Project: Development of a balanced dual PI3K/mTOR kinase inhibitor: A new generation of potential drugs for targeted cancer therapy
Cancer represents a major unmet medical need in society today for which the treatments have limited success and, in some cases, high toxicity. There is a need for additional targeted therapies that will deliver better and longer lasting responses. Therefore PI3K and/or mTOR inhibitors are being developed as targeted therapies for the treatment of cancers that depend on the PI3K/AKT/mTOR pathway which is an accepted and validated drug target with a sizeable market potential in both oncological as well as non-oncological indications._x000D_ _x000D_It is PIQUR’s goal to develop novel innovative dual PI3K/mTOR inhibitors to treat cancers with deregulated PI3K/AKT/mTOR pathways. In order to do this PIQUR will collaborate with the Dutch company, "WIL Research Europe B.V." (WIL), for their preclinical expertise in the areas of pre-clinical and toxicological profiling and their experience with kinase inhibitors. PIQUR and WIL have an established collaboration for nearly 2 years and have successfully executed several research and development projects which has strengthened their position in this competitive field. _x000D__x000D__x000D_GENERAL INFORMATION REGARDING PQR309_x000D_PIQUR has designed and developed the dual PI3K/mTOR inhibitor PQR309, for the treatment of cancer with dysregulated PI3K/AKT/mTOR pathway. PQR309 has superior properties compared to most advanced competitors with respect to selectivity profile, pharmacological as well as drug like properties. The good oral bioavailability combined with good exposure in the brain makes PQR309 an ideal compound to treat various cancers including difficult to treat brain tumors and brain metastasis. The ongoing clinical development of competitor compounds provides PIQUR with the advantage of a “free” benchmark for efficacy and safety. PIQUR owns the IP for PQR309, which is expected to profit from the synergism of its balanced dual PI3K/mTOR inhibition profile._x000D__x000D__x000D_DEVELOPMENT OF PQR309_x000D_PQR309 will be developed for entry into clinical Phase I studies. Additionally, added value will be generated in the form of novel technologies to better evaluate protein kinase inhibitor drugs in the preclinical and regulatory phase, and suitable biomarkers will be developed that will facilitate patient stratification and prediction of therapeutic responses._x000D__x000D_The Phase I clinical trial with PQR309 will be performed in collaboration with the Swiss Group for Clinical Cancer Research (SAKK) and with the joint support of WIL who, in addition to preclinical safety and toxicity profiling, will be responsible for the pharmacokinetic analysis of samples taken during Phase I. The study will be conducted in pre-treated cancer patients with advanced solid tumours for whom there is no further effective treatment available. The Part A of Phase I will be conducted at four sites in Switzerland, while the Part B of Phase I will be conducted in Switzerland, Spain and in the UK. _x000D__x000D_The first CO objective of the study (Ph IA) is to define the Maximum Tolerated Dose (MTD) and the biologically effective dose in patients in order to obtain a safety profile of PQR309. In a second step (Ph IB), the maximal biologically effective doses will be established and preliminary efficacy data will be collected in selected patient cohorts that are most likely to respond to PQR309 (patients with PIK3CAmutations, PTENnull, activated Ras and/or overexpressed receptor tyrosine kinases). The outcome of this study will allow PIQUR to proceed to further development and eventual marketing of PQR309. The expansion to Phase B of the trial, which is not being funded as part of this application, will provide convincing evidence of a high response rate to PQR309 in one or more selected patient populations. PIQUR will apply the novel ICH S9 guideline for development of anticancer agents and intends to use a "Fast Track' mechanism to accelerate market entry of its new targeted cancer therapy PQR309. _x000D__x000D__x000D__x000D_
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Acronym
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PQR309
(Reference Number: 8328)
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Duration
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01/08/2013 - 30/09/2015
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Project Topic
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The project aims to develop a new generation of targeted cancer therapeutics. PIQUR has identified a novel, innovative, dual PI3K/mTOR inhibitor comparing favourably with the most advanced clinical compounds with respect to off-target profile and pharmacological properties.
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Network
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Eurostars
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Call
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Eurostars Cut-Off 10
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Project partner
