Matthias Machacek | Managing Director
LYO-X AG

Matthias Machacek holds an engineering MS/PhD from ETH Zurich and completed his postdoctoral research in Cell Biology at The Scripps Research Institute. He brings more than 30 years of experience in modeling and simulation, supporting the preclinical and clinical development of biologics and other advanced drug modalities. During his time at Novartis, he established and led the group that helped lay the foundations for what is now known as Quantitative Systems Pharmacology (QSP). He is currently Managing Director of LYO-X, a PK/PD and QSP modeling company he founded in 2024.

Appearances:

Festival of Biologics Day 1 @ 13:30

First in Human Dose Selection for ADCs and TCEs Using PK/PD and QSP

First-in-human dose selection remains one of the highest-stakes decisions in oncology drug development—particularly for complex modalities such as Antibody-Drug Conjugates (ADCs) and T-cell Engagers (TCEs). Misjudging this step can lead to delayed development, unnecessary patient risk, and significant value loss.

In this workshop, LYO-X presents an integrated, model-informed strategy to de-risk and accelerate FIH dose prediction. For ADCs, the focus is on translating preclinical data into a robust understanding of therapeutic dose and window. For TCEs, the challenge lies in identifying a starting dose that is both safe and sufficiently close to pharmacological activity, minimizing dose-escalation steps and avoiding subtherapeutic exposure.

By combining in vitro and in vivo preclinical data with advanced PK/PD and quantitative systems pharmacology (QSP) modelling, LYO-X demonstrates how to generate data-driven, decision-ready dose recommendations. The session will highlight how this approach enables more confident clinical entry, optimizes trial design, and ultimately accelerates time to proof-of-concept.

Matthias Machacek, Managing Director, LYO-X AG

Alejandro Sanz Garcia, PKPD modeler, LYO-X AG