Biotech Values

[poorgradstudent]

Calibration and discussion questions if I may (not intended to be confrontational - truly a cal and discussion):

A) do you believe Provenge works? Ipilamumab?

B) if you do believe they work then what differentiates them from cldx's drug or others? What do you believe to be the smoking gun of efficacy?

My comments were directed towards rindopepimut, which I thought was the larger focus of the piece. So in regards to A, i would note that the mechanism of action of provenge and ipilimumab are very different that rindopepimut.

Rindopepimut is simply a 13 amino acid peptide attached to a carrier protein (KLH in this case). So the body has to ramp up an immune response against this peptide. This has historically been a relatively failing proposition in producing an adaptive immune response: you get low titre B-cell derived antigen specific antibodies and a weak T cell response. This is very similar to BLP25.

MAbs like ipilimumab skip the step of requiring the body to produce high affinity antibodies against the desired target. I think this is key. I do not debate ipilimumab's efficacy, but its mechanism is very different than what rindo asks of the immune system.

As for provenge, the earlier papers by Vuk-Pavlovic showed very weak T cell responses. And as we know, the response was largely against the fusion point of the constructed peptide cassette. I won't deny that provenge has demonstrated some efficacy, but I think we can agree that the mechanism through which that efficacy is manifest depends on a pathway very different than rindo.