PeopleBio (South Korea)

Craniofacial bone reconstruction presents significant clinical challenges due to the region's complex anatomy and the need to restore both structural integrity and aesthetic function. This study aimed to enhance bone regeneration at graft sites through the development of an osteoconductive bioactive glass-polymer composite for patient-specific implant (PSI) applications. Composite constructs were fabricated via extrusion-based 3D printing using varying weight ratios of bioactive glass ceramic (BGS-7) and poly(ε-caprolactone) (PCL): 2:8, 4:6, 4.5:5.5, and 5:5. Printing parameters were optimized for each formulation to ensure consistent material flow and structural fidelity. Comprehensive characterization included morphological and elemental analysis via scanning electron microscopy/energy-dispersive X-ray spectroscopy, mechanical testing (compressive, flexural, and tensile), and biological evaluation and osteogenic differentiation of human placental stem cells. Higher BGS-7 content correlated with increased incorporation of phosphate, silicon, and calcium, contributing to enhanced mechanical properties and osteogenic potential. The constructs supported high cell viability, promoted cell adhesion and spreading, and induced osteogenic differentiation, as evidenced by calcium deposition and upregulation of key markers. The high-content BGS-7/PCL (5:5) formulation demonstrated optimal printability and bioactivity and was successfully used to fabricate anatomically accurate, human-scale structure. These findings highlight the potential of BGS-7/PCL composites as scalable, biocompatible, and osteoconductive platforms for craniofacial PSI applications.

BackgroundSynuclein aggregates are a hallmark of synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), contributing to their pathogenesis. Current detection methods rely on cerebrospinal fluid and tissue samples, limiting clinical utility. A robust plasma‐based assay is needed for non‐invasive biomarker development. This study validates the constant shake‐induced conversion (CSIC) method for quantifying plasma synuclein aggregates and evaluates its ability to distinguish PD patients from healthy controls (HCs), demonstrating broader applicability across synucleinopathies.MethodsThe CSIC method was assessed using synuclein seeds incubated for six days. Plasma samples from PD and HC patients were analyzed, and the CSIC method was verified based on synuclein depletion, quantification with the enzyme‐linked immunosorbent assay, and confirmation using Western blotting. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) analysis, while Spearman correlation coefficients (r) were used to evaluate the association between clinical features and synuclein aggregates. Repeatability and reproducibility were tested by three experimenters.ResultsCSIC effectively amplified synuclein aggregates in plasma, with a significant difference observed between the PD and HC groups (p < 0.0001). Synuclein depletion confirmed the specificity of CSIC, while ROC analysis produced an area under the curve of 0.91, with a sensitivity of 80.95% and a specificity of 85% when distinguishing PD patients from HCs. The proposed method also had a coefficient of variation (CV) of less than 10% for repeatability and a CV of around 20% for reproducibility over 48 h. CSIC had a strong clinical correlation with the Hoehn and Yahr stage (r = 0.69), the Unified Parkinson's Disease Rating Scale (r = 0.68), and the Montreal Cognitive Assessment score (r = –0.47).ConclusionThis study is the first to demonstrate the detection of plasma synuclein aggregates using CSIC, addressing a critical diagnostic gap in synucleinopathies. The ability of CSIC to differentiate PD patients from HCs highlights its potential as a non‐invasive diagnostic tool that advances the use of plasma synuclein aggregates in the diagnostic and therapeutic monitoring of PD and related disorders.

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.

INTRODUCTIONAlzheimer's disease (AD) is now diagnosed biologically. Since subjective cognitive decline (SCD) may indicate preclinical AD, assessing AD‐biomarkers is crucial. We investigated cognitive and neurodegenerative trajectories in SCD over 24 months based on biomarker positivity, and evaluated the predictive value of plasma biomarkers.METHODSThe CoSCo prospective cohort included older adults with SCD. Participants were categorized into high‐ and low‐risk groups based on plasma biomarkers (amyloid beta [Aβ] 42/40, phosphorylated tau 181 [p‐tau181], and glial fibrillary acidic protein [GFAP]), and magnetic resonance imaging (MRI) findings to compare outcomes.RESULTSHigh‐risk SCDs (n = 23, 23%) revealed greater decline in general cognition, memory recall, frontal function, and hippocampal volumes compared to low‐risk SCDs. Combined scores of plasma and MRIs yielded the best predictions compared with other biomarker categories.DISCUSSIONSCD participants with high‐risk experience faster cognitive and neurodegenerative declines. A combination of plasma biomarkers and MRIs could be used for screening and prognosis.HighlightsThis is part of a multicenter prospective cohort study in Korea.We investigated cognitive and atrophic trajectories in SCD over 24 months.High risk SCDs revealed greater cognitive decline and hippocampal atrophy.Integration of plasma and MRIs yielded better predictions than other categories.Risk stratification using plasma and MRIs can be used for screening and prognosis.

PurposeAmong other emerging amyloid-targeting blood-based biomarkers, Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) measures dynamic changes in concentration of oligomeric amyloid-β (OAβ), which is considered the main pathogenic culprit of Alzheimer’s disease (AD), in plasma after spiking with synthetic amyloid-β (Aβ). We aimed to investigate the predictability of MDS-OAβ on amyloid positron emission tomography (PET) positivity.Patients and MethodsA total of 96 subjects who visited Seoul National University Bundang Hospital for medical check-up complaining of cognitive decline and had undergone extensive medical assessment were recruited. Amyloid statuses were dichotomized into positive or negative based on visual assessment of amyloid PET. Plasma OAβ concentration was measured by MDS-OAβ. In the previous validation study, 0.78ng/mL was established as the cut-off value and the plasma OAβ concentration higher than or equal to the cut-off value was defined as MDS-OAβ positive.ResultsMDS-OAβ positivity could discriminate amyloid PET positivity with the AUC value of 0.855 (95% CI 0.776–0.933). Adding MDS-OAβ positivity to prediction models including age, MMSE score, and APOE ε4 status improved performance up to the AUC value of 0.926 (95% CI 0.871–0.980).ConclusionThe Aβ oligomerization tendency in plasma could predict amyloid PET positivity with high performance, and, when it is combined with age, MMSE score, and APOE ε4 status, predictability was improved substantially. This suggests the potential of MDS-OAβ as a useful initial stage test in the clinical and research fields of AD.

The increasing prevalence of Alzheimer’s disease (AD) has become a global phenomenon presenting serious social and health challenges. For detecting early molecular changes in the disease, several techniques to measure varied species of amyloid beta in the peripheral blood have been recently developed, but the efforts to associate them with cognitive assessments have yet to produce sufficient data. We prospectively collected participants from the consecutive population who visited our center for brain health screening. In total, 97 participants (F:M = 58:39) aged 69.4 ± 7.52 were assessed. Participants performed the Korean version of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD-K), the clinical dementia rating (CDR), plasma oligomeric amyloid-β (OAβ) level tests, routine blood tests, ApoE genotype, and brain MRI. Among total population, 55.7% had a CDR of 0, and 40.2% had a CDR of 0.5. The results showed that word memory and word recall, and the total scores of the CERAD-K were negatively correlated with the plasma OAβ level. With a cut-off value of 0.78 ng/mL for the OAβ level and a −1.5 standard deviation of age/sex/education adjusted norms for the CERAD-K; naming, word memory, word recall, word recognition, and total score were significantly correlated with the OAβ level. No correlation between the OAβ level and mini-mental status examination was found. Our results demonstrate that the level of plasma OAβ was well correlated with the measure of cognitive function through the CERAD-K in the field data collected from consecutive populations. Studies on longitudinal comparisons with large cohorts will further validate the diagnostic value of plasma OAβ as a useful biomarker for screening AD and predicting progression.

BackgroundSoluble amyloid-β (Aβ) oligomers are the major toxic substances associated with the pathology of Alzheimer’s disease (AD). The ability to measure Aβ oligomer levels in the blood would provide simple and minimally invasive tools for AD diagnostics. In the present study, the recently developed Multimer Detection System (MDS) for AD, a new enzyme-linked immunosorbent assay for measuring Aβ oligomers selectively, was used to detect Aβ oligomers in the plasma of patients with AD and healthy control individuals.MethodsTwenty-four patients with AD and 37 cognitively normal control individuals underwent extensive clinical evaluations as follows: blood sampling; detailed neuropsychological tests; brain magnetic resonance imaging; cerebrospinal fluid (CSF) measurement of Aβ42, phosphorylated tau protein (pTau), and total tau protein (tTau); and 11C-Pittsburgh compound B (PIB) positron emission tomography. Pearson’s correlation analyses between the estimations of Aβ oligomer levels by MDS and other conventional AD biomarkers (CSF Aβ42, pTau, and tTau, as well as PIB standardized uptake value ratio [PIB SUVR]) were conducted. ROC analyses were used to compare the diagnostic performance of each biomarker.ResultsThe plasma levels of Aβ oligomers by MDS were higher in patients with AD than in normal control individuals, and they correlated well with conventional AD biomarkers (levels of Aβ oligomers by MDS vs. CSF Aβ42, r = −0.443; PIB SUVR, r = 0.430; CSF pTau, r = 0.530; CSF tTau, r = 0.604). The sensitivity and specificity of detecting plasma Aβ oligomers by MDS for differentiating AD from the normal controls were 78.3% and 86.5%, respectively. The AUC for plasma Aβ oligomers by MDS was 0.844, which was not significantly different from the AUC of other biomarkers (p = 0.250).ConclusionsPlasma levels of Aβ oligomers could be assessed using MDS, which might be a simple, noninvasive, and accessible assay for evaluating brain amyloid deposition related to AD pathology.

The Cell-Dyn 4000 automated hematology analyzer (CD4000) has the ability to detect malaria patients, but it remained unclear whether it could detect persistent malaria post-treatment. To investigate this, we used the CD4000 to evaluate 68 Korean patients with Plasmodium vivax malaria, and control groups of 50 patients with fever and 50 asymptomatic patients. The results from the instrument-generated scatter plot (derived by laser light depolarization) were compared with microscopy results. During the initial diagnosis, the sensitivity of the CD4000 in detecting malaria was 91.2%. On day 3 of follow-up, the CD4000 results matched those from microscopy by 96.7%. Malaria was not detected by either method beyond 14 days post-presentation. Interestingly, the atypical depolarizing events, which typify the presence of malaria in the analyzer, were highly correlated with the levels of parasitaemia in serially diluted samples of the leucocyte-depleted blood, and the CD4000 detected parasites down to the level of 288 +/- 17.7/microl. Our findings suggest that the phenomenon of atypical light depolarization could be influenced by parasitaemia levels, and be used as a screening method for P. vivax malaria patients, as well as for the therapeutic monitoring.