Introduction & Objectives: ORKA-001 is a novel half-life extended monoclonal antibody targeting IL-23p19 with similar potency and epitope binding to risankizumab. ORKA-001’s extended half-life has the potential to enable once-yearly dosing, increased efficacy, and extended off-treatment remission in psoriasis. Here, 24-week results of the First in Human (FIH) Phase 1 study of ORKA-001 in healthy volunteers are presented. Materials & Methods: This Phase 1, double-blinded, placebo-controlled, randomized FIH study evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses (SAD) of ORKA-001 in 24 healthy adult volunteers. Participants were randomized 6:2 to receive a single subcutaneous (SC) dose of ORKA-001 or placebo across three ascending dose-level cohorts: 300 mg, 600 mg, and 1200 mg. Participants were admitted to a Clinical Research Unit, where they remained until Day 4 and then returned to the clinic for follow-up safety and PK assessments over one year. Results: Eight participants were dosed in each of the 3 cohorts: 6 with ORKA-001 and 2 with placebo. Baseline characteristics were typical of a healthy volunteer population. Half-life of ORKA-001 was approximately 100 days. Individual PK profiles showed no indication of anti-drug antibodies (ADAs). In an ex vivo assay, serum from subjects dosed with ORKA-001 potently inhibited IL-23-mediated STAT3 signaling for 24 weeks (study duration to date). The study remains blinded; however, no serious or severe adverse events (AEs) were reported, and no discontinuations occurred. AEs reported in >2 participants were headache, upper respiratory tract infection, and transient erythema at the injection site. All of these events were mild. No dose-dependent trends in AEs were observed. Conclusion: PK and PD results in this Phase 1 study of ORKA-001 support the potential for once-yearly dosing while maintaining trough antibody concentrations above approved IL-23 targeting antibodies like risankizumab. In addition, the PK profile supports evaluation of higher antibody exposures that may allow ORKA-001 to achieve higher rates of skin clearance than that of the current standard of care and long-term off-treatment remission in some patients. ORKA-001 was well-tolerated across all dose levels, with a favorable safety profile consistent with the IL-23p19 inhibitor class. These attributes are being further explored in an ongoing Phase 2a study, EVERLAST-A, which is evaluating efficacy and safety of ORKA-001 in adults with moderate-to-severe psoriasis.
In the first half of 2025, the Russian construction market demonstrates multidirectional trends: with investments in fixed assets growing by 4.3% in the first half of the year, the dynamics of the basic building materials output remains negative. The housing supply structure is rapidly shifting toward individual housing construction (IHC). This is shown to be changing the consumption pattern for cement and concrete, increasing the demands on logistics and shipping formats. The cost of building materials does not explain the price gap between the primary and secondary housing markets. Conclusions are drawn regarding the necessary management and technological adaptations in the industry.
Carbon capture and sequestration (CCUS) is essential for reducing greenhouse gas emissions. A critical challenge in CCUS is transporting carbon dioxide (CO2) via pipelines while mitigating corrosion and cracking risks caused by impurities such as water (H2O), sulfur dioxide (SO2), nitrogen dioxide (NO2), oxygen (O2), and hydrogen sulfide (H2S).1 This study evaluates the performance of 316L, 22Cr, S13Cr-110, 6Mo stainless steels, and 625 nickel alloy under these conditions. Oxygen presence significantly influences corrosion, particularly at the H2O/CO2 interface.2 High-PREN (Pitting Resistance Equivalent Number) materials like 6Mo, 22Cr DSS, and Alloy 625 demonstrate superior resistance, making them preferable choices for CO2 transport applications.
The purpose of this study was to determine the direct relationship of training, certification and competency variables to employee performance mediated by employee development, while the results of this study concluded that there was a direct relationship and used literature studies without research respondents and did not use statistical data processing, in this study there are many findings that can be developed again in further research by other researcher.
The PROTEUS project involves the construction of a self-propelled and floating amphibious machine for near shore geological surveys. In this context, the development of a wireline core drilling device was tackled, evolving with respect to existing models and responding to the specificities of the new application. In the preliminary phase, comparative research was carried out both through market research and through reverse engineering activities on core drill models deemed suitable for the purpose, thus identifying the functional priorities and criticalities of the existing material through the ex-post analysis of the subject elements to wear and tear. Once the requirements of the new core drilling device were formalized, the constructive layout was defined, giving priority to functions such as sample management, interlocking and rapid disengagement from the drilling actuation system. The construction details of the mechanical coupling profiles were then optimized by simulation in a multibody software environment, in order to ensure full functionality even in harsh environments, typical of the application, making an advancement with respect to the previously identified reference solutions. Finally, the executive design of the component was carried out by introducing the corrections deriving from the simulation results and considering different solutions in relation to the material adopted and its production needs through machining processes.
