Ann: Bisantrene Highly Active in a Multiple Myeloma Mouse Model, page-34

1. Not really. The mice are so sensitive to carfilzomib (i.e. it is very toxic in these mice) that it is impossible to get enough carfilzomib on its own into a mouse model of MM to see an on-tumour effect.

2. See 1. Unfortunately, not all drugs have good animal models.

3. Given carfilzomib is efficacious in humans on its own then the combination is expected to show more effect in humans than in mice. The fact that adding what is a totally non-effective dose of carfilizomib to bisantrene improves the overall efficacy is very encouraging. Of course until you get to testing it in humans you are never certain, but everything is pointing in the right direction.

4. Even if the activity of the combination is just additive and not synergistic the combination of improved anticancer activity and lower cardiotoxicity would be commercially attractive. The Triangle report found that you need very little additional anticancer efficacy to be attractive to a drug that offers cardioprotection.