About the workshop

Model-informed approach for safe starting dose estimation in First-in-Human trials 

Dates:

2 June 2025

9:00-17:00, lunch 13:00-14:00 (7 hours)

Target audience:

Pharmacometricians, modeling scientists and students who seek to gain in-depth knowledge of bispecific antibody drug development, with emphasis on pharmacokinetics, pharmacodynamics and practical skills in quantitative systems pharmacology modeling

Mentors:

Victoria Kulesh, Dr. Victor Sokolov, Dr. Alina Volkova, Dr. Yuri Kosinky, Dr. Kirill Peskov

Pricing and format:

500 (250*) EUR for industry excl. VAT

250 (100*) EUR for academics excl. VAT

150 (free of charge*) EUR for academics excl. VAT

* for online participation

25 offline seats + 25 online seats

Annotation:

Join us for a one-day workshop hosted by M&S Decisions, to focus on translational mechanistic modeling in support of First-in-Human (FiH) safe starting dose selection.

The topic addressed in the workshop is of utmost importance, given the intricacies in pharmacokinetics and pharmacodynamics, and the corresponding unique safety challenges inherent to this multi-component therapeutic modality. The mechanistic modeling approach presented, which we will examine in a practical, hands-on manner, represents a must-have element in CTA/IND submissions.

The case examples which we will be focusing on during the workshop are based on the actual modeling applications in the development of T cell engagers (TCE) and other types of bispecific antibodies, although the overall methodology becomes generally for other types of novel multi-component therapeutics, such as autologous and allogenic cell therapies, antibody-drug and -oligo conjugates, targeted lipid or polymer nanoparticles with encapsulated drug, PROTACs etc.   

In fact, our session will take participants through various modeling approaches, from a more empirically driven workflow to estimate FiH starting dose using minimal anticipated biological effect level (MABEL) criteria, to a mechanistically oriented translational approach using a quantitative systems pharmacology (QSP) modeling workflow The latter will be based on an integrative cloud infrastructure, “Simurg”, and a set of packages from the R programming environment.

The workshop covers the following key elements of FiH dose selection for bispecific antibodies:

• Therapeutic utility and challenges in the development of complex, multi-component biologics and cellular therapies;
• Implementation of FiH dose selection based on MABEL criteria;
• Model-based analysis of in vitro cytotoxicity data, while accommodating for diverse experimental conditions (incubation time, E:T ratio, various cell lines, etc.) using fitting algorithms implemented in NONMEM, Monolix, nlmixr and Simurg;
• Development of a translational QSP model to predict exposure-efficacy and exposure-safety relationships in patients – from exploratory data analysis to advanced diagnostics;
• Generation of virtual patient populations which take into account variabilities in PK and in diverse disease states and immunological conditions;
• Implementation of model-informed selection of pharmacologically active and safe starting doses for bispecific antibodies, based on a case study with TCE;
• Regulatory requirements for inclusion of the MIDD approaches to support CTA/IND applications.

Technical requirements:

Laptop and functional browser.

For details: The program – M&S