LIPC

CAMBRIDGE, England--( BUSINESS WIRE )--Napp Pharmaceuticals Limited, a member of the international network of Mundipharma independent associated companies, today announced that the Medicines and Healthcare Products Regulatory Agency (MHRA) has authorised rezafungin for the treatment of invasive candidiasis in adults in Great Britain (GB). 1,2 The authorisation was based on positive results from the pivotal ReSTORE Phase III clinical trial which demonstrated statistical non-inferiority for rezafungin, dosed once weekly, when compared to the current standard of care, caspofungin, dosed once daily. 2,3,4 These findings are supported by the STRIVE Phase II clinical trial and an extensive nonclinical development program. 3,4 ReSTORE, a multicentre, prospective, randomised and double-blind Phase III trial compared the efficacy and safety of intravenous rezafungin with intravenous caspofungin in eligible patients with invasive candidiasis. 2,3 The primary efficacy outcome was global response (confirmed by the Data Review Committee [DRC]) at day 14. 3 Global response was determined from clinical response, mycological response, and radiologic response (for qualifying subjects with invasive candidiasis). 2,3 Of the 187 patients in the modified intention-to-treat (mITT) population, 59.1% of patients in the rezafungin group (55/93) and 60.6% of patients in the caspofungin group (57/94) had a global response of cure at day 14 (weighted treatment difference −1.1% [95% CI −14.9, 12.7]. 2,3 Non-inferiority was to be concluded if the lower bound of the 95% confidence internal (CI) for the difference in Day 14 cure rates (rezafungin – caspofungin) was >-20%. 2 Rezafungin was generally well tolerated in clinical trials, to date very common adverse reactions include hypokalaemia, pyrexia, and diarrhoea. Common adverse reactions include anaemia, hypomagnesaemia, hypophosphataemia, hypotension, wheezing, vomiting, nausea, abdominal pain, constipation, erythema, and rash. Increased blood alkaline phosphatase, hepatic enzymes, alanine aminotransferase, aspartate aminotransferase and blood bilirubin were also common. Uncommon adverse events were hyperphosphataemia, hyponatraemia, phototoxicity, tremor and increased eosinophil count. There were spontaneous reports of urticaria (frequency not known). Transient infusion-related reactions have occurred with rezafungin, characterised by flushing, sensation of warmth, nausea, and chest tightness. 2 Rezafungin may cause increased risk of phototoxicity. Eligible patients should be advised to avoid sun exposure and other sources of UV radiation without adequate protection during treatment and for 7 days after the last administration of rezafungin. 2 Invasive candidiasis , is a severe, life-threatening infection of the bloodstream and/or deep/visceral tissues. 10,11 It affects seriously ill people, especially those with a weakened immune system and the mortality rate can be 40% or more. 12,13 It can place a large burden on the healthcare system, with the potential for extended treatment regimens and long hospital stays. 14 In the last 15 years there have been no new treatments and morbidity and mortality rates remain largely the same, indicating the need for alternative treatment options. 5-9,15 Professor P. Lewis White PhD, FECMM, FRCPath, Consultant Clinical Scientist and Head of the PHW Mycology Reference Laboratory, Honorary Professor, Cardiff University Centre for Trials Research said “ Invasive candidiasis remains a difficult-to-treat disease which has a significant impact on critically ill and immunocompromised patients. With limited advances in treating this condition over the past 15 years, today’s announcement is a positive step towards supporting eligible patients and could enable the healthcare professional community an alternative way to manage these patients with invasive candidiasis using a new, once-weekly intravenous treatment option .” “ This authorisation is a culmination of years of developing an additional treatment option for eligible adult patients suffering from invasive candidiasis and underscores our commitment to supporting management of infectious diseases, ” said Dr Ben David, Medical Director for Northern Europe at Mundipharma. Rezafungin has been granted Orphan Drug Designation (ODD) in GB for the treatment of invasive candidiasis in adults. 1 The MHRA grants ODD to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 5 in 10,000 people in GB where no satisfactory method of diagnosis, prevention or treatment of the condition concerned exists, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition. 16 *ENDS* About invasive candidiasis Invasive candidiasis (IC) continues to be an area of significant unmet need, especially for critically ill patients in hospitals and patients with compromised immune systems. 14 Despite a number of available treatments, the mortality rate for patients with invasive candidiasis can be 40% or more. 13,14 IC is characterised as a severe, life-threatening systemic Candida infection of the bloodstream and/or deep/visceral tissues. 17 About Rezafungin Rezafungin is a novel once-weekly echinocandin that has been developed for the treatment of invasive candidiasis in adults. 18 About Napp Napp Pharmaceuticals Limited is part of Mundipharma, a global healthcare company with a presence across Africa, Asia Pacific, Canada, Europe, Latin America, and the Middle East. Mundipharma is dedicated to bringing innovative treatments to patients in the areas of pain management, infectious disease and consumer healthcare as well as other severe and debilitating disease areas. Our guiding principles, centered around Integrity and Patient-Centricity, are at the heart of everything we do. For more information visit www.mundipharma.com Future clinical trial data A second Phase III clinical trial of rezafungin for the prevention of invasive fungal disease in patients undergoing allogeneic blood and marrow transplantation (ReSPECT trial) is currently being conducted. 18 Registered office addresses NAPP PHARMACEUTICALS LIMITED a company having its registered office at Cambridge Science Park, Milton Road, Cambridge CB4 0AB, England. MUNDIPHARMA RESEARCH LIMITED, a company having its registered office at Cambridge Science Park, Milton Road, Cambridge, CB4 0AB, England. ® REZZAYO is a Registered Trademark of Cidara Therapeutics, Inc, used under license. References 1. UK Medicines and Healthcare Products Regulatory Agency authorisation. Available at: https://www.gov.uk/government/news/rezzayo-approved-to-treat-adult-patients-with-invasive-candidiasis (last accessed February 2024) 2. REZZAYO ® Summary of Product Characteristics. 3. Thompson GR, et al. Lancet 2023;401(10370):49–59. 4. Thompson GR, et al. Lancet Infect Dis 2023; https://doi.org/10.1016/S1473-3099(23)00551-0 5. Ham YY, et al. Future Microbiology 2021;16(1):27–36. 6. CANCIDAS (formerly Caspofungin MSD) EPAR. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/cancidas-previously-caspofungin-msd (last accessed February 2024). 7. Vfend (voriconazole) EPAR. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/vfend (last accessed February 2024). 8. Ecalta (anidulafungin) EPAR. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/ecalta (last accessed February 2024). 9. Mycamine (micafungin) EPAR. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/mycamine (last accessed February 2024). 10. Pappas PG, et al. Nat Rev Dis Primers 2018;4:18026. 11. CDC. Invasive candidiasis. Available at: https://www.cdc.gov/fungal/diseases/candidiasis/invasive/definition.html (last accessed February 2024). 12. Kullberg BJ, Arendrup MC. N Engl J Med 2015;373:1445–56. 13. Bassetti M, et al. Crit Care 2019;23(1):219. 14. Cortegiani A, et al. Cochrane Database Syst Rev 2016;2016:Cd004920. 15. Bassetti M, et al. J Antimicrob Chemother 2018; 73 Suppl 1: i14–i25 doi:10.1093/jac/dkx445. 16. UK Medicines and Healthcare Products Regulatory Agency, Guidance – Orphan medicinal products. Available at: https://www.gov.uk/guidance/orphan-medicinal-products-in-great-britain (last accessed February 2024). 17. Cortes JA, Corrales IF. Invasive candidiasis: Epidemiology and Risk Factors. November 2018. Available at https://www.intechopen.com/chapters/64365 (last accessed February 2024). 18. Cidara Therapeutics and Mundipharma Announce Positive Topline Results from the Global Phase 3 Pivotal ReSTORE Trial of Rezafungin for the Treatment of invasive candidiasis. Available at https://www.mundipharma.com/Cidara-Therapeutics-and-Mundipharma-Announce-Positive-Topline-Results-from-the-Global-Phase-3-Pivotal-ReSTORE-Trial-of-Rezafungin-for-the-Treatment-of-Candidemia-and-Invasive-Candidiasis (last accessed February 2024). Job code: UK-RZF-2300053 Date of preparation: February 2024

Triglyceride-rich LDL particles were found to be directly causal in ASCAD based on Aitia's Digital Twins built on G3's Global Multi-omic Clinical Study Data and Aitia's Causal AI Technology LDL-Triglycerides may become an important diagnostic biomarker in ASCAD and may lead to new therapeutics ATLANTA and SOMERVILLE, Mass., Jan. 12, 2023 /PRNewswire/ -- G3 Therapeutics, a life sciences company that leverages large-scale multi-omic biological big data to develop life-changing therapeutics and diagnostics, and Aitia, the leader in the application of Causal AI and "Digital Twins" to discover and develop new drugs, today announced results of research that identified new causes of ASCAD. The results are found in the paper "Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development', published in the journal Frontiers in Cardiovascular Medicine () The analysis conducted by G3 Therapeutics, Aitia, and their team of scientific collaborators discovered that triglyceride-rich LDL particles appeared directly upstream from ASCAD in the Digital Twin models, suggesting causality of triglyceride-rich LDL particles. The role of the triglyceride-rich LDL particles was independent of the cholesterol content of LDL particles (independent of LDL-C) and the potential causality was further confirmed by genetic validation, based on the hepatic lipase gene ("LIPC"). The analysis also revealed that atherogenic lipoproteins, inflammation, and endothelial dysfunction are involved in ASCAD, lending additional credence to the novel findings. These findings imply that LDL-TG could be a novel diagnostic marker for ASCAD and could also open up potential novel treatment targets for atherosclerosis, focusing on triglyceride-rich LDL particles. "For decades, we have singularly focused on LDL-cholesterol as the sole treatment target in atherosclerotic coronary artery disease. Now, this new discovery of triglyceride-rich LDL particles opens a previously untapped set of opportunities to bring novel diagnostic and therapeutic approaches to our patients suffering from devastating cardiovascular disease. Our discovery demonstrates the power of the combination of biological big data and causal AI in bringing entirely novel treatments to our patients.", said Szilard Voros, MD, CEO and founder of G3 Therapeutics. "This landmark result clearly demonstrates the power of causal AI and Digital Twins to reveal the hidden circuitry of cardiovascular disease from large-scale multi-omic data", said Colin Hill, CEO and co-founder of Aitia. "70 years of cardiovascular biology including LDL, PCSK9, and Lp(a) were reconstructed in a hypothesis-free fashion in a few months, which created the opportunity to rapidly discover new drivers of atherosclerotic disease such as triglyceride-rich LDL that has eluded researchers for decades. A new era of AI-driven techbio discovery has begun." About the G3LOBAL Database™ G3 Therapeutic's G3LOBAL Database™ is derived from the GLOBAL clinical study (NCT01738828), an international prospective, multi-center study recruiting up to 10,000 patients to characterize novel disease networks and biomarkers. GLOBAL is the largest and most comprehensive pan-omic study combining whole genome sequencing, whole genome methylation, whole transcriptome sequencing, unbiased proteomics, metabolomics, lipidomics, and lipoprotein proteomics with coronary computed tomographic (CT) angiography, an advanced imaging technology for phenotyping, which allows the precise classification of disease in patients. About G3 Therapeutics G3 Therapeutics is a global leader in the application of unbiased biological big data in transforming the drug discovery and drug development process. G3 Therapeutics has assembled a revelatory platform that utilizes deep phenotyping, deep molecular profiling and deep learning for the discovery, genetic validation, and development of novel drug targets. G3 Therapeutics' foundational biological big data platform has been built on the GLOBAL Clinical Study (NCT01738828), enrolling over 7,500 individuals from around the world. G3 Therapeutics' deep molecular profiling approach includes whole genome sequencing, as well as the measurement of all other relevant "omics" measurements including DNA methylation, RNA sequencing, proteomics, metabolomics, and lipidomics. G3 Therapeutics has already discovered and patented relevant biomarkers and is starting the development of several novel drugs based on its proprietary platform and discoveries. For additional information, please visit About Aitia Aitia is the leader in the application of Causal AI and Digital Twins to discover the next generation of breakthrough drugs. By leveraging the convergence of multi-omic patient data, high-performance computing, and causal learning and AI, Aitia is revealing the hidden biological mechanisms of disease to create Digital Twins of disease in oncology, neurodegenerative disorders, and immunology. Gemini Digital Twins are being used today to discover novel therapies and accelerate R&D in multiple myeloma, prostate cancer, Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease, with several more in development. Aitia's partners include seven of the top ten pharmaceutical companies, leading academic research and medical centers, medical societies, leading multi-omic data companies, and patient advocacy groups globally. For more information, please visit Follow us on social media: LinkedIn, Twitter Media Contacts: G3 Therapeutics Brad Brown Co-founder and COO [email protected] or Aitia Zena Sfeir Director of Marketing [email protected] SOURCE Aitia