Inspire

Decentralized clinical trials offer a scalable approach to evaluate patient research in real-world settings. The COSMOS–DIGITAL study ([NCT06761703][1]) was designed to assess the feasibility of recruiting patients using antiobesity medications from an online patient community and aimed to evaluate participants' willingness to consent to and complete fully decentralized surveys and at-home self-blood testing. Three-quarters (n = 151; 75.5%) of participants completed all self-collected capillary blood samples, Patient-Reported Outcomes in Obesity (PROS) surveys, and nausea-related surveys. Over 83% of participants completed the surveys (PROS: n = 167; 83.5%; daily nausea: n = 168; 84.0%), and 93% (n = 142/152) of collected blood samples were sufficient or partially sufficient for testing. Overall, participants were satisfied with the at-home blood collection device. Digitally enabled, fully decentralized studies can capture blood samples and survey responses as well as important aspects of patient treatment experiences, adding value to data collected in randomized controlled trials. ### Competing Interest Statement BK, SS, JMC, HK, and PB are employees of Amgen Inc., and own stock. MC is a former employee of Amgen Inc. and owns stock. MM is an employee of YourBio Health, Inc. BC has no competing interests. ### Clinical Trial NCT06761703 ### Funding Statement This study was funded by Amgen, Inc. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The IRB of Advarra (Columbia, MD, USA) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Qualified researchers may request data from Amgen clinical studies. Complete details are available at https://www.amgen.com/science/clinical-trials/clinical-data-transparency-practices/clinical-trial-data-sharing-request. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT06761703&atom=%2Fmedrxiv%2Fearly%2F2026%2F01%2F28%2F2026.01.26.26344623.atom

Nanofillers play a crucial role in designing high-strength polymer materials but contribute less to extensibility and often complicate processing. This paper presents a new strategy for developing polymer composites with outstanding tensile strength, extensibility, and processability, driven by the slip-transfer effect of cation-pi interactions between nanofillers and polymer chains. These composites belong to a class of fusible, stiff polymers with excellent mechanical properties. The indole groups on the polymer chains can slip over the K+-functionalized fillers due to dynamic interactions, characterized by the continuous dissociation and reconstruction of cation-pi interactions between the indole groups and K+ under an external force. This mechanism imparts exceptional extensibility to the polymer composites. Additionally, the slip-transfer effect enhances the processability of these composites.

BACKGROUND:Patients with short bowel syndrome-associated intestinal failure (SBS-IF) require complex, personalized, and multidisciplinary care; however, there are disparities in access. This study measured the impact of unmet needs and treatment burden among patients and their caregivers. METHODS:This cross-sectional, mixed-method study included US adults self-reporting SBS-IF and receiving home parenteral nutrition for ≥6 months and their caregivers. One-hour interviews informed the development of a 30-min survey administered to participants from an online health community. RESULTS:Among 68 patients, the mean age was 42 years, 79% were female, and 88% were White. Most of the 16 caregivers were female (69%), and younger than 45 years (69%). Of 32 patients (47%) receiving care from an SBS specialist, only 19 (59%) were referred after diagnosis; in 58% of these, referral occurred >6 months after diagnosis. Depression was reported in 44 patients (65%), with 54% not receiving professional mental health care. Financial concerns were common, with 44 patients (65%) unable to work and 40 patients (59%) reporting annual household income of <$50,000. Of 32 patients reporting difficulty paying medical bills, 22 (32%) could not fill prescriptions and 19 (28%) canceled/delayed healthcare provider visits. Social determinant of health challenges were reported by 44 patients (65%). Caregivers' responsibilities impacted their ability to work (50%) and future outlook (63%). CONCLUSION:Patients with SBS-IF face difficulties accessing specialized healthcare, and are at risk of adverse healthcare outcomes, financial hardships, and poor quality of life. Mental health and work/financial issues were common among both patients and caregivers.

Development of new therapies relies on rigorous testing in physiologically relevant, predictive in vitro models. This approach reduces the attrition of preclinical candidates going into animal studies and onto Phase 1 trials. While 2D tumor cell cultures have traditionally been the norm in early drug screening due to their automation compatibility and ease of use, they are no longer the optimal choice for drug development. This is due to their lack in translatability to human physiology, which is essential for assessing aspects of the cellular microenvironment, intercellular interactions, and the role of immune cells. The generation of 3D in vitro tumor spheroids for high-throughput screening campaigns can be labor-intensive, particularly at the lead discovery stage. The availability of a constant, reproducible supply of a panel of tumor spheroids for target ID and target validation studies represents a significant time and resource saving. To provide more flexibility in large-scale screening for therapeutic candidates in oncology, we developed a new platform offering a wide range of cryopreserved 3D tumor models in microplate format, enabling off-the-shelf high-content screening. The platform allows users to begin testing compounds within 3-5 days by just thawing an ARCTis™ plate (Always Ready Cryo Tissues) and following a few instructions. Another advantage of these cryopreserved 3D models is that they are manufactured in larger batches under highly standardized processes, ensuring a consistent starting point for compound testing. This results in enhanced data quality, an extended test window length, and data that is comparable across workgroups. Our current portfolio comprises 20 tumor cell lines from ATCC, representing the most common solid tumors. Staurosporine has been used as a positive control to detect a dose-dependent effect on cell viability. Following this treatment the dose-response indicated growth inhibition, shrinkage or tumor cell killing effects based on size and metabolic analysis (ATP). Furthermore, we demonstrated the robust performance of these assays for plates stored up to 6 months at -80 °C. This study demonstrates the efficacy of selected small molecules to show the functionality of the spheroids and to compare their functionality across different tumor models. Therefore, we will present applications for ARCTis™ plates that proof their relevance for pre-clinical testing. In conclusion, this innovative approach addresses the limitations of traditional 2D cell cultures by providing a high-throughput, in-plate frozen, 3D cell culture platform and access to a large tumor panel for parallel testing, offering a more physiologically relevant representation of tumor diversity. Our robust frozen flexible assay platform offers a promising new approach to advancing cancer drug discovery, streamlining the exploration of complex drug testing screens in vitro. Madhu Nag, Simon Ströbel, Simon Hutter, Tala Issa, Laure-Anne Ligeon, Nils Goedecke, Olivier Frey. Cryopreserved 3D human tumor spheroid platform in 96-well format for robust & scalable discovery and screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1220.

The advancements in biotechnology and the successful application of monoclonal antibody therapeutics have incited the development of innovative therapeutic antibody modalities, including bi-or tri-specific antibodies, antibody fragments (e.g. Fab), and other formats (e.g. DARPin). These have transformed cancer treatments; however, monoclonal antibodies often demonstrate limited efficacy in cancer therapy due to poor tumor penetration, leaving regions of untargeted and untreated tumor areas that can escape therapy. Addressing this limitation requires the development of advanced in vitro culture models that accurately replicate tumor-tumor microenvironment (TME) interactions. To bridge the gap between traditional 2D in vitro cultures and animal models, 3D human tumor spheroids offer a promising solution. In this context, InSphero has developed an in vitro 3D Antibody Penetration Assay. We demonstrate that 3D InSight™ Human Tumor Microtissues closely mimic the complexity and heterogeneity of the TME, while maintaining uniform composition and size across spheroids, providing reliable and reproducible models to enhance drug discovery. Using 3D InSight™ human tumor spheroids, we evaluated the efficacy, distribution, and penetration depth of a therapeutic antibody and an antibody-drug conjugate (ADC). Results showed that both modalities successfully penetrated the 3D InSight™ lung cancer tumor (A549) model. After 30 minutes of treatment, antibodies were detected at the periphery of the spheroids, while longer treatment windows resulted in progressively deeper penetration. This assay offers a robust and reliable platform for assessing the distribution and penetration of antibody therapeutics, biologics, ADCs, and other agents in solid tumor models, leveraging advanced in vitro 3D human tumor models to improve drug discovery and therapeutic development. Sue Fontaine Grepper, Maja Nedic, Charlotte Veser, Michal Rudnik, Matthias Zbinden, Irina Agarkova, Madhu Nag, Laure-Anne Ligeon. Advancing antibody therapeutics: a 3D in vitro model for penetration assessment of immunoglobulins in human tumor spheroids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3464.