Replies to post #203165 on Biotech Values

[Titan V]

Dew, how do you think this will impact Opdivo NSCLC combination therapies? For instance, Heat Biologics has this trial using Opdivo for NSCLC.
http://ir.heatbio.com/press-releases/detail/525/heat-biologics-presents-a-poster-on-its-hs-110nivolumab

Would HTBX now be more attractive because of it's potential to increase Opdivo response rate in NSCLC?

[dewophile]

we will probably get a chance to see the data in pts with higher PD-1 expression since this was a prespecified endpoint.
This might down the road be water under the bridge if data on combo w chemo or other IO combos works out. The massive swings in valuation obviously show how much of BMY's market cap is tied to opdivo. with so many PD-1s in so many combinations who the hell knows how the commercial landscape will wind up - clearly risk here for those who are currently leaders (it's why crazy sums are paid like bmy's 800M for a preclinical compound from flexus)

[DFRAI]

Perhaps BMY needs a little ZIOP

In Preclinical studies IL12 + anti PD1 at 15mg results in 100% survival at day 80.

Controlled tumor IL-12 production was able to
stimulate the immune system in the presence of innate
tumor immunosuppression
• The addition of anti-PD-1 therapy resulted in a
reduction in tumor innate immunosuppression
• The combination of both therapies resulted in
decreased immunosuppression coupled with local
immunostimulation proved to be beneficial in the
treatment of glioma with a profound increase in
survival over controls & monotherapy
• Clinical study design to assess combination
therapy in recurrent GBM in progress

Ziop is starting phase 1 this year in combo above

http://ziopharm.com/content/02-pipeline/03-presentations-publications/3-asgct/1-regulated-expression-of-il-12-as-gene-therapy-concomitant-with-blockade-of-pd-1-for-treatment-of-glioma/asgct2016re.pdf

[DewDiligence]

More musings on CHECKMATE-026 trial/NYT write-up:

http://www.nytimes.com/2016/08/06/business/lung-cancer-drug-opdivo-fails-clinical-trial-to-expand-use.html

Not a bad synopsis, but author Andrew Pollack could have gone further by saying that Opdivo and Keytruda are very similar drugs (not merely members of the same class), and hence there’s no credible thesis for why Opdivo wouldn’t work well in first-line NSCLC among patients with sufficiently high PD-L1 expression.

Further, I don’t expect the economic harm to BMY from CHECKMATE-026 to be nearly as large as Pollack implies. We may presume that MRK’s Keytruda will soon be approved for monotherapy in first-line NSCLC for patents with >=50% PD-L1 expression, based on the results of the KEYNOTE-24 study (#msg-123339268). Hence, such patients are not going to use first-line chemo anymore, and third-party payers won’t be able to restrict such patients to cheap generic chemo regimens. Inasmuch as Opdivo and Keytruda have similar prices, payers won’t have any particular reason to oppose (off-label) Opdivo use in first-line NSCLC.

All told, in due course I foresee Opdivo and Keytruda dividing the NSCLC market roughly evenly rather than the lopsided win for Keytruda that some investors and analysts are now predicting.