Part 2 of this blog series dives further into the June 2022 podcast with R&D World editors, Paul Heney and Aimee Kalnoskas, having their minds blown — multiple times! — which explores Certara’s Simcyp COVID-19 Vaccine Model, a 2021 R&D 100 Awards winner, revealing the genesis of the model, as well as some stunning possible future uses for it. Read Part 1 of the blog series here.
QSP for New Horizons
By providing integrated approaches to assessing new drug modalities and mechanisms of action, QSP can be applied very early in the evaluative process to determine the first dose and understand potential toxicity issues along with longer-term therapeutic value. At Certara, we have been applying QSP to understand the potential for a range of new modalities, including:
- Genetic therapies, including AAV, lysosomal storage disease, glycogen storage disorder, enzyme replacement, and genetically engineered antibodies. For an example, read this blog on dose optimization using the Gene Therapy Virtual Twin Platform.
- Protein degradation. By harnessing the body’s own natural protein disposal system to degrade and remove disease-causing proteins, this approach is being leveraged to identify new drug targets.
- mRNA and traditional vaccines. Note this recent interview of Andrzej Kierzek and myself in Nature magazine, where we addressed how the QSP model allowed for optimized dosing intervals.
- Bi, tri and multi-specifics. Bispecific and trispecific antibodies are essentially antibodies bioengineered to contain two or three distinct antigen-binding domains, which allow these recombinant molecules to bind specifically to more than one target. QSP enables the in silico biological exploration of these complexities to achieve desired therapeutic response.
- Microglia and neuroinflammation. Microglia, as the immune cells in the CNS, play crucial roles in neuroinflammation and many other CNS diseases. QSP is being applied to understanding the dynamics of microglial phenotypes and effects on treatments targeting microglia, as shown in this recent scientific poster.
- CAR-T – read more about our collaboration with the Memorial Sloan Kettering Cancer Center. This new biosimulation platform initially aims to address key questions on the optimal dose and regimen for CAR T-cell therapies in patients with multiple myeloma and will leverage de-identified MSK clinical data. Certara hopes to expand the use of the CAR T-cell biosimulation platform to evaluate combination therapies and enhance the manufacturing learning process for next generation CAR T-cell therapies.
- Gene Editing. This Nobel Prize winning technology approach allows genetic material to be added, removed, or altered at particular locations in the genome. Certara is using its QSP platforms to guide dose selection and decision-making across several different types of gene editing, including CRISPR/CAS9 and base editing.
From Early Development to Regulatory Submission
Once considered a technology for the pre-clinical to translational space, QSP’s benefits and uses have since expanded into later stage clinical through to NDA/BLA approval. Increasingly, our team is working on QSP models that align to biomarkers that predict clinical endpoints, even in new areas such as connecting tissue biomarker predictions to clinical scoring systems. An exciting development is our novel approach to predict clinical outcomes for novel treatments in irritable bowel disease (IBD) using virtual populations, which will be presented at the upcoming American Conference on Pharmacometrics (ACoP) meeting.
QSP at Certara is always ready to take the next R&D step and continue to blow minds.