Modular Therapeutics

Modular Therapeutics is a spinoff biotechnology company from the Netherlands Cancer Institute (NKI) founded to translate the RNA dicing model into next-generation precision therapeutics. The company builds directly on discoveries originating from our academic research, which revealed that many genes do not function as single, monolithic units but instead produce multiple internal mRNA isoforms with distinct - and sometimes opposing - biological activities.

By leveraging RNA dicing, Modular Therapeutics develops technologies for isoform-resolved drug design, patient stratification, and drug repurposing, addressing key limitations of current pharmacological approaches that overlook internal gene complexity. This high-resolution view of gene expression enables more accurate prediction of drug efficacy, reduced toxicity, and improved clinical outcomes.

Modular Therapeutics operates at the interface of molecular biology, bioinformatics, transcriptomics, and proteomics, and collaborates closely with academic labs and clinical partners. Its long-term vision is to establish RNA dicing as a foundational platform for isoform-specific therapeutics across cancer and other complex diseases.

JAK1 Project - Isoform-Resolved Precision Oncology

The JAK1 project is the lead translational program at Modular Therapeutics and a proof-of-concept for RNA dicing-based drug development.

Using the RNA dicing model, we identified that JAK1 produces distinct internal isoforms with opposing biological functions. While the canonical full-length JAK1 isoform exhibits tumor-suppressive activity, RNA dicing generates a truncated kinase isoform with oncogenic properties. These isoforms cannot be resolved by conventional genomic or transcriptomic analyses.

This framework redefines the functional impact of JAK1 frameshift and nonsense mutations, which selectively impair the tumor-suppressive isoform while preserving or enhancing the oncogenic diced isoform. As a result, tumors carrying these mutations display aggressive behavior.

Importantly, we show that JAK1-mutant tumors exhibit increased sensitivity to specific JAK1 inhibitors at lower doses, enabling accurate patient stratification, drug repurposing, and reduced toxicity through isoform-aware targeting. This project provides a foundation for extending RNA dicing-driven therapeutic strategies to additional cancer-relevant genes.

IsoFrame - A Dynamic Model for Intra-Gene Expression Analysis

IsoFrame is a computational and conceptual framework developed to resolve gene expression at the level of intra-gene isoform architecture, rather than treating genes as single, monolithic units.

Conventional genomics, transcriptomics, and proteomics approaches primarily quantify total gene expression, overlooking the fact that a single gene can produce multiple internal RNA and protein isoforms with distinct - and sometimes opposing - biological functions. IsoFrame is built on the RNA dicing model and captures this dynamic, modular expression reality, enabling high-resolution analysis of canonical and truncated isoforms across biological conditions.

By integrating RNA sequencing, proteomics, and additional omics layers, IsoFrame reconstructs isoform-specific expression signatures that reflect translational potential, domain composition, and predicted drug responsiveness. This approach provides mechanistic insight into processes such as patient stratification, drug sensitivity, drug resistance, and tumor plasticity, which are poorly explained by bulk expression analyses.

IsoFrame has been applied across multiple disease contexts, including cancer, immune activation, and drug-treated patient-derived models, revealing isoform dynamics that are invisible to standard differential expression tools. These insights form the basis for isoform-aware therapeutic strategies, biomarker discovery, and the development of machine-learning models for precision medicine.

Patents

Malka, Y., Faller, W.J. Janus kinase (JAK) inhibitors for treating cancer. Application number PCT/NL2025/050071.

Malka, Y. RNA Dicing-Based Discovery and Computational Framework for Isoform-Specific Therapeutics and Stratification. Application number 1045163

Malka, Y. Comprehensive Therapeutic and Diagnostic Applications of RNA Dicing Modulation and Isoform-Specific Targeting Across Disease Pathologies. Application number 1045164