The event on May 8th featured distinguished speakers from the industry, Dr. Frank Gibbons of AstraZeneca and Dr. Dean Bottino of Takeda. They showcased novel quantitative and systems pharmacology (QSP) applications in oncology. The master of ceremony was Chidera Anugwom, Boston QSP. The event was chaired by Dr. Birgit Schoeberl, former Head of Discovery and Sr. VP, Merrimack Pharmaceuticals.
Dr. Dean Bottino began by making a powerful analogy between oncology drug development and rocket science by asking a question “What if we did the 1969 “Moonshot” the way we develop cancer drugs today?” The analogy was apt given the Cancer Moonshot initiative. Rather than running a series of expensive experiments increasing the fuel level until a maximum tolerance is reached, engineers used different disciplines of science and mathematics to optimize fuel level and overall mission development and execution. Dr. Bottino argued for a similar approach to be taken in oncology; for example, using various mathematical modeling and simulation (M&S) approaches to make predictions for toxicity rather than conducting expensive, risky, and time consuming experiments by dosing incrementally until finding the toxicity level.
Dr. Bottino’s discussed three examples of model based oncology. In his first example, dose-exposure models were built to test efficacy of Alisertib when treating tumors. His second example explored combinations of novel-novel drugs. The combinations of different amounts of the two drugs formed an “efficacy surface” in a 3 dimensional space that was used to identify the optimal combination for the maximal tumor growth inhibition and yet staying under the toxicity constraint curve. His final example looked at a more complicated versus simplified QSP approaches to explore different aspects of the effect of reduced dose and increased dose- intervals on the anti-tumor efficacy of a monoclonal antibody. (For Dr. Bottino’s Slide, please click here).
Our second speaker, Dr. Frank Gibbons, highlighted the importance of 5R's in cancer drug development; i) Right Target/Efficacy, ii) Right Tissue/exposure, iii) Right safety, iv) Right patients and v) Right Commercial Value. Dr. Gibbons presented 3 case studies that showed how complicated QSP models evolve by integrating mechanistic models to answer particular research questions and achieve some of the five R’s. The first two case studies used integration of in vitro and in vivo data for: a) dose selection by predicting efficacy in humans where human PD data was not available, and b) lead optimization. The third case study showed the role of M&S in prediction of combining different treatment modalities citing an example of ionization radiation being combined with an investigational drug using a cell cycle model to better understand cell response. (We are not able to provide Dr. Gibbons slides for confidentiality reasons).
Dr. Gibbons also emphasized the need for an efficient repository of data and knowledge generated over time. When it comes to cancer drug development “we don’t know what we know”. He argued that diversity of compounds, dose and schedule, proper integration of research data, teamwork, and critical decision making capabilities are needed to answer the question of what we don’t know.
Most of the event attendees were researchers and leaders of pharmaceutical/biotech R&D in greater Boston area. Following the presentation, all attendees enjoyed craft beer and pizza at the Venture café, courtesy of Takeda pharmaceuticals. The event provided a great opportunity for learning, sharing, and building a community dedicated to advancing the field of QSP.
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Our next event is scheduled for July 19th. Our events are free. RSVP is required.
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