Replies to post #2660 on Spectrum Pharmaceutecals Inc (SPPI)

[antihama]

Posi’s a WINNER for Exon 18 atypical P-loop mutations and osimertinib-resistance mutations (in addition to Exon20in). The first thing that stood out reading this abstract is that for 2nd Gen TKIs, of which pozi is one, the average inhibitory concentration (IC50) is 78 times greater than the average of 1st and 3rd Gen TKIs, and also that 2nd-Gen TKIs inhibited G719S/A-T790M mutations at concentrations 2-fold lower than third-generation TKIs. That’s pretty impressive. What’s more impressive is

Of the second-generation TKIs tested, poziotinib was the most potent for atypical exon 18 P-loop mutations; G719S/A-T790M mutations; and classical mutants with acquired osimertinib-resistance mutations (IC50= 0.4nM, 3.2nM, 0.8nM).

You might be saying “Ha, this data is in in-vitro pre-clinical studies, it’s not a predictor of what will happen in the clinic”. Well, you could have said that about the pozi exon 20 pre-clinical data too. As a reminder, the posi data at the 17th IASLC World Conf on Lung Cancer in Vienna Dec 4-7, 2016 showed per the PR

poziotinib significantly inhibited cell growth of all EGFR exon 20 insertions tested across the helix and loop regions with an average IC~50~ value of 2.9nM, as compared to osimertinib and rocilentinib (IC~50~ values =103nM and 850nM, respectively).

Similar type IC50s, right? Actually, the exon 18 IC50s are a little better! And we saw that the MDACC clinical data confirmed the in vitro data as a predictor of efficacy. So, I’m expecting good things from Zenith20 cohorts 6 and 7.

What else stood out is the # of patients that posi would be able to treat in these other cohorts. The abstract indicates 3.6% of exon 18 insertions are affected which is, low and behold, the same amount of ex20in lung cancer patients. There are 7700 exon 20 in NSCLC patients in the US (20,700 worldwide). Double these #s again if you use the basket trial population. I don’t have a handle on the # of osimertinib-resistance mutation patients that posi would be able to treat yet but I would surmise similar # s. Bottom line is, the patient population that posi will be able to treat is ever expanding and it’s just a matter of time till Wall Street sees that.