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Researchers from M&S Decisions LLC shared their experience in mathematical modeling of bile acids enterohepatic circulation and the industrialization of systems pharmacology model development by presenting two scientific works on PAGE 2018 Conference in Montreux, Switzerland, after participating in a full-day modeling workshop organized by IntiQuan company:

• A functional, integrative R environment workflow for the development and use of quantitative systems pharmacology models presented by Artem Dolgun
• Using a physiologically-based QSP model to simulate the effects of enterohepatic circulation perturbations on the distribution of bile acids presented by Veronika Voronova

A QSP model was used to show that gastric emptying inhibition by exenatide represents an important additional mechanism of postprandial glucose stabilization. The drug effect depends on the food properties, which underscores the importance of dietary counseling as an adjunct to medication.

Voronova V, Zhudenkov K, Penland RC, Boulton DW, Helmlinger G, Peskov K. Exenatide effects on gastric emptying rate and the glucose rate of appearance in plasma: A quantitative assessment using an integrative systems pharmacology model. Diabetes Obes Metab. 2018; 1–5. 

Researchers from M&S Decisions made a presentation, summarizing usage of multiple quantitative clinical pharmacology methodologies on different stages of drug development.

M&S Decisions took part in the Annual Meeting of American Association of Cancer Research 2018 where we presented a work “Quantitative modeling as a systematic approach for drug combination evaluation in Immuno-Oncology”.

A mechanistic model describing interactions among host immune cells and tumor cells was developed. The proposed model was used to explore the effects of PD-1 and CTLA-4 immune checkpoint inhibitors, OX40 agonistic ligand and CXCR2 blocking antibody, and their combinations, on tumor microenvironment and tumor growth dynamics in various experimental murine models. The types of synergistic effects which may arise from immuno-oncology drug combinations were categorized across realistic baseline conditions prevailing in the tumor microenvironment (TME).

M&S Decisions LLC presented two systems pharmacology models developed in collaboration with AstraZeneca at ASCPT 2018 Annual Meeting, one of the biggest clinical pharmacology conferences in the US:

• Differentiation of anti-PCSK9 antibodies and synthesis inhibitors: a drug-disease modeling study presented by Victor Sokolov
• Contribution and regulation of SGLT1 and SGLT2 in healthy and type 2 diabetes subjects: a drug-disease modeling study presented by Tatiana Yakovleva

Also during the session about Immuno-Oncology therapeutic combinations key results of collaboration between AstraZeneca company and M&S Decisions LLC were presented by Gabriel Helmlinger in a talk “Quantitative Systems Pharmacology Modeling to Inform Combination Strategies in Immuno-Oncology”.

Researchers from M&S Decisions shared their experience in usage of QSP, PBPK, pop-PK/PD modeling in optimization of clinical trial design.

New article about immuno-oncology QSP modeling was just published in the Journal of ImmunoTherapy of Cancer.

A mathematical model is presented. It integrates key mechanistic features of immuno-oncology biology, radiation and anti PD-L1 pharmacokinetics, to accurately predict optimal radiation and anti PD-L1 dose sequencing for maximal anti tumor efficacy. Owing to its mechanistic nature, the model features mechanistic insights into the immune-suppressive vs. immuno-activating forces underlying dose sequencing optimization.

Yu. Kosinsky, S. Dovedi, K. Peskov, V. Voronova, L. Chu, H. Tomkinson, N. Al-Huniti, D. Stanski, G. Helmlinger. (2018) Radiation and PD-(L)1 treatment combinations: immune response and dose optimization via a predictive systems model, Journal for ImmunoTherapy of Cancer (2018) 6:17

Yuri Kosinsky and Oleg Stepanov, researchers from M&S Decisions, gave practical training “Introduction to pharmacometrics and population analysis” for young scientists at Future Biotech Winter Retreat 2018.

The Big Data in Pharma conference aimed the overview of the big data spectrum in pharmaceutical development and the ways of its utilization.

M&S Decisions took part in this conference and Kirill Zhudenkov gave a report on the decision making in drug development.

M&S Decisions, Skolkovo Biomedical cluster and Open Skolkovo University held a 4-day conference and workshop, devoted to the mathematical modeling in drug development. The event was targeted to the PhD students, postdocs and young scientists.

The wide set of topics was presented and studied: the principles of model-based drug development, the basics of PBPK, quantitative systems pharmacology, pharmacometrics etc. The attendees of the conference collected unique experience of working in modern R&D projects for  innovative drugs.

During the XXI Russian Congress on Oncology a special session was devoted to the presentation of Skolkovo startups performing the research in oncology. Yuri Kosinsky from M&S Decisions gave a presentation on the research of IO+RT in terms of immune response and dose regimen optimization.

Pharmacokinetics UK (PKUK) was a spin out from the DMDG (Drug Metabolism Discussion Group) in the early 80s. Since those times the conference is held on the early basis in the UK.

M&S Decisions attended the PKUK Meeting 2017, where Yuri Kosinsky made a report on radiation and anti-PD-L1 treatment combinations.

The annual Open Innovations forum has been held in Moscow since 2012 under the aegis of the Government of the Russian Federation and is considered a unique discussion platform for participants in the formation of an innovative ecosystem.

M&S Decisions attended the Open Innovations forum in Skolkovo. Kirill Peskov took part in the discussion session “To keep pace with technologies. How to regulate new medicine?”

M&S Decisions attended the ACoP 2017 conference, where presented a set of works devoted to the investigation of modeling methodology and disease areas: metabolic, respiratory and oncology.

M&S Decisions attended the 3rd AstraZeneca-MedImmune-CRUK Cancer Symposium, Cambridge, UK.

Kirill Peskov, CEO M&S Decisions LLC, presented the work “Radiation and anti-PD-(L)1 treatment combinations: Immune cell responses and dose scheduling optimization using a joint experimental and systems modeling approach” made by M&S Decisions in collaboration with AstraZeneca and MedImmune.

This project is aimed at recruiting young biomedical technology staff for employment and traineeships at companies participating in the Biomedical Technologies Cluster, pharmaceutical manufacturers, and the Skolkovo Foundation.

M&S Decisions took part in this event, established new communications and selected several candidates for the new position in the company.

Our company has open positions. The details are available at HH, Molbiol, LinkedIn or M&S Decisions website – Career page.

Victor Sokolov, a researcher from M&S Decisions LLC, presented the work “Comparison of Lipid-Lowering Properties of Anti-PCSK9 Antibodies and Synthesis Inhibitors Using a Quantitative Systems Model of Lipoprotein Metabolism”  made by M&S Decisions in collaboration with AstraZeneca at Scientific Sessions of American Diabetic Association (ADA), San Diego, USA

Researchers from M&S Decisions LLC in collaboration with Astrazeneca made four scientific presentations at PAGE 2017 conference in Budapest, Hungary, one of the largest pharmaceutical modeling conferences in Europe.

The M&S Decisions researchers presented the following talks and posters:

• Joint modeling of overall survival and tumor size dynamics in non-small cell lung cancer: Clinical trial simulations and validation of predictions at study and subject levels, presented by Dmitry Onishchenko
• Radiation and anti-PD-L1 treatment combinations: Immune cell responses and dose scheduling optimization using a joint experimental and systems modeling approach, presented by Yuri Kosinsky
• Inhibition of bile acids synthesis via fibroblast growth factor 19 (FGF19) through intestinal signaling: A population analysis, presented by Dina Chernikova
• Evaluation of immediate release exenatide effects on gastric motility and intestinal glucose absorption using a systems pharmacology model, presented by Veronika Voronova

Veronika Voronova, a researcher from M&S Decisions LLC, presented the work “Systems Pharmacology Modeling of Bile Acid Distribution and Signaling”  made by M&S Decisions in collaboration with AstraZeneca and Karolinska institute, Sweden at Keystone conference: Bile Acid Receptors as Signal Integrators in Liver and Metabolism in Monterey, USA.

M&S Decisions LLC presented work made in collaboration with AstraZeneca “Model-based meta-analysis of safety for immune checkpoint inhibitor combinations and monotherapy” at ASCO-SITC Immuno-Oncology Symposium at Orlando, USA

M&S Decisions together with Skolkovo Biomedical technologies cluster and Skolkovo Open university have organized the school on Mathematical modelling in pharmaceutics for biomedical startups and young scientists at Skolkovo Foundation.

The aim of the school was to introduce to the participants the core methods of mathematical modelling, which are widely used for decisions making process during new drugs development.

More than 200 young specialists took part in the event, including undergraduate and post-graduate students from leading Russian universities such as Moscow State University, Moscow Institute of Physics and Technology, Mendeleev University of Chemical Technology, Sechenov First Moscow State Medical University, National Research Medical University, Mechnikov North-Western University, Altai State University and others.

On the first day of the school the Skolkovo Hypercube brought together specialists from different areas of biology, chemistry and medicine where mathematical model is actively used. Young scientist had lectures on methods how mathematical modelling is used on different stages of drugs development including:

• different phases of clinical and preclinical trials
• making decisions at drug development
• special focus was made on immuno-oncological research

The second and the third days of the school were devoted to lections and practical trainings in Pharmacometrics, Systems Pharmacology and Translation modelling.

Kirill Peskov and Yuri Kosinsky, lead scientists at M&S Decisions, participated in the scientific seminar at the FDA, a federal agency responsible for the regulation and supervision of pharmaceutical drugs in the U.S.A. The seminar was focused on innovative methods in mathematical modeling, to improve the therapeutic outcome of novel drugs in the treatment of cancer. A new quantitative methodological platform, developed in collaboration between Skolkovo resident M&S Decisions and the pharmaceutical company Astrazeneca, was presented. The platform included a combination of modeling approaches, including systems pharmacology, pharmacometrics, and meta-analyses. It is under further development and validation work to predictively assess the therapeutic potential of novel oncology drug combinations, including the prediction of key endpoints in drug development clinical trials.

Such combination of modeling approaches results in the creation of a ‘modeling continuum’ along the pharmaceutical R&D pipeline, thereby enabling constant support towards decision-making, from preclinical to first-in-human trials, and from such early clinical trials to late-phase and registration trials. ‘How’ and ‘where’ in the pipeline such quantitative modeling may support transition points and decisions, and how it may help better identify patient subpopulations who respond to specific combination therapies, were debated in a lively and interactive Q&A session that followed the presentation, and during which the overall methodology platform was seen as “progressive.”

Researchers from M&S Decisions LLC made three scientific publications at ICSB 2016 conference in Barcelona, Spain, which is the largest European conference on Systems Biology.

The M&S Decisions researchers presented the oral talks and two posters:

• Quantitative Systems Pharmacology model for immuno-oncology drug development: example of CTLA4 inhibition mechanism, presented by Yuri Kosinsky
• Enhancement of cytokine signaling via cytokine-neutralizing antibodies, presented by Boris Shulgin
• A quantitative systems pharmacology model to explore combination efficacy of immuno-oncology compounds: Effects of CXCR2 and PD-1 inhibitions, presented by Kirill Peskov

Researchers from M&S Decisions LLC made six scientific publications at PAGE 2016 conference in Lisboa, Portugal, which is one of the largest pharmaceutical modeling conferences in Europe.

The M&S Decisions researchers presented the following talks and posters:

• Investigation of anti-CTLA-4 immuno-oncology therapy through a quantitative systems pharmacology model, presented by Kirill Peskov
• A Markov Chain model to characterize cataract progression and disease burden in the Russian Federation, presented by Kirill Zhudenkov
• A mechanistic PKPD model relating early asthmatic response to anti-leukotriene drug PK and biomarker levels in allergen challenge studies, presented by Victor Sokolov
• A quantitative systems pharmacology model to explore combination efficacy of immuno-oncology compounds: Effects of CXCR2 and PD-1 inhibitions, presented by Oleg Stepanov
• Investigation of the diabetes-related metabolic memory phenomenon using a quantitative systems pharmacology approach, presented by Veronika Voronova
• A systems pharmacology model of SGLT2 and SGLT1 inhibition to understand mechanism and quantification of urinary glucose excretion after treatment with Dapagliflozin, Canagliflozin and Empagliflozin, presented by Tatiana Yakovleva

Researchers from Moscow Institute of Physics and Technology, M&S Decisions LLC and Yandex LLC built a computer agent based model of the interaction between different bacteria, and between bacteria and the gut wall. This has led them to explain how antibiotic-resistant microbes develop and spread; details of the study have been published in the journal PLOS ONE.

The human intestine contains trillions of different bacteria, which together are called the microbiome. Bacteria protect us from harmful microorganisms, produce digestive enzymes, and help the immune system to function normally. Many diseases, such as obesity, Crohn’s disease, colon cancer, and other inflammatory processes are associated with a change in the gut microbiome. The researchers built a model of the interaction between two types of bacteria and the intestine and they determined what happens when antibiotics are taken that kill a large number of microorganisms.

Source: MIPT press release

Kirill Peskov, Managing Director and Senior Principal Scientist of M&S Decisions LLC presented a lecture on topic  “Pharmacometrics and model based drug development” at Pharma Cool School organised by Skolkovo foundation.  Read more