Myriad use these words to define Azixa.Results of phase I are very positive and myriad will release news soon.Azixa is effective at very low dose against multidrug resistance cells not only in preclinical trials.
Myriad Genetics' Cancer Compound MPC-6827 Causes Tumor Regression in Pancreatic Cancers
- Data to Be Presented at Upcoming AACR Cancer Conference -
SALT LAKE CITY, Jan. 20 /PRNewswire-FirstCall/ -- Myriad Genetics, Inc. (Nasdaq: MYGN), today announced results of preclinical testing with its new pro-apoptotic compound, MPC-6827. This novel compound was discovered through the application of a caspase-based, high throughput screening system by Maxim Pharmaceuticals, Inc. and a subsequent medicinal chemistry program. Myriad is completing the toxicology, CMC and pharmacokinetic data required for submission to the FDA to register MPC-6827 as an Investigational New Drug (IND).
Myriad tested MPC-6827 against pancreatic tumors in a xenograft mouse model to mimic the human form of the disease. One group of mice was treated with 80 mg/kg of gemcitabine, the standard of care in pancreatic cancer chemotherapy, and the other group was treated with 5 mg/kg of MPC-6827. All treated mice showed statistically significant inhibition of tumor growth. However, MPC-6827 demonstrated a 38% inhibition of tumor growth, while gemcitabine showed just a 17% inhibition of tumor growth, compared with controls. In pancreatic tumors, the compound was twice as effective as gemcitabine, and achieved this improved efficacy at a significantly lower dose.
MPC-6827 also performed well in testing against other tumor types in xenograft models. In melanoma tumors, one group of mice was treated with 25 mg/kg of paclitaxel and the other group was treated with 5 mg/kg of MPC-6827. The activity of MPC-6827 was greater than that observed with paclitaxel. More significantly, MPC-6827 treated mice had twice the survival rate compared with the paclitaxel treated mice. At the conclusion of the study, 60% of the MPC-6827 treated mice had survived the cancer, versus only 30% for the paclitaxel treated group and just 10% of the controls. The improved survival with MPC-6827 treated mice versus the control animals achieved statistical significance at a value of p=0.0002.
In a breast cancer xenograft model, three groups of mice were given MPC-6827 at doses ranging from 5 mg/kg to 10 mg/kg. In each cohort of animals, MPC-6827 completely halted the progression of breast cancer tumors, while the untreated control mice experienced a 1000% increase in tumor size.
"As a cancer researcher and scientific advisor to cancer drug developers, I have reviewed the preclinical data of a great many compounds," said Daniel Von Hoff, M.D., Executive Vice President of the Translational Genomics Research Institute (TGen) and Director of the Cancer Therapeutics Program at the Arizona Health Sciences Center. "MPC-6827 is certainly the best preclinical candidate that I have seen in several years. Based on the remarkable efficacy data in cell-based and xenograft models, I feel confident that this molecule will be active in humans."
Good news are coming.Milestone payment for epct,but above all validation of the entire drug discovery platform.
Myriad Initiates Phase 1 Trial of MPC-6827 in Metastatic Brain Cancer
- Preclinical Data to be Presented at AACR Conference -
SALT LAKE CITY, March 1 /PRNewswire-FirstCall/ -- Myriad Genetics, Inc. (Nasdaq: MYGN), announced today that it will begin a second Phase I clinical trial with its investigative cancer drug, MPC-6827, under an FDA-approved Investigational New Drug application. This new human clinical study will evaluate the potential of MPC-6827 to treat metastatic brain cancer by achieving therapeutic concentrations in the brain that are sufficient to treat tumors without significant systemic exposure or toxicity. The Phase 1 clinical study will be performed at Memorial Sloan-Kettering Cancer Center in New York City.
In preclinical studies, MPC-6827 was demonstrated to reach approximately 1500% greater concentration in the brain than in the blood. This high brain concentration was achieved at a safe therapeutic dose for the treatment of peripheral tumors in mice. Importantly however, we believe that a much lower dose in humans should result in brain concentrations of MPC-6827 sufficient for anti-tumor activity yet without peripheral toxicity. The highest brain penetration percentage of drugs that are currently used in treating brain cancer is that of temozolomide, which reaches a peak brain concentration level that is just 29% of the blood plasma concentration. We believe that the strong and selective brain penetration of MPC-6827 suggests a special opportunity to study anti-tumor activity in patients with primary brain tumors and brain metastases that are resistant to current standard of care therapy.
"Treating brain tumors has proven to be one of the great challenges in cancer therapy," said Lauren E. Abrey, M.D., a board certified Neurologist and Clinical Neuro-Oncologist at Memorial Sloan-Kettering Cancer Center in New York City, and principal investigator on the Phase 1 study. "MPC-6827 has shown the potential to address this need due to its ability, in preclinical models, to cross the blood/brain barrier and achieve therapeutic levels."
The distribution of Myriad's cancer drug candidate into the brain was evaluated in mice by treating them with a single intravenous dose of MPC-6827. The time to maximum drug concentration of MPC-6827 was just three minutes in both blood plasma and brain tissue, indicating that MPC-6827 distributed rapidly into the CNS. Brain concentration of the drug candidate was approximately 15 times higher than the plasma concentration. At the maximum tolerated dose, the average concentrations in plasma and brain, over a 24-hour period, were approximately 118 nM and 1650 nM, respectively. The brain concentration of MPC-6827 was 825 times greater than the concentration required to activate caspase and induce the cancer cell killing apoptosis process in cancer cells in vitro. Importantly, MPC-6827 was cleared from the brain at a similar rate as from the blood. This preclinical data will be part of presentations made by Myriad on MPC-6827 during the 96th Annual Meeting of the American Association for Cancer Research, from April 16-20, 2005, in Anaheim, CA.
"We look forward to exploring the potential of MPC-6827 in the treatment of patients with brain tumors," said Adrian Hobden, Ph.D., President of Myriad Pharmaceuticals, Inc. "Myriad continues to advance its clinical development pipeline with investigational drug candidates that address areas of significant unmet medical need."