Biotech Values

[iwfal]

THLD - Comments on hypoxia, IO and THLD:

1) Having now listened to the last THLD, a brief summary of the TH-302 history:

a) Did great at pancreatic cancer PFS - both in ph 2 and ph 3. Just missed OS (p just barely above 0.05, although since it was a large trial the HR wasn't great). But the FDA rejected any attempt to file an NDA.

b) The Japanese subset of the pancreatic ph3 does, in fact, look reasonable - although I'd want to see the Japanese data from the ph2's and Japanese ancestry data from RoW to get good confirmation.

c) The other ph3, in sarcoma, completely failed (and, unlike the pancreatic which had an RCT for Ph2, the sarcoma ph2 was a comparison to historicals - it looked great compared to historicals! <g>). Note that THLD was running this trial, Merck was running the pancreatic - see my comments on THLD management.

2) THLD management was all about the post-hocs in the cc. I tend to avoid listening to conference calls of companies with this kind of ignorance, so it has been a while since I heard anything so annoying (e.g. they blamed the failure in osteosarcoma on the control group doing so well). This, of course, makes everything else they say suspect IMO.

3) As for the combo's with IO, the story that is told in the TH-302 literature (that I've found so far) is a little different than the story told by Curran in the XNCR presentation. In the XNCR presentation he talks of TH-302 providing "hypoxia ablation", but the TH-302 data is just about the drug being a hypoxia triggered pro-drug. See this Curran paper, for instance. I would think there is an important difference between "hypoxia ablation" and "drug killing the hypoxic core". Perhaps an evolution in understanding. Worth tracking IMO given the apparently strong data in models - but still very much a work in progress.

http://cancerres.aacrjournals.org/content/74/19_Supplement/629.short