GPX4

The nomination of novel Kv1.3 inhibitor DPT0218 for the treatment of various immunological diseases including IBD and AD. • DPT0218 is a gut-restricted, highly potent and selective Kv1.3 inhibitor with excellent in vivo efficacy and safety profile in preclinical studies. This project further validates the capabilities of DP Technology's drug design platform RiDYMO ® . BEIJING, Jan. 30, 2024 /PRNewswire/ -- DP Technology, an " AI for Science" new paradigm-driven company, today announced the nomination of DPT0218, a novel small molecule targeting Kv1.3, as a preclinical candidate compound for the treatment of various autoimmune diseases, including Inflammatory Bowel Disease (IBD) and Atopic Dermatitis (AD). Continue Reading The voltage-gated potassium channel Kv1.3 is known to be crucial for maintaining the membrane potential required for the induction of inflammatory responses[1] because Kv1.3 inhibition reduces calcineurin mediated immune cell activation and proliferation[2]. Inhibition of Kv1.3 therefore offers a potential opportunity to specifically impair inflammatory immune cell activity and proliferation, including in antigen-activated T cells. Previously, Eli Lilly and Company (Lilly) made an initial payment of $60 million to D. E. Shaw Research (DESRES), with potential development and commercial milestone payments of up to $475 million for DES-7114, a lead compound of the Kv1.3-targeted therapeutics program. Recently, the activity of T cells has become a compelling intervention point in IBD[3]. Long-lived memory T-cell populations, particularly tissue resident subsets, may contribute to the chronicity of IBD and represent a potential target for therapy[4]. Kv1.3 expression was elevated in PBMCs from UC patients and correlated with the prevalence of Th1 and Th2 T cells. Kv1.3 expression was also detected on T cells from biopsies of UC patients[5]. It is estimated that there are at least 8 million IBD patients worldwide, of which more than 5 million in Europe and the U.S. The global market for autoimmune drugs is projected to reach $140 billion by 2028, with IBD medications accounting for $28 billion, representing 20% of the market share. DPT0218 is a potential 'best-in-class' highly selective Kv1.3 inhibitor with a novel scaffold. It has shown positive results in preclinical animal models of various autoimmune diseases such as IBD and AD. The compound exhibits sub-nanomolar potency and has achieved over 2000-fold selectivity for the Kv1.3 channel over a range of other ion channels, including Na + , K + , and Ca 2+ . It also showed unique DMPK profiles, high colon/ileum concentrations with low systemic exposure in multiple species, demonstrating an excellent safety profile in preclinical studies. "Although antibodies play a pivotal role in the treatment of moderate to severe IBD, their applications are limited by constrained therapeutic efficacy, immunogenicity, parenteral route of drug delivery, poor tolerability, and high cost." said Xiaomin Zhang, Head of Drug Discovery at DP Technology. "As a small molecule, DPT0218 has shown potent inhibition of T cell activation, proliferation, and cytokine secretion in both in vivo and in vitro studies, demonstrating its potential as an effective treatment for IBD. We'll actively advance DPT0218 to clinical research and explore its application to other autoimmune diseases." "DP Technology is the pioneer of AI for Science paradigm, dedicated to integrating 'AI + Simulation + Experiments' to address unmet clinical needs." said Weijie Sun, Founder and CEO of DP Technology. "The dynamics of ion channels are extremely complicated, and our RiDYMO® platform is unequivocally well-suited for the drug development of these highly challenging systems. The successful discovery of DPT0218 is an important step towards achieving the AI for Science vision. We look forward to collaborations with seasoned partners to advance this program to the next milestone." The RiDYMO® drug design platform integrates various AI and physical algorithms, dedicated to the development of drugs for "undruggable" targets and "best-in-class" molecules. As one of its core algorithms, Reinforced Dynamics (RiD) has a significant advantage in the sampling efficiency of molecular dynamics simulation. By fully leveraging the high-dimensional representation capabilities of neural networks, RiD can efficiently capture dynamic conformational changes in complicated biomolecular systems. The RiDYMO® platform is dedicated to studying the dynamics of biological systems and revealing cryptic binding sites, encompassing a range of challenging systems including protein-protein interactions (PPIs), intrinsically disordered proteins (IDPs), membrane proteins, RNA, and others. It has also been validated on "undruggable" targets including c-Myc and GPX4. About DP Technology DP Technology, an "AI for Science" new paradigm-driven company, dedicated to applying Artificial Intelligence and Molecular Simulation algorithms to solve important scientific problems by combining advanced computational methods.Relying on DP Technology's world-leading Dynamics-based drug design platform, RiDYMO®, and the de novo design platform for macromolecules, the team has established external collaborations and built up strong internal pipeline, focusing on three areas of CNS, oncology and autoimmune diseases. More： Business：[email protected] Media：[email protected] Reference SOURCE DP Technology

Researchers have demonstrated a new way of linking personal records and protecting privacy. The first application is in identifying cases of rare genetic disorders. There are many other potential applications across society. Macquarie University researchers have demonstrated a new way of linking personal records and protecting privacy. The first application is in identifying cases of rare genetic disorders. There are many other potential applications across society. The research will be presented at the 18th ACM ASIA Conference on Computer and Communications Security in Melbourne on 12 July. A five-year-old boy in the US has a mutation in a gene called GPX4, which he shares with just 10 other children in the world. The condition causes skeletal and central nervous system abnormalities. There are likely to be other children with the disorder recorded in hundreds of health and diagnostic databases worldwide, but we do not know of them, because their privacy is guarded for legal and commercial reasons. But what if records linked to the condition could be found and counted while still preserving privacy? Researchers from the Macquarie University Cyber Security Hub have developed a technique to achieve exactly that. The team includes Dr Dinusha Vatsalan and Professor Dali Kaafar of the University's School of Computing and the boy's father, software engineer Mr Sanath Kumar Ramesh, who is CEO of the OpenTreatments Foundation in Seattle, Washington. "I am very excited about this work," says Mr Ramesh, whose foundation initiated and supported the project. "Knowing how many people have a condition underpins economic assumptions. If a condition was previously thought to have 15 patients and now we know, having pulled in data from diagnostic testing companies, that there are 100 patients, that increases market-size hugely. "It would have a significant economic impact. The valuation of a company working on the condition would go up. Product costing would go down. How insurance companies account for medical costs would change. Diagnostic companies would target [the condition] more. And you can start to do epidemiology more precisely." Linking and counting data records might seem simple but, in reality, it involves many issues, says Professor Kaafar. First, because we are dealing with a rare disease, there is no centralised database, and the records are sprinkled across the world. "In this case in hundreds of databases," he says. "And from a business perspective, data is precious, and the companies holding it are not necessarily interested in sharing." Then, there are technical issues of matching data that is recorded, encoded, and stored in different ways, and accounting for individuals who are double-counted in and between different databases. And, on top of all that, are the privacy considerations. "We are dealing with very, very sensitive health data," Professor Kaafar says. This personal data isn't needed for a simple estimate of the number of patients and for epidemiological purposes. But, until now, it was needed to ensure that records are unique and can be linked. Dr Vatsalan and her colleagues used a technique known as Bloom filter encoding with differential privacy. They devised a suite of algorithms which deliberately introduces enough noise into the data to blur precise details to the point where they cannot be extracted from individual records, but it still allows the patterns of records of the same disease condition to be matched and clustered. The accuracy of their technique was then evaluated using North Carolina voter registration data. And the results showed the method led to a negligible error rate with a guarantee of a very high level of privacy, even on highly corrupted datasets. The technique significantly outperforms existing methods. In addition to detecting and counting rare diseases, the research has many other applications; for determining awareness of a new product in marketing, for instance, or in cybersecurity for tracking the number of unique views of particular social media posts. But it is the application to rare diseases about which the Macquarie University researchers are passionate. "There is no better feeling for a researcher than seeing the technology they've been developing having a real impact and making the world a better place," says Professor Kaafar. "In this case, it is so real and so important." The OpenTreatment Foundation partly funded the research. "The Foundation wanted to make this project completely open source from the very beginning," Dr Vatsalan adds. "So the algorithm we implemented is being published openly." The authors will present their research at the 18th ACM ASIA Conference on Computer and Communications Security (ACM ASIACCS 2023) in Melbourne on 12 July.

One year after BridgeBio and its partners won accelerated approval for liver cancer drug Truseltiq (infigratinib), the company is pulling a planned Phase III program after its partner announced plans to permanently discontinue distribution of the drug on Wednesday. The news was announced in a brief filing with the U.S. Securities and Exchange Commission. Helsinn Healthcare SA, which holds a New Drug Application for Truseltiq in the United States, announced it will withdraw the drug and the planned application with the FDA due to “business reasons.” The filing did not discuss any clinical or safety issues related to the drug. The partnership was valued at over $2.4 billion and shares of BridgeBio were down in early trading following the announcement. BridgeBio and its partners, Switzerland-based Helsinn and LianBio, were assessing Truseltiq in multiple cancer indications. As a result of the planned withdrawal, BridgeBio will shutter its ongoing Phase III PROOF-301 clinical trial of infigratinib in first-line cholangiocarcinoma. LianBio, which holds the Chinese marketing rights for Truseltiq, has also been forced to terminate its activities related to the study. Shanghai-based LianBio will no longer pursue the development and commercialization of infigratinib for cholangiocarcinoma, the company reported. Truseltiq, an oral ATP-competitive, tyrosine kinase inhibitor of FGFR, was approved in June 2021 for the treatment of patients with previously-treated locally advanced or metastatic cholangiocarcinoma (CCA) with an FGFR2 fusion or rearrangement. An Unexpected End LianBio noted in its SEC filing that it will continue to provide Truseltiq to patients in China who are currently being treated with the medication. It will do so under the Named Patient Program in Hainan Province. LianBio will also continue its ongoing Phase IIa proof-of-concept study of Truseltiq in patients with locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with FGFR2 genetic amplification and other solid tumors with FGFR alterations. Months ahead of Truseltiq’s accelerated approval, Helsinn and BridgeBio entered into a global license and collaboration agreement to commercialize the medication in the U.S. and other global markets. LianBio held marketing rights in mainland China, Hong Kong and Macau. Beyond Truseltiq, Helsinn and BridgeBio had also partnered on the development and potential commercialization of an inhibitor that targets glutathione peroxidase 4 (GPX4). That asset is expected to be used to target undisclosed difficult-to-treat tumors. The partnership also included the potential co-development of preclinical precision oncology programs that were in the portfolios of both companies.