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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.

BOSTON--( BUSINESS WIRE )--Please replace the release with the following corrected version due to revisions to the second and fourth bullet points in the body of release. The updated release reads: BPGbio Receives FDA Rare Pediatric Disease Designation for its Investigational Treatment for Epidermolysis Bullosa This marks the company’s second Rare Pediatric Disease Designation for BPM31510 franchise in the last two months BPM31510T targets mitochondrial machinery to promote wound healing in EB patients BPGbio, Inc ., a leading biology-first, AI-powered, clinical stage biopharma focused on mitochondrial biology and protein homeostasis , today announced that the U.S. Food and Drug Administration (FDA) has granted a Rare Pediatric Disease Designation for BPM31510T, its investigational treatment for epidermolysis bullosa (EB). This designation coincides with EB Awareness Week, observed annually from October 25-31, highlighting the urgent need for innovative EB treatments. EB, a rare genetic connective tissue disorder, affects roughly one in 20,000 children in the United States, leaving them with delicate skin prone to blistering, chronic wounds, scarring, and increased cancer risks. Severe cases of EB can result in life-threatening complications, including an aggressive form of squamous cell carcinoma (SCC). Currently, there is no cure and treatment options are limited. “The EB community is thrilled by this designation, as EB patients and families remain hopeful for more effective treatments,” said Brett Kopelan , Executive Director, DEBRA of America , the largest EB patient advocacy organization in the U.S. “We deeply appreciate BPGbio’s commitment to advancing research and expanding options for the EB community.” The FDA’s Rare Pediatric Disease Designation is intended for companies developing treatments for pediatric diseases that currently lack approved therapies. This designation provides BPGbio eligibility for a priority review voucher upon BPM31510T’s approval for EB. It is the second Rare Pediatric Disease Designation that BPGbio has received for BPM31510, with the initial designation awarded last month for primary CoQ10 deficiency . BPM31510T has also received the FDA’s Orphan Drug Designation. “EB is difficult to manage clinically and on a day-to-day basis due to fragile skin resulting in painful and persistent blistering wounds that can, in some subtypes, progress into squamous cell carcinoma, an aggressive form of skin cancer, which is the leading cause of mortality in the severe form of EB,” said Robert S. Kirsner, M.D., Ph.D. , Chairman and Harvey Blank Professor of Dermatology at the University of Miami Miller School of Medicine, and Vice President of the Wound Healing Society. “In its Phase I clinical trial, BPM31510T was well-tolerated and demonstrated potential efficacy as an easy-to-use, topical therapy for EB. This designation, and the continued clinical development for BPM31510T, offers new hope to patients suffering from EB and their families.” BPM31510T, developed to support wound healing in EB patients, targets cellular and mitochondrial processes that promote wound healing. By influencing key pathways involved in wound healing—including inflammation, cell proliferation, and tissue remodeling—BPM31510T has been shown to support wound care in EB across multiple subtypes. Following successful preclinical and Phase I studies, BPGbio is partnering with DEBRA of America to advance BPM31510T into Phase II/III trials, anticipated to begin in 2025. “Receiving a second Rare Pediatric Disease Designation for our BPM31510 franchise underscores the power of our NAi Interrogative Biology Platform,” said Niven R. Narain , Ph.D., President and CEO, BPGbio. “While conditions like EB, CoQ10 deficiency, and cancer, may seem unrelated, they share mitochondrial dysfunction as a root cause. BPGbio is committed to further developing BPM31510 in the mitochondria medicine space through strategic partnerships to bring the benefits of therapeutics to underserved patients.” BPM31510 is BPGbio’s leading clinical candidate in topical, intravenous, and oral formulations. BPM31510T has completed a phase 1 trial for EB and phase 2 for SCC; BPM31510IV is being studied in ongoing Phase 2B for glioblastoma multiforme (orphan drug) and has completed a Phase 2A for pancreatic cancer (orphan drug); BPM31510IV has recently received FDA Rare Pediatric Disease designation for its potential treatment for primary coenzyme Q10 deficiency . The company is planning a potential pivotal trial of BPM31510IV targeting multiple CoQ10 deficiency mutations at multiple U.S. and EU sites; BPM31510 Oral A Phase 2 trial for Sarcopenia is currently being planned for BPM 31510 Oral. “We are honored to offer hope for children who suffer from debilitating wounds and pain,” said Vijay Modur , M.D., Ph.D., Chief Medical Officer, BPGbio. “Preliminary evidence from Phase 1 clinical trial suggests BPGbio’s BPM31510 appears to be well-tolerated and potentially efficacious in improving wound healing. We’re looking forward to validating these results further through Phase II/III trials.” About BPM31510 BPM31510IV is BPGbio’s lead candidate in late-stage development for aggressive solid tumors such as glioblastoma multiforme (GBM) and pancreatic cancer . Other topical and oral formulations of the investigational agent are also being developed as a potential treatment for several rare diseases. The compound has demonstrated a tolerable safety profile and shown potential clinical benefits across multiple disease indications. Validated by BPGbio’s NAi Interrogative Biology platform , BPM31510 induces a hallmark shift in the tumor microenvironment (TME) by modulating mitochondrial oxidative phosphorylation in aggressive tumors, leading to cancer cell death. In many mitochondrial diseases, restoring CoQ 10 levels can overcome the effect of mutations in genes that lead to mitochondrial dysfunction. BPM31510 has been granted Orphan Drug Designation by the FDA for GBM, pancreatic cancer, and epidermolysis bullosa (EB), as well as Rare Pediatric Disease Designation for primary CoQ10 deficiency and EB. About BPGbio BPGbio is a leading biology-first AI-powered clinical stage biopharma focused on mitochondrial biology and protein homeostasis. The company has a deep pipeline of AI-developed therapeutics spanning oncology, rare disease and neurology, including several in late-stage clinical trials. BPGbio’s novel approach is underpinned by NAi , its proprietary Interrogative Biology Platform, protected by over 400 US and international patents; one of the world’s largest clinically annotated non-governmental biobanks with longitudinal samples; and exclusive access to the most powerful supercomputer in the world. With these tools, BPGbio is redefining how patient biology can be modeled using bespoke Bayesian AI specifically designed for solving large-scale biology challenges. Headquartered in greater Boston, the company is at the forefront of a new era in medicine, combining biology, multi-modal data, and AI to transform the way we understand, diagnose, and treat disease. For more information, visit www.bpgbio.com .

Primary CoQ10 deficiency is a rare mitochondrial disorder that impacts fewer than one in 100,000 individuals. Credit: StudioMolekuul via Shutterstock. BPGbio has received a Rare Pediatric Disease Designation from the US Food and Drug Administration (FDA) for BPM31510IV to treat primary coenzyme Q10 deficiency, an ultra-rare mitochondrial disorder. Primary CoQ10 deficiency affects fewer than one in 100,000 people. It hampers the body’s ability to produce CoQ10, a molecule crucial for cellular energy production and biomembrane stabilisation. The deficiency can lead to severe developmental delays, weakness of muscle, seizures, and potentially fatal organ damage, with symptoms often appearing in early childhood. Oral CoQ10 supplements failed to reach therapeutic levels in severely affected organs. BPGbio’s BPM31510IV has shown potential in addressing this gap, leveraging the company’s NAi Interrogative Biology platform, which combines patient biology with AI-driven analysis. See Also: Potential for peptides to replace antibodies in radiopharma, says WuXi AppTec exec BPGbio’s mitochondrial disorder drug gets paediatric disease status It is not only a lead candidate for solid tumours such as glioblastoma multiforme and pancreatic cancer but also shows promise for various rare diseases. BPGbio president and CEO Niven Narain said: “BPM31510 has been developed in topical, IV and oral formulations and is a prime example of the power of our biology-first approach to drug discovery and development, illustrating the powerful predictive capabilities of our NAi Interrogative Biology platform, and the benefit of validating AI-derived predictions through wet lab experiments and in vivo modelling. “By using hypothesis-free causal AI to analyse vast amounts of biological data, we were able to uncover and validate new potential applications BPM31510, including its potential to address mitochondrial diseases like primary CoQ10 deficiency.” BPGbio’s investigational treatment has also received orphan drug designation for glioblastoma multiforme, pancreatic cancer, and epidermolysis bullosa, in addition to the rare pediatric disease designation for primary CoQ10 deficiency.