TEVA - The new CEO is not to blame for any of today's debacle but he is expected to get the company out of this mess...

TEVA— Schultz has officially entered his job yesterday, wonder how long will he last.

Re: "the weirdest set of combinations"

My first thought was that the motivation to combine drugs with one another is not always scientific and that PFE is combining already approved drugs they have or can use under an agreement.
Then, I thought they use sunitinib to provide a short-term effect, in which antiangiogenesis halts the tumor growth as it takes time for the immune system to kick in and provide a long-term effect.
After reading the paper below, I think I can see the scientific rationale behind that combination therapy: sunitinib downregulates myeloid-derived suppressor cells and tremelimumab activates T cells so together they might provide a synergistic effect to the vax. Kind of an educated fishing expedition :)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021055/

I didn't know that PFE was testing a prostate-cancer vaccine until you posted about it :)

I was more interested in "the weirdest set of combinations" as Peter called them, so read a couple of papers about that. Figuring the answer to your quiz was kind of intuitive and all I had to do was to google "Tremelimumab rights" to verify.

Re Quiz
When MedImmune (AZN subsidiary) has in-licensed tremelimumab back in 2011, Pfizer has retained the rights to use tremelimumab with specified types of combination therapies. In the study you cited, It is given to some patients as part of a possible regimen, with the vax booster (plasmid DNA) in hope that an anti CTLA-4 will further increase the immune response of the vaccine.

RDHL -13%

Another possible disappointing point from their PR:

TEVA - what a crash!

That's cause you're using the Hebrew calendar, Aaron :)

The negative effect on daily and thrice-weekly Copaxone will be stronger if a company like Mapi Pharma would succeed in bringing a monthly Copaxone Depot to the market (at least 3 years away for Mapi).

[OT/Yahoo portfolio tool]

[OT]—The "uk" workaround to pull up the old Yahoo portfolios is still working for me.

Apparently, AZN didn't count any BLA submitted by MedImmune even after the acquisition. Technically, MedImmune is the filler but as noted it is just a gimmick.

MedImmune Vaccines (formerly Aviron) has submitted the first BLA for FluMist and the following sBLAs also as a unit for AZN. Guess AZN wanted the headline of Its first BLA :)

If you search clinicaltrials.gov you'll find quite few combo trials in different tumor types also dosing ipi at 1 mg/kg. Think the optimal dose/schedule is not final yet but it will probably be tumor dependent.

No, not following AZN that close but someone who does mentioned this not so long ago :)

I-O MoAs

To put in a bit more scientific way: anti-CTLA-4 works in early-phase T-cell response (priming phase in the lymph nodes) and anti-PD-(L)1 affects the later stages of T-cell immune response (at the effector phase in the lymph nodes and tumor microenvironment).

PRGO - what a mess.

Sorry for just posting the website without checking. Yes, Immunoscore is an active project: their team leader has updated on their work last ASCO:

http://meetinglibrary.asco.org/content/168666-176

There are several publications you can find via pubmed.

Not a companion diagnostics but there's the immunoscore project developing a standardized assay to classify cancer patients based on their immune systems and could predict response to treatment:

http://www.immunoscore.org/index.shtml

Re: SGEN SGN-CD33A AML trial clinical hold
I assume that the full clinical hold was placed on transplant eligible patients as these patients are more vulnerable either pre or post ASCT.

After the last ASCO, I think that even ABBV people think they overpaid for Stemcentryx. Quite a tradition for big pharmas to overpay, isn't it?

Abbvie has through stemcentrx one of the first ADCs with this new PBD dimer-based payload in clinical trials - Rova-T (phase III, SCLC).

Btw, the link between SGEN and ABBV ADCs. is Spirogen.

Happy holidays!

SGEN SGN-CD33A AML trial clinical hold

It's either the “sink hypothesis” is wrong or they are missing something so it is not complete. But in any case, I think the “sink hypothesis” has been discredited by the latest Solanezumab data.

Solanezumab binds soluble a-beta. According to the "sink hypothesis" removing peripheral, soluble a-beta should impact the insoluble a-beta deposits in brain plaques, in order to maintain equilibrium between the two forms.

Re: Placebo effect

Hi Jeff, long time...

Your point is correct of course when it comes to humans (in the study I have linked to, researchers worked with mice). I am very curious to see further work done on the possible link between placebo effect and the immune system in humans.

Thanks for the kind words!

Semi OT
Apropos to placebo effect, an interesting basic study and really cool effect.
I have only parked the link and conclusions, not the full paper because I suspect it is of interest just for very few readers and they have access.

http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4133.html

BIIB -12% on phase-2 anti-LINGO results in MS

Wow, I thought there was little expectation that anti-LINGO-1 would succeed.