Replies to post #182222 on Biotech Values

[iwfal]

ONTY

Failed cancer vaccines might live again with checkpoint inhibitors:

I have both been noting this repeatedly on an ONTY board (along with Ernie). But after watching Merck's decision processes with Stimuvax/Tecmotide (see my previous posts on this board) I am doubtful this happens with that drug. Perhaps with Provenge (another stellar decision making company) or with the bladder cancer immunotherapy? Maybe, perhaps, some checkpoint focused BP will have interest in ONTY's follow on (in theory a better version of Stimuvax) - but I doubt they even know that Stimuvax did well in the subgroup for which you expect it to do well (sMUC+).

All that said, still uncertain that there is useable synergy. Obvious thing to try but no guarantees.

[DewDiligence]

AMGN starts phase-1/2 trial of T-Vec + Keytruda in melanoma:

http://finance.yahoo.com/news/trial-initiated-evaluating-amgens-talimogene-212000967.html

The multicenter, open-label clinical trial is designed to evaluate the safety of talimogene laherparepvec [T-Vec] in combination with KEYTRUDA, as well as the efficacy of this combination versus KEYTRUDA alone and following progression after treatment with KEYTRUDA alone.

The study will be conducted in two phases:

• Phase 1 will determine the safety and tolerability of talimogene laherparepvec in combination with KEYTRUDA in patients with previously untreated, unresected, stage IIIB to IVM1c melanoma.

• The randomized phase will further evaluate the safety and efficacy of talimogene laherparepvec in combination with KEYTRUDA.

…The trial has enrolled its first patient and will evaluate the combination of these two therapies in approximately 110 patients across 35 clinical trial sites in the U.S., Australia and Europe.

The PDUFA date for T-Vec (monotherapy) is 7/28/15.

[iwfal]

Failed cancer vaccines might live again with checkpoint inhibitors:

Had some free search/thought time recently and I would suggest that I can understand why combos with vaccines haven't happened yet - because cancer vaccines have a horrible track record and even if you believe in them there is no way to know which would be potent enough to work well with your checkpoint inhibitor (actually I think the ONTY sMUC data for Stimuvax is likely to be real and at least moderately potent - but Merck KGA and ONTY have so effectively botched the analysis and decision making from the ph 3 that this is probably not widely known.)

What is more surprising to me is that no one is fired up to try combos with agents that are well accepted as having a primary mode of action through the immune system. ADCC. Rituximab, Trastuzimab and cetuximab are all well accepted to have as a primary part of their efficacy through ADCC (I.e. the immune system). See here.

There are now two slow rolling ph 1s in head and neck cancer doing combos of cetuximab with ipilimumab. And pidilizumab is running some trials with rituximab. But overall there is remarkably little interest. Not even much published preclinical work - but at least some of that published pre-clinical work is truly spectacular.

My guess as to why (and that tells on when it might turn around) is that:

A) although there is substantial data for ADCC being a potent MOA of these existing mabs it isn't how they are typically viewed. They (cetuximab etc) are viewed as being more like the TKIs.

B) so far the checkpoints have focused on diseases where these drugs don't generally apply (this, of course, ignores the fact that this may be an entree into the disease)

This, may, perhaps start to turn around with clinical data? E.g. I'd expect some readout of the first 2 or 3 cohorts of cetuximab and ipi at ASCO 2015.

BTW1 - an aging, but still valuable, summary of the PD-1s and their approach going forward is at http://www.onclive.com/_media/_pdf/Anti-PDL1_Immunotherapy2.pdf

BTW2 - there are two biotechs (Macrogenics and Xencor) publicly doing ADCC tuning and, hopefully, they will do a phase 1 combo with pd1 as their drugs get past ph1 monotherapy.