Puma Biotechnology, which continues executing a very shrewd strategy of in-licensing promising/innovative candidates for further commercial development that have already tested out their technology through ongoing or completed initial clinical trials, has most recently garnered considerable attention for their initial foray, PB272 (oral Neratinib), both as a single agent and in combination with other drugs or chemotherapeutic agents for treating a variety of cancers.
The company held a conference call last month (Dec 17) to go over the ongoing Phase 2 and 3 clinical trial progress achieved in PB272, which is an extremely potent irreversible tyrosine kinase inhibitor focusing on the HER2 (human epidermal growth factor receptor 2) mutation, whose over-expression is typical among breast and other aggressive cancers, and which is strongly associated with both an increased recurrence rate of disease and poor prognosis. HER2 (or ERBB2, the gene in which the receptor tyrosine-protein kinase erbB-2 is encoded) has become an accepted biomarker standard for roughly 30% of breast cancer patients but the typical indication, approved drug Trastuzumab (Herceptin), is useful only in cases of HER2-positive individuals exhibiting over-expression and poses serious cardiotoxicity risks, not to mention the high cost of the drug. It is noteworthy here to point out that Journal of Clinical Oncology-published data from back in March of 2010, shows Phase 2 clinical trial work comparing Neratinib (as a single agent) and Trastuzumab in HER2+ metastatic breast cancer patients, clearly indicating that Neratinib was well tolerated, even by patients who had previously undergone Trastuzumab treatment.
Significant progress in HER2 mutated non-small cell lung cancer with PB272, as well as HER2-negative breast cancer patients with the HER2 mutation, adds significant weight to the report earlier last month (Dec 4) of top line results from the Phase 2 neoadjuvant treatment work done in breast cancer (I-SPY 2 TRIAL). I-SPY 2 essentially looked at Stage 2 (HER2-positive breast cancer) and higher women, to see how effective Neratinib could be in combination with standard chemotherapy in a neoadjuvant context and having graduated this unique trial, which is a collaborative effort from 20 major cancer research centers across the U.S. (as well as the FDA and major industry and foundation supporters), with statistically superior performance (Paclitaxel plus Neratinib versus Paclitaxel plus Trastuzuma), PBYI has been really starting to turn heads in the oncology space for their technology.
The recent conference call also gave PBYI a chance to look at their clinical trial progress in solid tumors that have an HER2 activating mutation (basket trial) and the broad-spectrum applicability evident in this open-label work further reinforces just how compelling their HER2 mutation-focused technology really is. The PBYI technology approach is more like Galena Biopharma’s (GALE) NeuVax technology, which uses the HER2-derived E75 peptide and immune adjuvant granulocyte macrophage colony stimulating factor to induce a targeted “killer” T cell assault on over-expressing cells, going right after root phenomena. In the case of PBYI, they are going straight after signal transduction through the epidermal growth factor receptors (EGFRs, for HER1 and HER4 as well). Efficacy in combination and as a standalone agent is abundantly clear from the clinical trial work and investors should take note of the potential for broad-spectrum Neratinib applicability in the oncology space as a driving factor for future performance of the stock.
2014 is shaping up to be a momentous year for PBYI, with Phase 2 or 3 trials across the board for their evolving pipeline. Investors should keep a close eye on the company for announcement of further results on Neratinib, with the Temsirolimus plus Neratinib trial in metastatic HER2-amplified (triple negative) breast cancer and the Neratinib plus Capecitabine vs Lapatinib plus Capecitabine trial in HER2+ metastatic breast cancer, likely occupying center stage.
To learn more about Puma Biotechnology, visit www.PumaBiotechnology.com
