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令人惊叹的 QSP 在药物开发中的应用:Part 2

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.

关于作者

Piet van der Graaf, PharmD, PhD
By: Piet van der Graaf, PharmD, PhD

Piet van der Graaf 现任 Certara 高级副总裁兼 QSP 负责人,同时也是莱顿大学系统药理学教授。Piet 是 2013 - 2016 年莱顿药物研究学术中心的研究主任。1999 - 2013 年,Piet 在辉瑞公司的研发生物学、药代动力学和药物代谢、以及临床药理学等部门担任过多种领导职务。Piet 于2012 - 2018 年担任 CPT: Pharmacometrics & Systems Pharmacology 的创始主编,随后成为 Clinical Pharmacology& Therapeutics 的主编。Piet 曾在伦敦国王学院师从诺贝尔奖获得者 Sir James Black,接受了临床医学的博士培训。他曾获得 2024 年美国临床药理学与治疗学会(ASCPT)颁发的 Gary Neil 药物开发创新奖,同时也是国际定量药理学会(ISoP)2021 年领袖奖的获得者。Piet 是英国药理学会的当选委员,在定量药理学和药物开发领域发表了超过 200 篇同行评议的论文。

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