DP1

Owkin announced on Thursday the launch of ATLANTIS, an AI-powered multimodal patient data discovery programme that analyses and extracts knowledge from complex medical data, including imaging, genomics, clinical records and more. The information gleaned from ATLANTIS will be leveraged by Owkin's "AI co-pilot," Owkin K, to accelerate drug discovery and diagnostics.According to the company, ATLANTIS was designed to overcome the challenge of data being siloed across different institutions and departments. It noted that while AI can drive innovation by utilising rich, unified datasets, this becomes a challenge when data is fragmented and inaccessible.ATLANTIS will map data in 11 therapeutic areas, including seven in oncology: non–small-cell lung cancer, head and neck squamous cell carcinoma, breast cancer, prostate cancer, ovarian cancer, pancreatic cancer and multiple myeloma; three in immunology: ulcerative colitis, Crohn's disease and systemic lupus erythematosus; and one in neurology: Alzheimer's disease.A consortium of 20 international healthcare institutions has come together with ATLANTIS to bolster their AI research efforts and derive deeper insights from their multimodal data, fueling advancements in medical discovery. In a post on LinkedIn, Owkin CEO Thomas Clozel named a number of these institutions, including Cooper University Health Care, the Balearic Islands Health Research Institute Foundation, the Vall d'Hebron Research Institute, CuriMeta Inc., Washington University in St. Louis, The Girona Biomedical Research Institute, The Royal Marsden NHS Foundation Trust, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Leipzig University, Sheba Medical Center, Aster Insights and Navarrabiomed."Owkin is committed to fostering collaboration between data scientists and patient data to achieve unparalleled insights and innovation," said Agathe Arlotti, SVP of Partnerships at Owkin. "By combining our AI expertise with leading healthcare partners, we are creating a patient data network that pushes the boundaries of biomedical research. Together, we are fueling breakthroughs for patients."Initiated in September 2024, ATLANTIS is expected to be complete by May 2025. Last month, Owkin dosed the first cancer patient in a Phase I trial with OKN4395, an AI-developed triple inhibitor of EP2/EP4 and DP1. Once complete, ATLANTIS could power similar discoveries with novel data supplied to Owkin K. The tech bio also announced a partnership with fellow generative AI drug discovery firm Absci last month, combining platforms to accelerate the discovery and design of novel therapeutics.

PARIS, France I January 30, 2025 I Owkin , the first end-to-end AI-biotech that uses agentic AI to revolutionize drug discovery, development, and diagnostics, today announced that the first patient has been dosed in its Phase I clinical trial of OKN4395 on January 22, 2025. OKN4395 builds upon well-characterized EP2/EP4 inhibition, through a newly identified and equipotent inhibition of DP1. The clinical significance of this first-in-class triple inhibition is being evaluated in this trial. AI-optimized study design Owkin’s proprietary K1.0 Operating System was instrumental in advancing OKN4395 from asset selection through to clinical development. By building a detailed biological understanding of the EP2/EP4/DP1 targets and their complex mechanisms of action, Owkin’s AI operating system was used to optimize the clinical development strategy. The program integrates Owkin’s expertise in AI-driven indication selection, external control arms (digital twins) for early anti-tumor activity insights in Phase I, and biomarker-led patient subtyping to enhance the probability of clinical success. Thomas Clozel, MD, CEO & Co-founder of Owkin, said: “OKN4395 reflects not only a decade of discovery efforts by Idorsia and its collaborators but also exemplifies the transformative power of Owkin’s K1.0 Operating System. This milestone underscores our ability to rapidly translate a promising asset into an AI-optimized clinical program.” A first-in-class asset: OKN4395 Prostaglandins E 2 and D 2 (or PGE 2 , PGD 2 ) are hormone-like molecules produced naturally in the body, and are the natural ligands for prostanoid receptors EP2, EP4, and DP1, respectively. The PGE 2 /EP2/EP4 and PGD 2 /DP1 pathways are both known to be immunosuppressive 1,2 . Well-described in oncology, hyperactivity of the PGE 2 /EP2/EP4 pathway in certain cancers allows them to avoid the immune system’s effector mechanisms, leading to progression and resistance through tumor growth or metastasis 1 . OKN4395 is the first compound in the clinic to selectively inhibit EP2, EP4, and DP1 receptors. This novel mechanism offers the potential to restore immune function, providing transformative treatment options for patients with advanced solid tumors. The INVOKE Study (OKN-4395-121) INVOKE is a global, multicenter, Phase Ia/1b, first-in-human, open-label trial evaluating OKN4395 in patients with advanced solid tumors. Phase Ia primarily assesses safety and tolerability through dose escalation of OKN4395 as both a monotherapy and in combination with pembrolizumab. Phase Ib will expand into a further four cohorts, and assess preliminary anti-tumor activity, as well as safety and extensive exploratory analyses. References SOURCE: Owkin

KANAZAWA, Japan, Feb. 16, 2024 /PRNewswire/ -- In a study recently published in Nature Genetics, researchers from Nano Life Science Institute (WPI-NanoLSI), Kanazawa University explore chromatin accessibility, i.e., endogenous access pathways to the genomic DNA, and its use as a tool for gene editing. Our DNA is protected from unwanted external modifications by forming structures called nucleosomes that consist of threads of DNA wound around chunks of special proteins known as histones. This unique coiled shape prevents the access of undesirable molecules to a cell's DNA. However, for vital genetic functions—such as DNA repair—the right set of proteins require access to these DNA fragments. This phenomenon known as 'chromatin accessibility' involves a privileged set of protein molecules, many of which are still unknown. Now, researchers from Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, led by Yusuke Miyanari, have used advanced genetic screening methods to unravel chromatin accessibility and its pathways. For the investigation the team used a combination of two technologies—CRISPR screening and ATAC-see. While the former is a method to suppress the function of a desired set of genes, the latter is a means to identify which ones are essential for chromatin accessibility. Thus, using this method all genes playing a crucial role in chromatin accessibility could be pinned down. With the help of these assays, novel pathways and individual players involved in chromatin accessibility were uncovered—some playing a positive role and some negative. Of these, one particular protein, TFDP1, showed a negative effect on chromatin accessibility. When it was suppressed, a significant increase in chromatin accessibility was observed, accompanied by nucleosome reduction. A deeper dive into the mechanism of TFDP1 revealed that it functions by regulating the genes responsible for production of certain histone proteins. The team then focused their study towards exploring biotechnological applications of their findings. After suppressing TFDP1, two different approaches were tried. The first approach involved gene editing using the CRISPR/Cas9 tool. This revealed that deletion of TFDP1 made the gene editing process easier. Now, most chromatin accessibility occurs in nucleosome-depleted regions or NDRs. However, by suppressing TFDP1 chromatin accessibility occurred not only in NDRs but across other regions as well. Secondly, the depletion of TFDP1 aided the process of converting regular cells into stem cells, a massive step forward in cellular transformation. This study identified new chromatin accessibility pathways and channels for exploring its potential even further. "Our study shows the significant potential to manipulate chromatin accessibility as a novel strategy to enhance DNA-templated biological applications, including genome editing and cellular reprogramming," conclude the researchers. Background CRISPR screening: CRISPR screening is a large-scale tool used to find genes involved in a particular function. In this method, genes from the entire genome can be deleted one at a time to investigate which ones play a role in any target pathway. The mechanisms and roles of the genes narrowed down are then understood further using biological assays. In this study the genes identified by CRISPR screening were subjected to ATAC-see to confirm their involvement with chromatin accessibility. ATAC-see: Transposase-Accessible Chromatin with visualization (ATAC-see) is a technique whereby accessible DNA locations can be visualized and quantified. ATAC-see involves using an enzyme to insert fluorescent proteins into the DNA at accessible sites. This technique works within nucleosome-depleted regions but also beyond these regions. Hence, when such sites were visualized after running CRISPR screening, the researchers could understand which genes were affecting chromatin accessibility directly. Reference Satoko Ishii, Taishi Kakizuka, Sung-Joon Park, Ayako Tagawa, Chiaki Sanbo, Hideyuki Tanabe, Yasuyuki Ohkawa, Mahito Nakanishi, Kenta Nakai, Yusuke Miyanari. Genome-wide ATAC-see screening identifies TFDP1 as a modulator of global chromatin accessibility. Nature Genetics, 2024. Published Feb 15, 2024 DOI ：10.1038/s41588-024-01658-1 Related figures Figure 1. a. Screening results of the players involved in chromatin accessibility analyzed by ATAC-see. b. Successful reprogramming to stem cells (indicated by presence of TRA-1-60) after depletion of TFDP1 (right). © 2024 Ishii, et al., Nature Genetics Contact Hiroe Yoneda Senior Specialist in Project Planning and Outreach NanoLSI Administration OfficeNano Life Science Institute (WPI-NanoLSI) Kanazawa University Kakuma-machi, Kanazawa 920-1192, Japan Email: [email protected] Tel: +81 (76) 234-4555 About Nano Life Science Institute (WPI-NanoLSI), Kanazawa University Understanding nanoscale mechanisms of life phenomena by exploring "uncharted nano-realms." Cells are the basic units of almost all life forms. We are developing nanoprobe technologies that allow direct imaging, analysis, and manipulation of the behavior and dynamics of important macromolecules in living organisms, such as proteins and nucleic acids, at the surface and interior of cells. We aim at acquiring a fundamental understanding of the various life phenomena at the nanoscale. About the World Premier International Research Center Initiative (WPI) The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS). See the latest research news from the centers at the WPI News Portal: Main WPI program site: About Kanazawa University As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities. The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas. SOURCE Kanazawa University