Synta Pharmaceuticals Corp., a biopharmaceutical company focused on discovering, developing, and commercializing small molecule drugs to treat severe medical conditions, announced that it has achieved an operational milestone triggering a $10 million payment from GlaxoSmithKline (GSK) under its collaboration agreement for the development and commercialization of elesclomol.
Elesclomol is an investigational first-in-class oxidative stress inducer that triggers apoptosis (programmed cell death) in cancer cells. Elesclomol is currently being studied in combination with paclitaxel in a phase 3 clinical trial (SYMMETRY(SM)) in metastatic melanoma which completed enrolment earlier this month. Elesclomol is not yet approved for any indication in any market.
Synta has earned a total of $130 million in payments from GSK to date, including the $80 million upfront payment in 2007, $40 million for milestones achieved in 2008 and the $10 million announced for the achievement of a melanoma-related operational milestone. Under the collaboration agreement with GSK, Synta is eligible for a total of $585 million in pre-commercial milestone payments, of which $50 million have been paid to date, $100 million are related to additional progress in melanoma, and the remainder is related to progress in other cancer indications. In additional to the pre-commercial milestone payments, Synta is eligible for $300 million in sales milestones, 40-50 per cent share of operating profits in the United States, and double-digit royalties on sales outside the United States.
Elesclomol is an investigational first-in-class oxidative stress inducer that triggers apoptosis (programmed cell death) in cancer cells. Cancer cells operate at high levels of reactive oxygen species, or oxidative stress. Elesclomol acts by increasing the level of oxidative stress in cancer cells even further, beyond sustainable levels, inducing apoptosis. This mechanism of action, called oxidative stress induction, represents a novel way of selectively targeting and killing cancer cells.
In a double-blind, randomized, controlled Phase 2b clinical trial in 81 patients with stage IV metastatic melanoma, elesclomol in combination with paclitaxel met the primary endpoint, doubling the median time patients survived without their disease progressing, compared to paclitaxel alone (p = 0.035). The most common adverse events in the elesclomol plus paclitaxel group included fatigue, alopecia, constipation, nausea, hypoaesthesia, arthralgia, insomnia, diarrhoea, and anaemia.
A pivotal phase 3 clinical trial of elesclomol in combination with paclitaxel in patients with stage IV metastatic melanoma (the SYMMETRY trial) has completed enrolment; a phase 1/2 trial in hormone-refractory prostate cancer, in combination with docetaxel, is ongoing. A phase 1 monotherapy trial in solid tumours was recently initiated and phase 2 trials in other indications, and in combination with other agents, are planned.
In October 2007, Synta and GSK entered into a collaboration agreement for elesclomol. Under the terms of the agreement, the companies will jointly develop and commercialize elesclomol in the U.S. and GSK will have exclusive responsibility for development and commercialization of elesclomol outside the US. Synta is responsible for the SYMMETRY phase 3 melanoma study and the filing of the New Drug Application with the FDA.
Synta and GSK are working closely together to further the clinical development of elesclomol as well as prepare for the manufacture and commercial launch of elesclomol.
Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on discovering, developing, and commercializing small molecule drugs to extend and enhance the lives of patients with severe medical conditions, including cancer and chronic inflammatory diseases.