. “For Yaqrit, this also opens the opportunity for further therapeutic and commercial collaborations. With the right partner, we are ready to advance this important treatment into phase 3, building on the accelerated lowering of blood-ammonia already demonstrated in life-threatening HE.” Yaqrit acquired full global rights, including development and commercial, for OPA in any indication from Mallinckrodt Pharmaceuticals in the second half of 2024. Mallinckrodt Pharmaceuticals will receive payments upon the achievement of certain late-stage milestones, plus royalties on sales. “OPA consolidates Yaqrit’s leading position in the development of novel therapies for liver disease,” said Professor Rajiv Jalan, Founder and Chief Medical Officer of Yaqrit. “OPA addresses ammonia toxicity, a frequent, high-mortality event in vulnerable, advanced liver disease patients. Not only can OPA directly impact the prospects of millions of patients with late-stage liver disease, but it also opens a window for additional interventions in this severely underserved population.” OPA was discovered at the Liver Failure Group, University College London, by Professor Rajiv Jalan, Yaqrit’s founder. Earlier development of OPA, including phase 2a and phase 2b studies of both IV and oral forms was undertaken at Ocera Therapeutics, a subsidiary of Mallinckrodt Pharmaceuticals. The available clinical data indicated that OPA reduces levels of toxic ammonia more rapidly than standard of care, facilitating resolution of hepatic encephalopathy, which is one of the most prevalent complications of advanced liver disease1. By removing neurotoxic levels of ammonia from the blood, OPA has the potential to rapidly lower the risk of mortality and multi-organ-failure. Yaqrit is a clinical-stage company discovering and developing innovative treatments for patients with advanced liver disease at high risk of hospitalization and death. Yaqrit’s pipeline includes three novel therapeutics at phase 2-3 of development and two medical devices providing acute and chronic treatments for advanced cirrhosis and acute-on-chronic liver failure where there is an urgent need for more effective treatments. More information is available at www.Yaqrit.com In over 10 million patients worldwide per year, liver cirrhosis progresses from an asymptomatic (compensated) form to the decompensated form at which point the liver can no longer undertake its usual functions. This leads to complications such as jaundice, infections, encephalopathy, ascites and bleeding. The most severe form of decompensation is the occurrence of multiorgan failure, a condition referred to as acute-on-chronic liver failure. These complications lead to increased morbidity with median survival falling from more than 12 years for compensated cirrhosis to about two years for decompensated cirrhosis and less than 3-months for those with multiorgan failure. Hepatic encephalopathy (HE) is a potentially reversible neurological dysfunction associated with excess ammonia in the blood. As many as 40% of decompensated cirrhosis patients are at risk of developing hepatic encephalopathy, with approximately 200,000 patients hospitalized in the US every year with acute episodes. The recurrence of hepatic encephalopathy is high: a second episode will follow the initial acute event within a year in 40-50% of patients. 1 OCR002-HE209 Phase 2b Efficacy/Safety of Ornithine Phenylacetate in Hospitalized Cirrhotic Patients with Hepatic Encephalopathy The content above comes from the network. if any infringement, please contact us to modify.