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Transforming commercial pharma with agentic AI
Amid the turbulence of the wider global economy in recent years, the pharmaceuticals industry is weathering its own storms. The rising cost of raw materials and supply chain disruptions are squeezing margins as pharma companies face intense pressure—including from countries like the US—to control drug costs. At the same time, a wave of expiring patents threatens around $300 billion in potential lost sales by 2030. As companies lose the exclusive right to sell the drugs they have developed, competitors can enter the market with generic and biosimilar lower-cost alternatives, leading to a sharp decline in branded drug sales—a “patent cliff.” Simultaneously, the cost of bringing new drugs to market is climbing. McKinsey estimates cost per launch is growing 8% each year, reaching $4 billion in 2022.

In clinics and health-care facilities, norms and expectations are evolving, too. Patients and health-care providers are seeking more personalized services, leading to greater demand for precision drugs and targeted therapies. While proving effective for patients, the complexity of formulating and producing these drugs makes them expensive and restricts their sale to a smaller customer base.

The need for personalization extends to sales and marketing operations too as pharma companies are increasingly needing to compete for the attention of health-care professionals (HCPs). Estimates suggest that biopharmas were able to reach 45% of HCPs in 2024, down from 60% in 2022. Personalization, real-time communication channels, and relevant content offer a way of building trust and reaching HCPs in an increasingly competitive market. But with ever-growing volumes of content requiring medical, legal, and regulatory (MLR) review, companies are struggling to keep up, leading to potential delays and missed opportunities.
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Nature, Published online: 07 October 2025; doi:10.1038/d41586-025-03287-y
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ABSTRACT
Genetics and pathobiology were addressed at the 7th World Symposium on Pulmonary Hypertension in Task Forces 2 and 3. The Genetics Task Force also focused on precision medicine approaches, and the Pathobiology working group concentrated heavily on new omics technologies. Therefore, the following not only summarises the current state of knowledge on genetics, genetic testing methods, and molecular pathophysiological changes, but also places it in context and critically discusses it. In addition, the importance of national and international biobanks and cohorts, as well as the active involvement of patients and families, is emphasized.
PMID:41052524 | DOI:10.1055/a-2625-4648
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Nature Medicine, Published online: 06 October 2025; doi:10.1038/s41591-025-03983-2
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Front Immunol. 2025 Sep 19;16:1631708. doi: 10.3389/fimmu.2025.1631708. eCollection 2025.
ABSTRACT
This study investigates the role of ubiquitination-related genes in pancreatic cancer (PC) using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and multi-omics approaches. scRNA-seq data (GSE155698) from PC samples identified 12 cell types, with endothelial cells exhibiting high ubiquitination scores (High_ubiquitin-Endo) and enriched interactions with fibroblasts/macrophages via WNT, NOTCH, and integrin pathways. Spatial transcriptomics (GSE235315) validated cell-type localization. Mendelian randomization (SMR) analysis prioritized TRIM9 as a PC-protective gene, downregulated in tumors and correlated with better survival. WGCNA revealed TRIM9-co-expressed modules linked to prognosis. A machine learning-based prognostic model (CoxBoost+RSF) integrating seven genes (TSPAN6, TSC1, RNF167, PBXIP1, LRRC49, KATNAL2, IGF2BP2) stratified patients into high/low-risk groups with distinct survival, mutation burdens, and immune infiltration. TRIM9 overexpression suppressed PC cell proliferation/migration in vitro, while knockdown enhanced malignancy. Mechanistically, TRIM9 promoted K11-linked ubiquitination and proteasomal degradation of HNRNPU, dependent on its RING domain. In vivo, TRIM9 overexpression reduced tumor growth, rescued by HNRNPU co-expression. Integrated analyses highlight TRIM9 as a tumor suppressor and prognostic biomarker, mediated via ubiquitination-dependent regulation of HNRNPU stability. This work provides insights into ubiquitination-driven PC pathogenesis and therapeutic targeting.
PMID:41050689 | PMC:PMC12491318 | DOI:10.3389/fimmu.2025.1631708
A computational medicine framework integrating multi-omics, systems biology, and artificial neural networks for Alzheimer's disease therapeutic discovery
Acta Pharm Sin B. 2025 Sep;15(9):4411-4426. doi: 10.1016/j.apsb.2025.07.018. Epub 2025 Jul 16.
ABSTRACT
The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.
PMID:41049755 | PMC:PMC12491700 | DOI:10.1016/j.apsb.2025.07.018
MOFNet: a deep learning framework for multi-omics data fusion in cancer subtype classification
Mol Omics. 2025 Oct 1. doi: 10.1039/d5mo00221d. Online ahead of print.
ABSTRACT
BACKGROUND: cancer exhibits high molecular and clinical heterogeneity, making accurate subtyping essential for personalized treatment. Traditional single-omics approaches often fail to capture this complexity. Multi-omics integration offers a more holistic understanding, but many existing methods either lack interpretability or fail to model cross-omics correlations effectively.
METHODS: we developed MOFNet, a novel supervised deep learning framework for multi-omics integration, incorporating a similarity graph pooling (SGO) module and a view correlation discovery network (VCDN). MOFNet processes omics data-including mRNA expression, DNA methylation, and miRNA expression-via omics-specific graph learning and cross-omics label space fusion. Three cancer types-breast cancer (BRCA), low-grade glioma (LGG), and stomach adenocarcinoma (STAD)-were analyzed using datasets from the cancer genome atlas (TCGA). Statistical evaluation was performed using accuracy, weighted F1 score, and macro F1 score across stratified training/testing splits.
RESULTS: MOFNet achieved superior performance across all datasets. For BRCA, it obtained an accuracy of 85.17%, F1_weighted of 85.36%, and macro F1 of 80.93%, outperforming all baseline models by up to 18.25%. In LGG and STAD, MOFNet also showed robust gains, with maximum improvements of 23.72% and 21.56%, respectively. Omics ablation studies demonstrated enhanced performance with multi-omics integration. Functional enrichment analysis revealed that MOFNet-identified key features were involved in biologically relevant pathways such as cell cycle regulation, synaptic signaling, and ion transport.
CONCLUSIONS: MOFNet enables scalable and interpretable multi-omics data fusion for cancer subtype classification, significantly improving predictive accuracy while retaining only 25% of input features. The integration of SGO and VCDN modules offers both biological interpretability and computational efficiency. These results suggest MOFNet's promising application in precision oncology and biomarker discovery.
PMID:41031935 | DOI:10.1039/d5mo00221d
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Nat Rev Clin Oncol. 2025 Oct 3. doi: 10.1038/s41571-025-01077-z. Online ahead of print.
ABSTRACT
Patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) predominantly receive chemotherapy, and despite initial responses in some patients, most will have disease progression and often dismal outcomes. This lack of clinical effectiveness partly reflects not only cancer cell-intrinsic factors but also the presence of a tumour microenvironment (TME) that precludes access of both systemic therapies and circulating immune cells to the primary tumour, as well as supporting the growth of PDAC cells. Combined with improved preclinical models of PDAC, advances in single-cell spatial multi-omics and machine learning-based models have provided novel methods of untangling the complexities of the TME. In this Review, we focus on the desmoplastic stroma and both the intratumoural and intertumoural heterogeneity of PDAC, with an emphasis on cancer-associated fibroblasts and their surrounding immune cell niches. We describe new approaches in converting the immunologically 'cold' PDAC TME into a 'hot' TME by priming T cell activation, overcoming T cell exhaustion and unravelling myeloid cell-mediated immunosuppression. Furthermore, we explore integrated targets involving the TME, such as points of convergence among tumour, stromal and immune cell metabolism as well as oncogenic KRAS signalling. Finally, building on our experience with failed clinical trials in the past, we consider how this evolving comprehensive understanding of the TME will ensure future success in developing more effective therapies for patients with PDAC.
PMID:41044427 | DOI:10.1038/s41571-025-01077-z