Replies to post #122678 on Biotech Values

[NP1986]

I was referring to PF-0299804 earlier but mistakenly called it PF-804. I was under the impression that it is still in early or mid stage trials.

Anyway, in searching for updates on the PF-0299804 trials I came across some interesting preclinical data:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859699/?tool=pubmed

They suggest that resistance will arise against EGFR inhibitors that target T790M, unless they can inhibit T790M more potently. Do you recall from the Ariad presentations if '113 is a more potent inhibitor of EGFR T790M than the 2nd generation EGFR TKIs?

Speaking of '113, there is another molecule (WZ4002, Gatekeeper Pharmaceuticals) which targets EGFR T790M but not wild-type EGFR. However, its development is supposedly being held back due to a legal tangle over ownership rights.

I'm still quite conservative in my outlook for '113 in this indication, but I'm very curious to see how things pan out. Like you said, we still don't know if a lack of activity against wild-type EGFR is a negative or a positive.

[DewDiligence]

QGEN/PFE collaborate on KRAS companion diagnostic for dacomitinib:

http://finance.yahoo.com/news/QIAGEN-and-Pfizer-Partner-to-prnews-2730719686.html?x=0&.v=1

Dacomitinib (a/k/a PF-00299804) is PFE’s HER-1/2/4 inhibitor for NSCLC. It is in phase-3 trials in the first-line metastatic setting (for patients who received Tarceva in the adjuvant setting) and the second-line metastatic setting (for patients who received chemo in the first line); results are expected in 2012 and 2013, respectively:

http://www.clinicaltrials.gov/ct2/show/NCT01000025
http://www.clinicaltrials.gov/ct2/show/NCT01360554

Financial terms for the QGEN-PFE collaboration have not been disclosed.

[DewDiligence]

PFE’s Dacomitinib* fails two phase-3 studies in NSCLC; one trial ongoing:

http://finance.yahoo.com/news/pfizer-announces-top-line-results-120000873.html

Both trials evaluated dacomitinib in populations of previously treated patients with advanced NSCLC. The ARCHER 1009 trial, which included patients previously treated with chemotherapy (second/third line), did not meet its objective of demonstrating statistically significant improvement in progression-free survival (PFS) when compared with the EGFR inhibitor erlotinib.

Separately, the NCIC CTG BR.26 trial, which included patients with advanced NSCLC after standard therapy with both chemotherapy and an EGFR tyrosine kinase inhibitor had failed, did not meet its objective of prolonging overall survival (OS) versus placebo.

An ongoing, third Phase 3 trial, ARCHER 1050, is evaluating PFS of dacomitinib in a different patient population than was studied in ARCHER 1009 and BR26. ARCHER 1050 compares dacomitinib versus gefitinib in treatment-naïve (without prior treatment) patients with EGFR-mutant advanced NSCLC. The results are expected in 2015.

… Dacomitinib is an oral, once-daily, irreversible pan-HER (pan-human epidermal growth factor receptor) kinase inhibitor. Dacomitinib irreversibly inhibits the kinase activity of HER1/EGFR, HER2, and HER4 by binding covalently to the receptor tyrosine kinase domains and preventing autophosphorylation, thereby inhibiting downstream signaling and leading to tumor-growth inhibition and apoptosis.

*f/k/a PF-00299804.