Thanks, kenhott; here's my notes:
Milestones for '07
CS-917: PIIb results 1H07 ==> P3 in late 07/early 08.
MB07803: P2 to start 1H07 (cs-917 2b data could provide proof of concept, driving interest in MB07803. "Major partnership potential."
MB07811: Single dose data due shortly. Q2 start multi-dose PIb. Some volunteers will have high LDL. "Major partnership potential."
MB07133; Initiate proof of concept study. "Partnership potential."
Pradefovir: PIII to begin soon (this year) with SP. Licensed worldwide. Better deal than Valeant.
Diabetes: Sankyo CS-917 Gluconeogenesis inhibitors (target FBPase (fructose 1,6-bisphosphate)). Only company in the space. Mostly 2nd line . . . Going after metformin failures/intolerant, & tolerant with GI SEs. Also, OAD failures, renally impaired, newly diagnosed (relatively small market). Also in combo with sensitizers and DPP-IV inhibitors.
MB07803 PI (nothing to add to above)
Hyperlipidemia: PI MB07811 Liver Targeted Selective Thyroid Receptor Agonists. previous drugs in this class have not had good therapeutic index (cv issues). TR Beta is the agonist target. Liver targeting widens therapeutic index. Shows 3x LDL lowering versus other TR agonists (KB-141), no obvious effects on CV system or thyroid hormone axis. Additive to statins. P1 dosing recently completed in rising single dose trial. In Q2, start multi-dose trial, for safety, and initial efficacy.
Hep B: Schering-plough, going into PIII this year Pradefovir. Liver targeted pro-drug of adefovir. Hepsera is also a prodrug of adefovir but is not liver specific, and dosing is sub-optimal because of renal toxicity. Liver specificity allows avoidance of renal toxicity. P2b 30mg dose showed undetectable virus at 48 weeks in 71% of patients versus 36% for Hepsera. 30mg dose goes to P3.
Obesity: (mentioned only in passing, no program mentioned; presume it would be a happy side effect of diabetes program, a la Byetta)
Liver Cancer: P1/2 MB01733 Again, a liver targeted version of an existing drug, cytarabine (araC). Activated form (araCMP) bypasses liver resistance mechanism, and gets into the liver. Normal cytarabine accumulates in bone marrow, leading to toxicity. P1/2 complete. 6 doses: 300, 600, 1200, 1800, 2400, & 3000 mg/m^2/day by IV infusion, on 28 day cycle. Cohorts of 3-6 patients per dose. well tolerated in inoperable HCC patients up to 2400. No drug-related AE to limit dosing. Plasma araC levels are low, suggesting good uptake in liver. [Question: how do they know, aside from AE rate, that it's not heading into marrow?]. 42% of patients completed 3 cycles, and 3 patients completed at least 12 cycles. Evidence of shrinkage, particularly after 3 cycles.
All 5 clinical candidates internally discovered; own 3; co-promotion rights except pradefovir.
Add to other companies compounds: Merck (Hep C), Idenix (Hep C)
Cheers, Tuck |
