CTI BioPharma (Italy)

Capillary electrophoresis (CE) often provides superior separation of macromolecules such as monoclonal antibodies (mAbs), a major biopharmaceutical class, compared with liquid chromatography. However, electropherograms frequently exhibit complex baselines and peak shapes that are not reliably handled by integration algorithms designed for chromatographic data, and manual integration is often required. Many concepts have been proposed to improve peak integration, ranging from incremental algorithmic refinements and signal-to-noise (S/N)-based approaches to artificial intelligence (AI)-driven strategies, but objective performance comparisons are not possible without shared reference data sets and agreed peak limits. To address this gap, we initiated a multinational collaboration involving industrial and academic laboratories to create a comprehensive reference data set for CE peak integration. A total of 227 challenging and practically relevant electropherograms were collected from diverse applications, converted to a standardized format, and independently integrated by multiple experts. Using dedicated software tools and a structured consensus process, mutually accepted reference integration limits were established for each data set. These reference electropherograms, together with the underlying integration rules, are now made available to the scientific community. Analysis of the reference data set identified general principles for reliable peak integration, including the importance of standardized zoom levels and consistent handling of small peaks near the noise level. The data set provides a common foundation for benchmarking commercial chromatography data systems (CDS) and for developing and validating new algorithmic and AI-based integration methods. We expect this work to speed up the development of practical, automated integration strategies for CE and that these core concepts can be applied to other separation techniques.

Introduction: Air pollution is the causative factor for considerable morbidity and premature death worldwide. This review critiques the WHO's Air Pollution Harm Reduction Strategy in Dhaka, Bangladesh, through the lens of the HBM by analysing its effectiveness and ethical implications. Materials and Methods: This critical review synthesises findings from WHO publications, peer-reviewed journals, and public health data on Dhaka's air quality management. The approach involves thematic analysis of health promotion strategies and behavioural change interventions. Discussion: The findings highlight that while the WHO strategy is successful in raising awareness and providing a policy direction, it continues to be hampered by economic barriers, weak enforcement, and absence of local engagement. HBM explains personal motivation toward cleaner practices but falls short on systemic inequities and gendered exposures. Conclusion: A multi-sectoral policy enforcement, equity-focused planning, and culturally sensitive communication are some of the basic tenets for structuring Dhaka's air pollution strategy toward sustainable impact. Strengthening community ownership and data-driven governance bridges the gap between global frameworks and local realities. Medicine Today 2026, Vol.38 (1): 137-141

The BRG/Brahma-associated factors (BAF or mSWI/SNF) family of chromatin remodeling complexes are critical regulators of gene expression and are major determinants of cancer and other diseases. Two paralog ATPases, SMARCA4 and SMARCA2 (BRG1 and BRM, respectively), provide the enzymatic activity required for chromatin remodeling. Here, we discover and characterize a novel series of compounds that potently and selectively inhibit SMARCA4/SMARCA2. Mutational and biochemical studies demonstrate that these inhibitors act through a unique mode of inhibition, distinct from reported SMARCA4/SMARCA2 inhibitors. Across a range of cancer cell lines, SMARCA4/SMARCA2 inhibition resulted in lineage-specific changes in chromatin accessibility at binding sites for key transcription factors (TFs). In uveal melanoma (UM), BAF inhibition resulted in loss of enhancer occupancy of SOX10 and MITF, two essential TFs, leading to down-regulation of the melanocytic gene expression program. In a mouse xenograft model of UM, SMARCA4/SMARCA2 inhibition was well tolerated and resulted in dose-dependent tumor regression correlating with pharmacodynamic modulation of BAF-target gene expression. These data provide the foundation for first-in-human studies of BAF ATPase inhibition as a novel therapeutic to treat TF-dependent cancers.

Abstract Background Claudin 18.2 (CLDN18.2) is a validated target in GEC, but novel approaches are needed. Givastomig/ABL111 (giva) is a first-in-class, bispecific antibody targeting tumoral CLDN18.2 and 4-1BB on adjacent T cells, preferentially activating T cells in the tumor microenvironment. Previously, the monotherapy phase 1 data showed that giva was safe and well tolerated in heavily pretreated GEC patients (pts). Here we report updated safety, efficacy, and biomarker data in GEC. Methods The study included dose escalation and dose expansion cohorts. During escalation, pts with solid tumors irrespective of CLDN18.2 expression received giva intravenously every 2 weeks (Q2W) across 8 dose levels (0.1-15 mg/kg), and every three weeks (Q3W) at 18 mg/kg. During expansion, CLDN18.2-positive (CLDN18.2+, ≥1% of tumor cells with ≥1+ intensity by immunohistochemistry) GEC pts were included. Differences in objective response rate (ORR) and disease control rate (DCR) between CLDN18.2-high pts (≥ 75% tumor cells of IHC 2+/3+) and CLDN18.2-low pts were evaluated by Chi-square test. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards. Outcomes for CLDN18.2+ GEC pts at doses ≥ 5 mg/kg are reported here. Results As of June 10, 2025, 45 pts with GEC received giva at 5 mg/kg (n=7), 8 mg/kg (n=5), 12 mg/kg (n=21), and 15 mg/kg (n=6) Q2W and 18 mg/kg Q3W (n=6). Pts had received a median of 3 prior therapies, including 74% with prior programmed death-(ligand) 1 inhibitor. No new safety signal was identified with longer follow up. No dose limiting toxicities were observed. Common treatment-related adverse events (≥15%, any grade/grade 3) included anemia (27%/9%), white blood cell count decrease (22%/7%), nausea (20%/2%), and ALT increase (16%/2%), AST increase (16%/4%). Partial responses (PR) were observed in 8 pts (1 PR each at 5 and 8 mg/kg, 4 PRs at 12 mg/kg, and 2 PRs at 18 mg/kg) with an ORR of 18%. CLDN18.2 expression in responders ranged from 11% (1+, 10%; 2+, 1%) to 100% (2+, 10%; 3+, 90%). Stable disease was observed in 14 pts (DCR 49%). 2 (4%) pts are ongoing, with 1 PR at 8 mg/kg at 33 months (mo) and 1 PR at 18 mg/kg at 10 mo. The median PFS (mPFS) and median OS (mOS) are 2.96 mo (95% CI 1.71-3.91) and 7.49 mo (95% CI 4.96-12.5), respectively. There is no statistical difference in ORR, DCR, PFS, or OS between CLDN18.2-high pts (n=21) and CLDN18.2-low pts (n=24): ORR 19% vs. 17% (p=1.00), DCR 57% vs. 42% (p=0.46), mPFS 3.68 mo vs. 1.84 mo, PFS hazard ratio (HR) 0.87 (p=0.67), and mOS 7.49 mo vs. 7.49 mo, OS HR 0.88 (p=0.74), respectively. Conclusions Giva was well tolerated up to 15 mg/kg Q2W and 18 mg/kg Q3W and continues to show encouraging monotherapy activity in heavily pre-treated GEC pts with a wide range of CLDN18.2 expression. Giva may have the ability to target pts with lower CLDN18.2 expression compared with other CLDN18.2 agents and is currently being tested in 1L GEC in combination with immunochemotherapy (NCT04900818). Citation Format: Samuel J. Klempner, Lin Shen, Farshid Dayyani, Jeremy Kratz, Xinjun Liang, Funan Liu, Zenning Wang, Laura Feller, Eugenia Girda, Hongming Pan, Sunnie Kim, Yanhong Deng, Ting Deng, Tianshu Liu, John Powderly, Kristen Spencer, Reva Schneider, Jordan Berlin, Claire (Cong) M. Xu, Christoph M. Ahlers, Xuejun M. Liu, Peter Sabbatini, Jinyoung Park, Yangmi Lim, Juyeun Jeon, Yuan Meng, Geoffrey Ku. Updated Safety, Efficacy and Biomarker Analysis from the Phase I Study of Givastomig, a Novel Claudin 18.2/4-1BB Bispecific Antibody, in Claudin 18.2 Positive Advanced Gastroesophageal Carcinoma (GEC) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr B016.

Abstract BackgroundGenome-wide off-target nomination and screening sequencing methods, such as synthetic oligonucleotide-based sequencing and whole genome-based sequencing, evaluate the precision and safety of gene-editing technologies. However, there remains a lack of comprehensive bioinformatics tools for analyzing the sequencing data generated by off-target nomination assays for various gene editors, including Cas9, Cas12a, and base editors.ResultsWe introduce a Sequencing Analysis Toolkits for Off-target Nomination (SANTON) for the identification and quantification of potential off-target sites using datasets generated from synthetic oligonucleotide-based sequencing and whole genome-based sequencing (e.g., Digenome-seq) methods. By applying SANTON to a Cas9 treated oligo synthesization-based sequencing data, a comprehensive set of potential off-target sites are evaluated in which the top off-target sites displayed highly constituency with a published study usingin vivomethod (e.g, GUIDE-seq). Utilizing SANTON to previously published Digenome-seq datasets, we identified more potential off-target regions than previous studies, including ones showing significantly higher cleavage level than the on-target site. To the best of our knowledge, SANTON is the first public package capable of analyzing synthetic oligonucleotide-based sequencing data and the first to specific optimized for the analysis of whole genome-based sequencing analysis for Cas12a and base editors. We demonstrated the capability of SANTON to effectively analyze complex cleavage patterns by a diverse editing system.ConclusionsSANTON provides a powerful computational solution to support genome editing research, facilitating more reliable and comprehensive off-target profiling.