Montreal, Canada, October 1, 2012 – MethylGene Inc. (TSX: MYG) announced that clinical data from its MGCD265 Met/VEGFR-targeted oncology program were presented today at the European Society for Medical Oncology (ESMO) 2012 Congress, held in Vienna, Austria. Three poster presentations provided updates on the ongoing monotherapy, combination therapy and healthy volunteer trials.
“These data demonstrate the clinical activity of MGCD265 as well as its distinct profile relative to other Met-targeted agents.” said Dr. Rachel Humphrey, Executive Vice President and Chief Medical Officer of MethylGene. “The continued favorable safety profile at clinically relevant exposures and the preliminary signs of clinical benefit are encouraging.”
The poster entitled “A Phase I, dose-escalation study of MGCD265, a multi-targeted oral tyrosine kinase receptor inhibitor, for treatment of advanced solid tumors” (abstract 471P) documented the safety profile, pharmacokinetics, pharmacodynamics and clinical response observed to date in the ongoing monotherapy Trial 265-101. MGCD265 continues to exhibit a favorable safety profile with drug-related adverse events being mostly mild to moderate. The maximum tolerated dose (MTD) has not yet been reached. Drug-related grade 3 adverse events seen in more than one patient were diarrhea, fatigue and elevated lipase (n=2 for each). Stable disease was achieved in 36% of patients (24/67 patients). No objective responses have been seen to date. Dose-dependent Met inhibition was demonstrated using samples of patient plasma, and drug exposures have reached the range shown to have antitumor effects in animal models.
Data from the ongoing combination Trial 265-103 was presented in the poster entitled “Clinical effects of MGCD265, an oral tyrosine kinase inhibitor, in combination with erlotinib or docetaxel for treatment of advanced gastroesophageal and NSCLC tumors” (abstract 492P). This poster highlighted the clinical responses seen in patients with non-small cell lung cancer (NSCLC, n=12) or gastro-esophageal cancer (GE, n=9) treated with MGCD265 in combination with docetaxel or erlotinib in an ongoing dose-escalating Phase I study. Among twelve patients with NSCLC treated with MGCD265 (up to 600 mg / m2), nine achieved disease control (seven stable disease and two partial responses). Four NSCLC patients were progression-free for 7-11 months. In the GE cohort, five of nine patients treated with MGCD265 (up to 324 mg / m2) achieved disease control (all stable disease). Three of these patients remained stable for 11-22 months, an increase of 6-11 fold compared to the length of time on prior therapy. The safety profile of MGCD265 in combination with docetaxel or erlotinib was acceptable at doses up to 600 mg / day with no apparent increase in frequency of the adverse events that are commonly associated with docetaxel and erlotinib, respectively. Dose escalation is ongoing and the MTD has not been defined for either combination.
The third poster entitled “Pharmacokinetic profile of MGCD265, an oral tyrosine kinase inhibitor, with or without food in healthy volunteers” (abstract 493P) described the recently completed Phase I Trial 265-105 which assessed the effect of food on MGCD265 pharmacokinetics. This study showed that administration of MGCD265 in the presence of food increased drug exposure significantly, with no added toxicity. Based on these findings, food has been incorporated into all ongoing MGCD265 clinical trials.
All three posters are available on our website at http://methylgene.com/mgcd265/mgcd265-posters-publications.
MGCD265, a rationally designed, orally administered small molecule kinase inhibitor designed to target Met and VEGFR 1,2, and 3 receptor tyrosine kinases (RTKs). RTKs, including Met, are key kinases involved in cancer, angiogenesis (a process whereby new blood vessels are formed to nourish the tumors), tumor cell metastasis, tumor development and survival. Met expression is elevated and associated with tumorigenesis in several solid tumor indications including NSCLC, gastric, prostate, colorectal, bladder, breast and ovarian cancers. Two clinical trials (Phase I and Phase I/II) are ongoing using the agent as a monotherapy and in combination with erlotinib or docetaxel in solid tumors.
MethylGene Inc. (TSX:MYG) is a small molecule drug development company that is advancing two novel therapeutics for cancer and infectious disease in human clinical trials. The Company’s lead product candidates are: MGCD290, an oral antifungal agent targeting the fungal Hos2 enzyme that is currently in Phase II trials for vulvovaginal candidiasis, and MGCD265, an oral Met/VEGF receptor kinase inhibitor that is in Phase I/II clinical trials for patients with solid tumors. MethylGene owns all rights to its lead product candidates, and has partnerships with Otsuka Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., and EnVivo Pharmaceuticals, Inc. for its other pipeline programs.
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