Puma Biotechnology, (NYSE:PBYI) is a $3.2 billion market cap company initially focused on developing tyrosine kinase inhibitor neratinib (PB272) for HER2 positive breast cancer. The company has conducted 11 clinical trials for its lead candidate, with over 2,000 patients contributing to a favorable risk-benefit profile, per inflection point clinical trial readouts over the past quarter. Oncologic Drugs Advisory Committee (ODAC) at FDA recently voted for approval of neratinib in HER2 positive extended adjuvant treatment of early stage breast cancer in May 2017. ODAC vote is not binding but carries strong weight in the decision-making process. Given FDA director Gottlieb's new aggressive policies regarding the slow and outdated drug approval process at FDA, this was seen by the market as a "sure thing". The company is advancing neratinib in discussions with EMA for European markets, with validation in August 2016. Other investigations include neratinib in combinatory therapy for metastatic breast cancer and in solid tumors as well.

Neratinib blocks signal cascades of epidermal growth factor receptors or EGFRs, specifically: HER1, HER2, HER3, and HER4. A number of studies are showing nice anti-tumor efficacy. Taken together with ODAC favor, Phase 3 result emphasis for neratinib which met primary endpoints appears to have led to the robust response in the market for high probability of FDA approval. Two-year disease-free survival showed a 2.4% improvement for neratinib versus placebo in ITT population. Five-year disease-free survival showed a 2.5% improvement. In HR+ patients, neratinib adjuvant therapy showed a two-year disease-free survival rate of 95.4% compared to 91.2% in placebo. Five-year disease-free survival conferred a 4.8% benefit. Two-year HR patients' disease-free survival showed a meaningful advantage, but five-year data was not statistically significant.

The company recently presented data June 3 at ASCO 2017 summarizing positive results of its Phase 2 trial in HER2-positive metastatic breast cancer that has metastasized to the brain. Nearly half of the patients in a neratinib plus chemotherapy cohort achieved a central nervous system (CNS) objective response with overall survival data remaining immature at 13.5 months (and counting). CNS progressions remain a huge comorbidity factor in patients with brain metastases. With the ability to cross the blood-brain barrier, and with diarrhea being the number one adverse event, PBYI is well-positioned to advance in this space with neratinib. Studies examining antidiarrheal prophylaxis (Loperamide) to reduce diarrhea severity during neratinib treatment have proven effective. Phase 3 data showed grade 3 diarrhea decreased from ~40% to ~31% with loperamide, to ~23% with loperamide and budesonide, and to 11.5% with loperamide and colestipol. Safety studies examining children and young adults with cancer are also ongoing.

Multiple studies are generating impressive cancer therapy data for neratinib, including clinical data presented at AACR on neratinib in the treatment of patients who have solid tumors with activating HER2 or HER3 mutations. Additional data was also presented on the combination of T-DM1 and neratinib in patients with HER2 positive metastatic breast cancer (MBC) that has previously been treated with pertuzumab and trastuzumab. The company has done extensive analysis of breast cancer NSABP FB-7 biomarker during neratinib treatment with a variety of immuno and chemotherapy regimens to qualify its objective tumor response. Mechanistically, phosphoHER2 levels and truncated HER2 mutants (p95HER2) demonstrated statistically significant higher levels in patients who achieved a pCR with neratinib than those treated with trastuzumab or trastuzumab plus neratinib who did not. Moreover, dual pathway suppression (HR/ER+ and EGFR/HER2+) has been seen only in neratinib and not in Herceptin and Tykerb (Novartis (NYSE:NVS)).

The company has listed other potential tissue types to expand its label for neratinib, including non-small cell lung cancer, colorectal cancer, and solid tumors (any HER2-associated tumors). Roche (OTCQX:RHHBY) annual sales for Herceptin (trastuzumab) approach $5 billion. In contrast, Tykerb has not fared as well due to its unfavorable toxicity profile, with sales in the hundreds of millions. The HER2 positive breast cancer market is estimated to be about $13 billion by 2023. Given this massive market and plenty of room to expand label into other high dollar indications, Puma may still have quite a bit of upside and is generally de-risked. It certainly becomes very attractive on any stock price pullbacks.

Puma reported at end of 1Q 2017 cash and cash equivalents of $105.1 million and marketable securities of $88.9 million, with a 1Q net loss of $72 million. Cash runway is expected to last through mid-2018, with a burn rate of approximately $35 million per quarter. If the company is forced to raise funds, it should be able to do so at a good market value, given the advanced stage of its drug development. Strong Bio recommends a watch list spot for the stock and manageable delays or setbacks as a potential buying opportunity. Moreover, it may be a takeover candidate and could undergo some downward volatility in the standard process of stop-loss triggering. Such swoons will probably not last long as market support should be strong. With market cap of $3 billion and potential market quite a bit larger, there is plenty of room for value position here if sales meet expectations.

Risks for the company to investors are primarily centered around its one-trick pony pipeline. But when the trick is good enough, it's going to bring bank. Its advantage in efficacy will certainly gain a reasonable stake in the market for those that can tolerate the adverse events. In fact, the adverse event of diarrhea is somewhat severe, but luckily, most of that risk was mediated with appropriate prophylaxis regimen. It perhaps would have contraindications for those with extreme inflammatory bowel or related disorders. FDA-related large scale manufacturing risks and regulatory hurdles could prove to add delays and pitfalls to Puma's terrain, and since this is the only revenue-maker in its pipeline, a lot hinges on its expeditious advancement. However, given the aggressive stance at FDA to get life-saving therapies available to patients, most regulatory risks are ameliorated. Partnership decisions will be important inflection points moving forward.

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