Date: 2015-04-17
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting, in Philadelphia, Pennsylvania, April 18-22, 2015
Company: Piqur Therapeutics (Switzerland)
Product: PQR309
Action
mechanism: kinase ihibitor/mTOR inhibitor. PQR309 is an orally bioavailable pan inhibitor of phosphoinositide-3-kinases (PI3K) and inhibitor of the mammalian target of rapamycin (mTOR), with potential antineoplastic activity. PQR309 inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a lesser extent, mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy. As mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K, this agent may potentially be more potent than an agent that inhibits either PI3K kinase or mTOR kinase. By inhibiting mTOR to a lesser extent than PI3K, PQR309 does not interfere with the mTOR-mediated negative feedback loop on PI3K signaling. Blocking the negative feedback loop would potentially increase PI3K signaling and decrease therapeutic efficacy.
Disease: advanced solid tumors
Therapeutic area: Cancer - Oncology
Country: Switzerland, UK
Trial
details: This study is a Phase I, open label study to determine the Maximum Tolerated Dose(MTD) and the Recommended Phase II Dose (RP2D) in patients with advanced solid tumors. The trial will include 35 patients. (NCT01940133)
Latest
news: * On April 17, 2015, PIQUR Therapeutics announced that the company and its academic collaborators will present five posters highlighting preclinical as well as clinical data on PQR309, at the American Association for Cancer Research (AACR) Annual Meeting, which will take place in Philadelphia, Pennsylvania, April 18-22, 2015. Initial results from the first-in-man phase 1 trial indicate • “BKM120-mediated G2 arrest: Structural and functional segregation of off-target action and PI3K inhibition” Abstract Number 671 * On January 21, 2014, PIQUR Therapeutics AG has announced that it has received approval from the authorities in Switzerland and UK to conduct the clinical Phase I study with PQR309. This study will assess the safety in cancer patients, and will help determine the ideal dosage. On January 2, 2014, PQR309 was administered to the first patient at the University Hospital in Basel. Also of crucial importance for the future development of the company is the broadening of the license agreement with the University of Basel. The license agreement with the University of Basel was previously limited to the field of cancer, and has now been extended to a broad range of promising clinical indications. “The expansion of the license agreement is very important for the progress and development of our company. We now have the unlimited freedom to assess the therapeutic benefit of PQR309 and all other research programs in other therapeutic fields, such as immunology, neurology and ophthalmology,” pronounced Prof. Dr. Bernd Giese, Chairman of the Board of Directors.
that PQR309 is safe and well-tolerated with no significant side effects. In addition to the good safety data, PQR309 has also shown the first encouraging signs of clinical activity in solid tumors.
Following are the specifics of the abstracts, including session times and locations:
• “PQR309: Structure-based design, synthesis and biological evaluation of a novel, selective, dual pan-PI3K/mTOR inhibitor” [Poster Session: PI3K Pathway and Metabolism Modulators, Abstract Number 2664.
• “PQR309: A potent, brain-penetrant, dual pan-PI3K/mTOR inhibitor with excellent oral bioavailability and tolerability” [Poster Session: Pharmacokinetics and Pharmacodynamics. Abstract Number 4514
• “First-in-man (FIM) pharmacodynamic (PD) and pharmacokinetic (PK) phase I trial of PQR309 in advanced solid tumors” [Poster Session: Phase I Clinical Trials, Abstract Number CT310
• “Pre-clinical activity and mechanism of action of the novel dual PI3K/mTOR inhibitor PQR309 in B-cell lymphomas” [Poster Session: PI3K Pathway and Metabolism Modulators, Abstract Number 2652
