Johnson & Johnson (Brazil)

Amivantamab is an EGFR-MET bispecific antibody approved as an intravenous formulation for EGFR-mutated advanced non-small cell lung cancer (NSCLC). Intravenous delivery is frequently associated with infusion-related reaction (IRRs), which require adopting slow infusion rates and splitting the first dose over 2 days. The PALOMA study assessed the safety and feasibility of subcutaneous amivantamab administration and identified the formulation and recommended phase II doses (RP2Ds) for multiple dosing schedules. PALOMA is a phase Ib dose-escalation study in 158 participants with advanced solid malignancies. Primary objectives included pharmacokinetics, safety, and determining RP2Ds for every-2-week (Q2W), every-3-week (Q3W), and every-4-week (Q4W) administration. The safety profile of subcutaneous amivantamab was largely consistent with intravenous monotherapy; most common toxicities reflected on-target EGFR/MET inhibition. Subcutaneous amivantamab resulted in meaningfully shorter administration time (≤ 10 minutes vs. 2.3 hours for intravenous beyond cycle 3) and lower incidence and severity of IRRs versus historical intravenous data, which eliminates the need for split-dose administration. Pharmacokinetic analyses and population pharmacokinetic modeling/simulation were used to estimate subcutaneous amivantamab RP2Ds of 1600 mg (2240 mg, ≥ 80 kg), 2400 mg (3360 mg, ≥ 80 kg), and 3520 mg (4640 mg, ≥ 80 kg) for Q2W, Q3W, and Q4W schedules, respectively. The observed efficacy was consistent with intravenous amivantamab monotherapy. Subcutaneous amivantamab administration substantially reduced IRRs, obviating the need for prolonged infusions and 2-day split-dosing at first administration. The identified RP2Ds for subcutaneous amivantamab are implemented in ongoing studies evaluating amivantamab regimens in NSCLC, colorectal cancer, and head and neck squamous cell carcinoma.

172 Background: Pasritamig is a first-in-class bispecific antibody T-cell engager that simultaneously binds human kallikrein 2 (KLK2) on PC cells and CD3 receptor complexes on T cells. Tolerable safety profile and promising anti-tumor activity was reported for US & EU population. We report results for the Asian mCRPC population from a first-in-human study (NCT04898634) evaluating pasritamig in patients with advanced PC. Methods: The RP2D dose schedule of 3.5mg (step-up dose 1)-18mg (step-up dose 2)-300mg IV Q6W was administered. Pre-medication with dexamethasone (16 mg) was implemented for step-up and first treatment dose. The primary objective was safety. Secondary objectives included preliminary antitumor activity, PK and PD. Results: As of July 4, 2025, 22 Asian patients (17 Chinese, 5 Japanese, median [range] age 69 [52-85] years), with a median of 3 prior therapies (range 2-6; 100.0% ARPI, 95.5% taxane, 22.7% PARPi, 4.5% RLT), received at least 1 pasritamig dose. Fifteen patients had bone and/or lymph node metastasis only while the other 7 patients had visceral metastasis. No DLTs, pasritamig-related deaths or treatment discontinuations were reported. Sixteen (72.7%) patients reported ≥1 treatment-related AE (TRAE), and 8 (36.4%) patients experienced Grade ≥3 TRAE. Most (7/8) Grade ≥ 3 TRAEs were cytopenia (5 lymphopenia, 2 anemia), of which the majority (5/7) already had Grade 2 cytopenia at baseline. The other Grade 3 TRAE was dermatitis, which recovered in 22 days with steroid treatment. Two (9.1%) CRS cases were reported with the severity of Grade 1. No infusion-related reactions or ICANS were observed. The PSA50 response was 50.0% (10/20), including 4 responders with visceral metastases, and confirmed PSA50 was 35.0% (7/20) in the PSA-evaluable population. With a median follow up of 2.7 months, median rPFS was still not reached (95% CI: 1.81, NE) with 68.2% (15/22) patients ongoing. ORR in the patients with measurable disease was 11.1% (1/9), with response at a site of liver metastasis. PK was linear with a mean half-life of 14 days. Biomarker assessment revealed an elevated on-treatment IL-6 level in a patient who had Grade 1 CRS. Increases in on-treatment IFN-γ and CD38+/CD8+ T-cells were observed following pasritamig treatment, indicating peripheral T-cell activation consistent with the proposed MOA. A higher baseline frequency of PD-1+/CD8+ T-cells was noted in PSA50 responders. Conclusions: The safety, efficacy, PK and PD profile of pasritamig in Asia is broadly consistent with the US & EU population reported previously. Longer follow up for efficacy and further quantification of responses in visceral lesions are in progress. These results highlight the potential of pasritamig to fulfill the unmet need for a safe T-cell based therapy for mCRPC and support the inclusion of Asian patients in global phase 3 trials. Clinical trial information: NCT04898634 .

<h3>Background and Importance</h3> Discrepancies between clinical remission and patients’ perceptions of their symptoms are common in psoriasis. While clinical scores such as PASI provide objective measures of disease activity, they may not fully capture the patient experience. Integrating patient-reported outcomes (PROs) is essential to complement clinical assessments and monitor treatment effectiveness. Adherence to biologic therapies is a key factor influencing long-term outcomes, yet its relationship with PROs remains underexplored in real-world settings. <h3>Aim and Objectives</h3> This study aimed to evaluate treatment adherence and explore its association with PROs in patients with moderate-to-severe psoriasis receiving guselkumab in routine clinical practice in Spain over a 12-month period. <h3>Material and Methods</h3> This was a prospective, observational, multicentre study including 269 adult patients across 39 Spanish dermatology centres. Baseline assessments included Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI). Adherence was measured using Medication Possession Ratio (MPR ≥90%) and the Morisky Medication Adherence Scale (MMAS-8 ≥6). PROs included the Treatment Satisfaction Questionnaire for Medication (TSQM), Hospital Anxiety and Depression Scale (HADS), and Psoriasis Signs and Symptoms Diary (PSSD). <h3>Results</h3> At baseline, mean age was 50.8 years, with a mean psoriasis duration of 16.5 years. Psoriatic arthritis was present in 35.3%, and 81.6% had prior biologic exposure. Mean PASI was 10.1, and DLQI was 9.8. At 12 months, 142 patients (52.8%) completed follow-up. Mean MPR was 96.7%, with 87.3% adherent by MPR and 96.5% by MMAS-8; 88.5% met both criteria. Concordance between MPR and MMAS-8 was low. At baseline, PROs were similar between adherent and non-adherent patients, except for HADS-anxiety (6.7 vs 10.4; p=0.007). At 12 months, trends favoured adherent patients in PSSD signs (21.1 vs 31.7; p=0.098) and HADS-anxiety (5.7 vs 7.9; p=0.076), though not statistically significant. <h3>Conclusion and Relevance</h3> High adherence to guselkumab was observed over 12 months. Preliminary findings suggest a potential association between adherence and improved patient-perceived outcomes, particularly anxiety and symptom burden. Combining objective and subjective adherence measures may enhance sensitivity in detecting these differences. These insights may inform strategies to optimise long-term psoriasis management. <h3>Conflict of Interest</h3> Corporate sponsored research or other substantive relationships: D. Martínez-López is an employee of Janssen-Cilag, the sponsor of this study. The remaining authors have no conflicts of interest to declare.

In dengue endemic, resource-limited settings, accurate and timely diagnosis is critical for effective clinical management and outbreak control, especially where multiple arboviruses co-circulate and overlap in clinical presentations. However, most dengue diagnosis in such settings rely on approaches with limited sensitivity such as clinical assessment, or easily deployable methods such as ELISA or rapid diagnostic tests (RDTs). Molecular diagnostics with superior diagnostic performance are rarely implemented beyond reference laboratories due to perceived logistical and operational barriers. This study provides real-world evidence comparing the performance of clinical, serological and molecular approaches for dengue diagnosis in a decentralized setting. We prospectively enrolled 271 patients with acute febrile illness at Santa Gema Hospital in Yurimaguas, Peru, during a dengue outbreak in 2023-2024. Patients underwent clinical evaluation (WHO 2009 dengue classification), and laboratory testing including NS1/ IgM RDTs and ELISAs, a triplex RT-PCR for ZIKV/DENV/CHIKV (ZDC-PCR), a newly developed multiplex RT-PCR for ZIKV/YFV/DENV/CHIKV (ZYDC-PCR), and a serotype-specific dengue RT-PCR used as reference. Diagnostic performance was assessed using sensitivity, specificity, ROC-AUC analysis, and logistic regression models. A subset of 131 samples underwent inter-laboratory comparison of the ZYDC-PCR between the regional (Yurimaguas) and central (Lima) laboratories. Of the 271 dengue-suspected cases, 88 (32.6%) were confirmed by the reference PCR. The ZYDC-PCR had a strong agreement with the reference (sensitivity 86.0%, Cohen's kappa 0.893) and consistent performance across the central and regional laboratory. NS1-based tests showed high specificity (≥96%) but moderate sensitivity (~72%). ROC analysis confirmed the accuracy of PCR (AUC = 0.97), outperforming RDTs, ELISAs (AUC = 0.85 to 0.89) and clinical assessment (AUC = 0.65). Our study demonstrates the added value and feasibility of implementing a multiplex PCR at a regional hospital to significantly improve diagnostic accuracy, enabling earlier detection of disease presence or absence, critical for clinical management and outbreak response.

Accurate quantification in LC–MS experiments becomes challenging when analytes overlap both chromatographically and in mass spectra, as conventional extracted ion chromatogram-based methods can yield biased results by double-counting shared isotope signals. This limitation is particularly relevant for oligonucleotides, where degradation products and synthetic impurities frequently co-elute with the intended full-length product, complicating relative quantification. To address this, we developed DECAF, a straightforward and computationally efficient procedure for deconvoluting overlapping isotope patterns directly from MS1 data. The method models experimental isotope distributions as mixtures of theoretical templates across retention time, generating deconvoluted ion chromatograms whose peak areas accurately reflect the contributions of individual components. We demonstrate the utility of DECAF on two pharmaceutically relevant oligonucleotide mixture datasets, where it reliably estimated mixing proportions and enabled visualisation of component-specific elution profiles. Analysis of a typical sample required one to two minutes, underscoring the method’s practical efficiency. DECAF provides a transparent and accessible alternative to existing commercial software, with promising applications in pharmaceutical analysis and quality control.

Abstract Background Shorter disease duration at biologic treatment initiation has been associated with improved therapeutic outcomes in Crohn’s disease (CD).1,2 Using pooled data from two randomized clinical trials, we evaluated whether disease duration impacts achievement of clinical and endoscopic outcomes in adults with active CD treated with guselkumab (GUS). Methods Post-hoc analyses used pooled data from the Phase 2/3 GALAXI 2 &amp; 3 studies in adults with moderately to severely active CD randomized to intravenous GUS 200mg at week (W) 0, W4, W8, followed by subcutaneous GUS 100mg every 8W (Q8W) from W16-40 or GUS 200mg Q4W from W12-44. Analyses were stratified by baseline (BL) disease duration: ultrashort (USDD; ≤1 year), intermediate-short (ISDD; &amp;gt;1 to ≤ 2 years), intermediate-long (ILDD; &amp;gt;2 to ≤ 5 years), and long (LDD; &amp;gt;5 years) disease duration. Rates for clinical response (100-point decrease from BL in CD Activity Index [CDAI] or CDAI&amp;lt;150), clinical remission (CDAI&amp;lt;150), endoscopic response (≥50% improvement from BL in Simple Endoscopic Score for CD [SES-CD] or SES-CD≤2), endoscopic remission (SES-CD≤4, ≥2-point reduction from BL in SES-CD, and no SES-CD sub-score &amp;gt;1), and deep remission (clinical and endoscopic remission) were evaluated at W12 (placebo-controlled period) and W48. Results Despite numerical differences, BL characteristics were generally balanced across disease duration subgroups; as expected, increasingly higher proportions of patients with a history of inadequate response or intolerance to biologic therapies were observed with longer disease duration (Table 1). At W12, GUS induction therapy was effective irrespective of disease duration (data not shown). Achievement rates in the pooled GUS groups increased through W48, with rates of clinical response (range: 74% to 78%), clinical remission (range: 65% to 73%), and endoscopic response (range: 47% to 54%) being comparable across disease duration subgroups. A clinically relevant trend toward lower rates of endoscopic remission (USDD: 44%; ISDD: 41%; ILDD: 35%; LDD: 31%) and deep remission (USDD: 43%; ISDD: 37%; ILDD: 29%; LDD: 28%) was observed with longer disease duration (Figure 1). Conclusion Among adults with moderately to severely active CD from GALAXI 2 &amp; 3, GUS demonstrated clinical and endoscopic benefits across disease duration subgroups with increasing rates through 1 year. A trend toward lower rates of endoscopic/deep remission at 1 year was observed in patients with longer disease duration, supporting earlier initiation of GUS treatment in the disease course.

Abstract Background Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23.1 The similar efficacy and safety of intravenous (IV) and subcutaneous (SC) induction with GUS in participants with moderately to severely active ulcerative colitis (UC) has been established in the phase 3 QUASAR and ASTRO studies.2,3 Obesity has the potential to impact the pharmacokinetic and pharmacodynamic parameters of subcutaneously administered medications. The aim of this post-hoc analysis was to determine whether body mass and body mass index (BMI) in participants with UC differentially affects the efficacy of GUS SC induction compared to IV induction. Methods Participants had moderately to severely active UC (modified Mayo score of 5-9, baseline Mayo rectal bleeding subscore ≥1, and Mayo endoscopic subscore ≥2) and a history of inadequate response/intolerance to oral corticosteroids, AZA/6-MP/MTX, biologics, Janus kinase inhibitors, and/or sphingosine-1-phosphate (S1P) inhibitors (ASTRO only). GUS phase 3 induction regimens were 200 mg IV in QUASAR (N = 421) or 400 mg SC in ASTRO (N = 279) at Weeks 0, 4, and 8, with matching placebo IV/SC (N = 280 and N = 139, respectively) as the comparator. Clinical response (decrease from baseline in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1) and clinical remission (stool frequency subscore of 0 or 1 and not increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0, or 1 with no friability present on the endoscopy) were evaluated at Week 12 across baseline weight quartiles and standard BMI subgroups (i.e., underweight [&amp;lt;18 kg/m2], healthy weight [≥18 to &amp;lt; 25 kg/m2], overweight [≥25 to &amp;lt; 30 kg/m2], and obese [≥30 kg/m2]). Weight quartiles and BMI subgroups were calculated for QUASAR and ASTRO separately. Results QUASAR and ASTRO had similar eligibility criteria, and the baseline demographics and disease characteristics of the randomized study populations were also similar (data not shown). Participants treated with GUS IV or SC induction achieved clinical response and clinical remission at Week 12 in similar proportions, with similar treatment effects compared to placebo, across all baseline weight quartile (Figure 1) and all baseline BMI (Figure 2) subgroups. Conclusion GUS IV and SC induction were similarly effective in participants with moderately to severely active UC compared with placebo regardless of participants’ baseline body weight or BMI. Obesity does not appear to diminish the efficacy of GUS SC induction.

Accurately measuring compound binding affinities is key to driving the pharmaceutical development process. Rigorous physics-based in silico approaches, particularly alchemical free energy methods, have become a gold standard tool for estimating compound affinity changes. Here we present the results of a large-scale pre-competitive collaborative assessment of relative binding free energy (RBFE) calculations generated by 15 pharmaceutical companies. We evaluate an open-source and MIT licensed RBFE Protocol from the Open Free Energy (OpenFE) ecosystem across both public and blinded private datasets, encompassing over 1,700 ligands in total. For the public dataset, the weighted RMSE across the 58 systems was 1.73 [1.53, 1.96] kcal/mol, with 10 of the systems reaching sub-kcal/mol accuracy. For the private dataset, the weighted RMSE across the 37 systems was 2.44 [1.94, 3.06] kcal/mol, with only 2 of the systems reaching sub-kcal/mol accuracy, reflecting the increased complexity of real-world drug discovery. The protocols performance was system-dependent, with no single dominant error source, indicating that accuracy is primarily influenced by input quality and transformation type. Overall, these benchmark results are encouraging and indicate that OpenFE is ready for large-scale industrial applications, with an "out-of-the-box" accuracy that approaches that of commercial solutions. While comparison against published FEP+ results, which were obtained after manual parameter optimization, shows comparable ranking statistics, a gap remains in error statistics, for which we outline possible paths toward improvement. The protocol meets key criteria required for production use in an industrial setting: it shows robust performance, generates reproducible results, and achieves both sufficient throughput and rapid convergence.

The development of 18F‐labelled radiotracers is of vital importance for (pre)clinical positron emission tomography (PET) imaging and to guide drug discovery campaigns. State‐of‐the‐art approaches often require labour‐intensive preparation of highly functionalised radiolabelling precursors. This bottleneck impedes analogue generation for optimal imaging and exploration of radiochemical space. To this end, we disclose a nickel‐mediated aryl (C)sp2‐(C)sp3 cross‐coupling with amine‐derived alkyl 2,4,6‐triphenylpyridinium salts as coupling partners amenable to radiosynthesis. The method was applied to primary and secondary 2,4,6‐triphenylpyridinium salts in radiochemical conversion (RCC) up to 86% and a high‐throughput experimentation (HTE) assay proved crucial for expedient ligand evaluation. A late‐stage diversification case study from a sole precursor achieved six 18F‐labelled GSK‐3 kinase inhibitor analogues, one being prepared in up to gigabecquerel (GBq) quantities in a (semi)automated two‐step protocol applied across three commercial radiosynthesis platforms.