1) it targets a mutated protein for which it might be easier to break tolerance.
2) They show that EGFRVIII positive tumors turn into EGFRVIII negative tumors - implies the vaccine has biologic activity.

Other than that it’s a highly risky program.

Ohad

A teaching fellow at the Mayo Clinic posted these remarks about CLDX’s Rindopepimut. Do you agree? What would be your rejoinder?

“I’ve not really looked into this, so I don’t have anything meaningful to add. I will note, however, that they’re using additional methods to stimulate T cells. I think this highlights the difference in approach between companies who simply believe this pathway will take care of itself (a la rindo) versus companies that believe direct stimulation of this pathway is a necessary part of improving the success of immunotherapeutics (ipi, blinatimumab).

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Not to belabour the point, but I think one important point of all these vaccine immunotherapeutics against self antigens is to pay attention to the immune response related side effects (if any). Since we’ve not had much success with vaccine-type immunotherapeutics, new approaches will most likely show outright failure (we see little to no immunological adverse events coupled with little efficacy - theratope and various other vaccine immunotherapeutics) or a degree of success that goes hand in hand with a serious immunological adverse event profile (ipilimumab; remember TGN1412?).

I don’t think we’re at the point technologically where we can manage to break self-tolerance with these vaccination strategies while demonstrating zero immunological adverse events. In my opinion, anyone currently selling this utopian view is selling a vaccine strategy that doesn’t work.”

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.

As per usual, I do not believe that such peptide immunotherapeutics elicit a sufficient immune response. I would personally stay away from cldx even if that means I miss out on a phase iii success.

I liked OSI’ new IGF1R inhibitor. Looks like they are the first to suceed with that target, probably have a better chance than all the antibodies in the clinic against the same target. However I am not too optimistic on Tarceva’s ability to grow, following the recent data at ASCO as a maintenance therapy.

I don’e have a concrete opinion on ONTY.

ohad

RICH

Regarding the MITI rumor, I also heard that but I have no confitrmation. If MITI manages to get full rights to blinatumomab, it will put it in a very attractive position. The $6M figure sounds rather low, though.

ohad

What do you think about NPSP? They have 2 drugs in phase 3: GATTEX™ (teduglutide), NPSP558 (parathyroid hormone 1-84 [rDNA origin] injection)

Thanks

Sorry, I don’t follow YMI

ohad

Prior valuation is irrelevant.

It is not like they produced positive results from phase 3 trials.

Also, what scares me is that incyte was once over a 140 per and has lost more than 95 percent from that high.

ohad

what is your opinion on INCY? Are you writing any article on INCY

Can’t you comment on this , why ?

The ARRY news is negative but it’s only one of many assets.

ohad

Thanks
Alex

Love your work on MITI. What do you think of CYCC or do you follow it??

It’s hard to pick one or two stocks. In a risky field like biotech, I would spread that across several companies.
There is one company we are seriously considering at the moment, we might add it during the coming weeks.

I hope the R788 data are as good as TASKi 1, but large trials tend to be less positive than smaller ones.

ohad