Cellworks Biosimulation Predicts Chemotherapy Benefit in EGFR-mutated NSCLC Patients on Osimertinib

Cellworks Group Inc., an innovator in Personalized Therapy Decision Support and Precision Drug Development, recently published findings from a study utilizing its platform to assess the advantages of integrating chemotherapy with osimertinib therapy for patients with EGFR-mutated non-small cell lung cancer (NSCLC). The study utilized data from a real-world retrospective cohort and employed biosimulation techniques to predict treatment outcomes. It demonstrated that combining chemotherapy with osimertinib resulted in a higher predicted overall response rate (ORR). However, the benefits varied across patients based on their genomic profiles, allowing for the identification of individuals who would benefit most from combined therapies versus those who might achieve similar outcomes with osimertinib alone.

The results of this study were presented at the IASLC 2024 World Conference on Lung Cancer in San Diego, California.

Dr. Charu Aggarwal from the University of Pennsylvania, the study's principal investigator, explained that while osimertinib has become a standard treatment for NSCLC patients with EGFR mutations, there were uncertainties regarding the added benefits of chemotherapy for some patients. The Cellworks biosimulation platform provided valuable insights, enabling a more precise prediction of chemotherapy benefits by analyzing individual mutation profiles.

Dr. Michael Castro, Chief Medical Officer of Cellworks, emphasized that the study offers new directions for optimizing treatment strategies in NSCLC patients with EGFR mutations. By identifying additional biomarkers influencing chemotherapy responses, the research contributes to a better understanding of patient-specific disease profiles and their impacts on therapy effectiveness. According to Dr. Castro, EGFR blockade can counteract chemotherapy resistance in some patients by downregulating mechanisms that inhibit apoptosis and DNA repair, thereby enhancing the effectiveness of combined therapy.

The study employed Cellworks' computational biosimulation to assess the additive value of chemotherapy in advanced NSCLC patients with EGFR mutations. It analyzed a retrospective cohort of 116 frontline NSCLC patients treated with osimertinib from the Flatiron Health-Foundation Medicine NSCLC clinico-genomic database. Biosimulated efficacy scores were generated for treatment with osimertinib alone and in combination with carboplatin and pemetrexed. The study evaluated improvements in predicted clinical response by comparing efficacy scores, using the upper 95% confidence interval of the osimertinib efficacy score as a benchmark.

The study showed that osimertinib efficacy scores were significantly associated with clinical outcomes, validating the predictive capability of Cellworks' biosimulation. Adding chemotherapy to osimertinib increased efficacy scores for some patients, allowing for more precise treatment selection. This approach moves beyond generalizations, recognizing that chemotherapy benefits are not uniformly distributed across all patients. Biosimulation aids in identifying patients who are likely to benefit most from combination therapy compared to sequential treatment.

The Cellworks Platform uses multi-omic data from patients to simulate the effects of specific drug combinations on individual disease profiles. This is achieved through the Computational Biology Model (CBM), a detailed network of human genes, molecular species, and interactions. This model, combined with relevant drug models, predicts therapy responses and generates a qualitative Therapy Response Index (TRI) score for specific treatments. The Cellworks CBM has been validated through numerous clinical datasets, presentations, and publications.

Cellworks Group Inc. is at the forefront of Personalized Therapy Decision Support and Precision Drug Development. The company's platform leverages computational biology and biosimulation technology to predict therapy responses for individual patients and cohorts. Based in South San Francisco, with facilities in Tennessee and India, Cellworks is backed by several venture capital firms and collaborates globally to improve patient outcomes.