FDA accepted the amendment to the NDA 9/07; received marketing approval for use after high-dose methotrexate therapy 3/08

Reached agreement with FDA on pivotal trial design 3/07; started its pivotal Phase III trials 5/07; began enrolling patients into its second and final pivotal Phase III trial 9/07

Reached agreement with FDA on SPA for pivotal Phase III trial 7/05; completed enrollment in pivotal Phase III trial 11/06; drug failed to meet the primary endpoint 9/07

Started two Phase III and non-small-

Starting a Phase III trial under FDA SPA that will evaluate the agent against placebo in 400 patients 5/06; completed enrollment in its pivotal Phase III trial 3/07; topline data showed it hit statistical significance in daily pain scores 7/07; treated the first patient in a pivotal registration Phase III trial 3/08

Company filed a response with the FDA to address issues the agency raised when it placed a Phase IIb trial on hold due to toxicology data 3/08; company is moving into a Phase II/III trial in a small subset of patients 2/09

Began Phase III program 10/03; pivotal Phase III trial failed to show statistical significance 9/05; a second Phase III trial achieved statistical significance at both doses and against both primary endpoints 5/07

First of three Phase III trials failed to demonstrate efficacy for both primary and secondary endpoints 8/06; Study 09, the second of three Phase III trials, showed no meaningful improvement vs. placebo and did not meet secondary endpoints 9/06; completed patient enrollment in the third of three Phase III trials 11/06; the last of three Phase III trials failed to meet its primary endpoint 3/07; began its fourth Phase III trial 3/08

Began pivotal Phase III trial to evaluate safety and efficacy and to discover biomarkers in 400 patients with major depressive disorder 3/06; completed enrollment in a pivotal Phase III study 3/07; Phase III study hit its primary endpoint 9/07; Phase III data showed it had an adverse event profile with effects on sexual function compared to placebo 3/09

FDA accepted the revised NDA 6/08

Started dosing in the first of two pivotal Phase III studies 2/08

Phase III data demonstrated significant improvement in opioid-tolerant patients 1/07; Phase III trial showed it is beneficial 5/07; data from a third Phase III trial showed statistically significant improvements in pain intensity 8/07; submitted an sNDA 11/07; FDA accepted the sNDA 1/08; FDA advisers voted against approval for the expanded indication 5/08; FDA issued a complete response saying it would not approve an expanded indication until the company implements and demonstrates effectiveness

Phase III trial didn't reach statistical significance on primary endpoints 6/06

Phase III trial showed statistically significant analgesia 9/04; final data confirmed benefit 1/05; pivotal Phase III data from a European trial showed it did not reach statistical significance in the primary endpoint of overall reduction of nausea and vomiting but did show it as good as morphine in terms of analgesia 2/07; additional data from pivotal Phase III trial showed fewer anti-emetic drugs were required in M6G patients vs. morphine patients, and M6G had a long duration of analgesic

An open-label extension study of a Phase III program showed that, of 20 subjects, 11 had reduced their dexamethasone dosage and two took no concomitant sexamethasone 11/06; Phase III data showed that long-term therapy appears safe and well tolerated, and is associated with reduced exposure to dexamethasone overall, resolution or improvement in associated steroid side effects and neurological stability or improvement 6/07

Plans NDA filing following positive Phase III 12/04; FDA accepted filing of NDA 12/05; FDA extended NDA review time, and Oct. 31 is the new PDUFA date 6/06; filed for approval in Germany, Austria and Spain 03/07

A 30-day waiting period for its IND application has elapsed 11/06

Phase III trial achieved its primary endpoint of demonstrating bioequivalence and achieved secondary endpoints 2/06; received a not-approvable letter because Phase III trials failed to demonstrate bioequivalence in certain areas 5/07

Began Phase III safety and non-inferiority program 1/05; began BLA filing process with FDA 10/06