Apocare Pharma (Germany)

The impacts of agricultural, environmental and climate change policies in Europe are investigated using the CAPRI (Common Agricultural Policy Regionalised Impact) model. Although the model runs at a regional level, primarily NUTS2, the underlying data have been spatially disaggregated to finer scale units called 'Farm Structure Units'. In this study we present these spatially disaggregated layers of agri-environmental variables for a time series from 2000 to 2018. This harmonized and spatially consistent data set includes crop types (area, yield), livestock types (totals and densities) and various parameters associated with nitrogen application and losses. These data can be used to calculate nitrogen budgets as well as providing inputs to biogeochemical or land management models.

IntroductionThe extension of human longevity has intensified the search for biomarkers that capture not only chronological age but also biological aging and functional healthspan. Among molecular candidates, microRNAs (miRNAs) have emerged as promising regulators and indicators of aging-related processes. In this pilot study, we explored whether selected circulating miRNAs could serve as potential biomarkers of biological age and lifestyle-associated aging dynamics.MethodsBased on current literature, we focused on three miRNAs—miR-24, miR-21, and miR-155—previously linked to inflammation, senescence, and metabolic regulation. Capillary blood samples from a heterogeneous adult cohort were analyzed using quantitative PCR. ΔCt values were integrated into a composite “miRNA-3Age” model through multivariate regression analysis to estimate biological age. Associations between lifestyle variables (diet, exercise, stress, and smoking) and miRNA-based biological age were examined.ResultsThe miRNA-3Age model predicted biological age with moderate correlation to chronological age and revealed variability consistent with individual health profiles. Participants with favorable lifestyle factors (e.g., frequent consumption of fish, whole grains, and green tea; regular exercise) tended to exhibit lower miRNA-3Age estimates, whereas stress and smoking were associated with higher predicted biological age.DiscussionOur exploratory data suggest that integrating multiple miRNA signals may enhance the sensitivity of biological age estimation compared to single-biomarker approaches. However, variability within the small sample highlights the need for larger, longitudinal datasets to confirm predictive validity and to disentangle causal links between lifestyle, miRNA expression, and aging biology.ConclusionThis pilot study supports the feasibility of miRNA-based biological age modeling and identifies miR-24, miR-21, and miR-155 as promising components of a composite biomarker framework. The miRNA-3Age model provides a preliminary step toward a scalable, lifestyle-sensitive aging metric that warrants validation in diverse populations.

Orelabrutinib is a novel, small molecule, selective irreversible Bruton's tyrosine kinase inhibitor. The aim of this study was to evaluate the efficacy and safety in patients with refractory or relapsed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). This is single-arm, multi-center, open-label, phase 2 study in 80 eligible Chinese patients, who were treated with monotherapy of orelabrutinib at 150 mg once daily. Overall response rate evaluated by an independent review committee was the primary endpoint, and secondary endpoints include progression-free survival, overall survival, and safety. Independent review committee assessed overall response rate was 92.5% (74/80); complete response 21.3% (17/80), partial response 60.0% (48/80), partial response with lymphocytosis 11.3% (9/80). At a 32.3-month median follow-up, the median progression-free survival had not been achieved, while the 30-month progression-free survival rate and overall survival rates were 70.9% (95% confidence interval [CI], 59.5-79.6) and 81.3% (95% CI, 70.8-88.2), respectively. Orelabrutinib also revealed substantial response in patients with high prognostic risks: overall response rates of patients carrying positive TP53 mutational status or del(17p), del(11q), as well as unmutated immunoglobulin heavy-chain variable region gene were 100%, 94.7%, and 93.9%, respectively. Most adverse events were in low grade, with 86.8% of AEs being Grade 1 or 2. Nearly 67% of patients were still receiving orelabrutinib after almost a 3-year follow-up. In conclusion, Orelabrutinib demonstrated compelling efficacy as well as safety profiles, with a noteworthy number of patients obtaining complete response in refractory or relapsed CLL/SLL.

Introduction: Orelabrutinib is a novel and highly selective irreversible BTK inhibitor. We previously reported that orelabrutinib had high bioavailability with ∼100% BTK occupancy at 24 hours at 150 mg daily dosing regimen and had demonstrated excellent safety and efficacy profiles in a phase II trial of r/r CLL/SLL. Here we present an updated result following the extended time of treatment. Method: This is an open-label, multicenter, phase II study to evaluate the safety and efficacy following an oral daily administration of orelabrutinib. Responses were assessed per 2008 IWCLL criteria. Results: A total of 80 patients with r/r CLL/SLL were enrolled. Eligible patients received ≥1 prior treatment with median age of 60.0 years. There are 70% of patients for Rai stage 3-4 disease, 22.5% for del(17p) and/or TP53 mutation, 41.3% for unmutated IGHV and 23.8% for del(11q). The median follow-up time was 25.6 months, with 71.3% remaining on study treatment. The efficacy results were evaluated by both IRC and investigators, with the ORR of 92.5 % with 16.3% CR/CRi, 65.0% PR and 11.3% PR-L by IRC, and the ORR of 93.8% with 21.3% CR/CRi, 61.3% PR, and 11.3% PR-L by investigators. These results revealed high concordance rate for overall response assessments between IRC and investigator. Median time for achieving first response was 1.87 months. The median DOR and PFS were not reached. The estimated 18-month DOR was 77.2%, and PFS was 78.7% by IRC. The ORR was 100% in patients with Del(17p) and/or TP53 mutation. The ORR was 94.7% for Del(11q)) and 93.9% for unmutated IGHV. Comparing to the previous CR/CRi rate of 8.8% and 10.0% reported at median follow up of 14.3 months, the updated CR/CRi rate had achieved 21.3% and 16.3% by investigator and IRC assessment, respectively. Orelabrutinib showed a significant higher CR/CRi rate in r/r CLL/SLL comparing to other BTK inhibitors at a similar median follow-up period. Extended follow-up analysis did not reveal new safety nor toxicity concerns. Similar to the previous reported safety results, most AEs were mild to moderate. The most frequent AEs were hematological toxicities, upper respiratory tract infection, pneumonia and hypokalemia. No case of atrial fibrillation nor secondary malignancy was reported, no patient was observed for ≥3 grade hypertension and only one patient had ≥3 grade diarrhea. Major hemorrhage was reported in 2 patients, one with intracranial hemorrhage (65-year old patient with >10 years hypertension) and the other with vitreous hemorrhage which was assessed as unlikely related to the treatment of orelabrutinib. Conclusion: This updated study result further confirms that orelabrutinib is efficacious in treating r/r CLL patients with a significant higher CR rate, durable response and improved safety profiles. Orelabrutinib provides a favorable therapeutic choice for patients with r/r CLL/SLL and a potential best candidate for the combination therapy. EA – previously submitted to regional or national meetings (up to 1000 attendees) The research was funded by: Beijing InnoCare Pharma Tech Co., Ltd Keywords: Chronic Lymphocytic Leukemia (CLL) Conflicts of interests pertinent to the abstract R. Zhao Employment or leadership position: Employment B. Zhang Employment or leadership position: Employment

Currently, drug repurposing is an alternative to novel drug development for the treatment of COVID-19 patients. The antimalarial drug chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are currently being tested in several clinical studies as potential candidates to limit SARS-CoV-2-mediated morbidity and mortality. CQ and HCQ (CQ/HCQ) inhibit pH-dependent steps of SARS-CoV-2 replication by increasing pH in intracellular vesicles and interfere with virus particle delivery into host cells. Besides direct antiviral effects, CQ/HCQ specifically target extracellular zinc to intracellular lysosomes where it interferes with RNA-dependent RNA polymerase activity and coronavirus replication. As zinc deficiency frequently occurs in elderly patients and in those with cardiovascular disease, chronic pulmonary disease, or diabetes, we hypothesize that CQ/HCQ plus zinc supplementation may be more effective in reducing COVID-19 morbidity and mortality than CQ or HCQ in monotherapy. Therefore, CQ/HCQ in combination with zinc should be considered as additional study arm for COVID-19 clinical trials.

The increasing incidence of implant-associated infections induced by Staphylococcus aureus (SA) in combination with growing resistance to conventional antibiotics requires novel therapeutic strategies. In the current study we present the first application of the biofilm-penetrating antimicrobial peptide lysostaphin in the context of bone infections. In a standardized implant-associated bone infection model in mice beta-irradiated lysostaphin-coated titanium plates were compared with uncoated plates. Coating of the implant was established with a poly(D,L)-lactide matrix (PDLLA) comprising lysostaphin formulated in a stabilizing and protecting solution (SPS). All mice were osteotomized and infected with a defined count of SA. Fractures were fixed with lysostaphin-coated locking plates. Plates uncoated or PDLLA-coated served as controls. All mice underwent debridement and lavage on Days 7, 14, 28 to determine the bacterial load and local immune reaction. Fracture healing was quantified by conventional radiography. On Day 7 bacterial growth in the lavages of mice with lysostaphin-coated plates showed a significantly lower count to the control groups. Moreover, in the lysostaphin-coated plate groups complete fracture healing were observed on Day 28. The fracture consolidation was accompanied by a diminished local immune reaction. However, control groups developed an osteitis with lysis or destruction of the bone and an evident local immune response. The presented approach of terminally sterilized lysostaphin-coated implants appears to be a promising therapeutic approach for low grade infection or as prophylactic strategy in high risk fracture care e.g. after severe open fractures.

Circulating tumor cells (CTC) refer to cells that detach from a primary tumor or metastatic site, circulate in the peripheral blood and may form metastasis. CTC represent a 'liquid biopsy' that can be used to tailor treatment for individual patients. CTC are however rare and can only be obtained for further characterization in a small fraction of patients.