Certara & Ichnos Glenmark Collaboration Optimizes Dosing for Potential First-In-Class Cancer Drug

Certara, Inc., a prominent player in model-informed drug development, recently shared promising results from its partnership with Ichnos Glenmark Innovation (IGI) concerning the initial dose prediction and selection for the trispecific T-cell engager (TCE), ISB 2001. The drug candidate, seen as a potential cancer therapy, has shown significant potential in preclinical studies. These findings were documented in the journal Nature Cancer, emphasizing ISB 2001’s therapeutic promise for patients with relapsed or refractory multiple myeloma.

Traditionally, the translation of data from animal models to human patients poses significant challenges, often necessitating a conservative approach to first-in-human (FIH) dose selection. To address this, IGI collaborated with Certara to refine the FIH dose of ISB 2001, aiming to balance patient safety with efficacy. Certara utilized its innovative virtual clinical trial platform, integrating expertise in quantitative systems pharmacology (QSP) and physiologically-based pharmacokinetics (PBPK).

Piet van der Graaf, PharmD, Ph.D., Senior Vice President and Head of Applied Biosimulation at Certara, expressed pride in the collaborative effort. He highlighted the comprehensive biosimulation strategy employed, which allowed for effective virtual trials of ISB 2001. According to van der Graaf, the application of virtual patient technology is instrumental in optimizing human dosing and accelerating the drug's journey to patients.

The collaboration led to a significant increase in the clinical starting dose, estimated to be 50-100 times higher than the conventional approach. This adjustment aims to minimize the risk of administering ineffective doses to cancer patients. The U.S. FDA and Australian HREC have accepted this innovative method, which could set a precedent for determining FIH dosing for ISB 2001 and similar TCEs.

Moreover, the use of virtual trials to optimize ISB 2001 dosing provides notable time and cost efficiencies. In an industry under constant pressure to expedite drug delivery to patients, such efficiency is crucial. An optimized dose strategy reduces the time spent on dosing patient cohorts with sub-therapeutic levels, aligning with regulatory goals in the U.S. and Europe, including the FDA Modernization Act 2.0. This approach also reduces the reliance on animal studies, supporting more ethical research practices.

Mario Perro, Ph.D., Head of Biologics Research at IGI, emphasized the importance of the collaboration with Certara for ISB 2001’s success. Utilizing the adapted QSP model, the team could predict a first-in-human dose with an acceptable safety margin, reducing the number of patients exposed to sub-therapeutic doses.

Certara's role in this research underscores its mission to accelerate drug development using biosimulation software, technology, and services. The company collaborates with over 2,400 biopharmaceutical firms, academic institutions, and regulatory agencies worldwide, pushing the boundaries of traditional drug discovery and development.

The collaborative effort between Certara and IGI marks a significant milestone in the optimization of cancer treatment dosing, showcasing the potential of virtual trials and biosimulation in modern medicine.