Biotech Values

[DewDiligence]

Musings on the M118 phase-2b program:

Would this trial be registrational, and if not why?

A phase-2b trial will not support an NDA on its own, but it could conceivably be one of two registrational studies for M118 in the ACS indication, depending on the trial design.

It certainly sounds like the trial would be sufficiently large, and the endpoint will be suitable. I assume they have decided on a dose / schedule. Are there any other variables I am missing?

MNTA has not publicly disclosed the design of the phase-2b trial(s) they intend to run, but my expectations are roughly as follows.

• Primary endpoint: The event rate at six months for a composite of death, MI, stroke, and revascularization. (In the Phase-2a EMINENCE study, the composite endpoint also included bleeding events and was measured at one month.)

• Comparator: Placebo, UFH, or Angiomax (with patients in all arms receiving standard antiplatelet therapy). If the comparator is placebo, M118 will have to show statsig superiority on the primary endpoint without statsig worse bleeding to be deemed a success; if the comparator is UFH or Angiomax , M118 will have to show statisg non-inferiority on the primary endpoint and at least a trend toward superiority (i.e. p<0.15), without statsig worse bleeding. (In the EMINENCE study, M118 was statsig non-inferior to UFH.)

• Dose: 50 IU/kg, the lowest dose in the EMINENCE study, and either 75 or 100 IU/kg (the other two doses in the EMINENCE study). (In the EMINENCE study, the 50 IU/kg arm did the best on the primary endpoint, but this was likely a fluke.)

Comments?