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In an age where only about 20% of drugs are FDA approved, drug development companies have the odds stacked against them. Therefore, they must develop a drug that is: 1) selective and 2) efficacious. In other words, the drug must target a cell of interest and produce an intended result. In oncology, a drug that targets and kills a cancer cell is highly desired. However, targeting and killing a cancer cell is only half the battle. The drug must also be given to the right patient. If not, the drug will not work no matter how selective and efficacious it might be. It is like giving an antitumor drug to a patient with the flu: the drug will not work.

Endocyte (NASDAQ:ECYT) is a drug development company that seeks to develop small molecule drug candidates (SMDCs) for cancer and other diseases. SMDCs like vintafolide (EC145) are drugs linked to targeting ligands. Targeting ligands are like keys. When they are inserted into the proper lock on a tumor cell, they selectively deliver antitumor compounds. Interestingly, ECYT also develops companion diagnostics in which it links an imaging agent to the same ligand to identify patients likely to respond its therapy. The imaging agent is like a flashlight. It illuminates the lock (tumor cell) to identify the patient as a candidate for drug therapy.

EC145 is ECYT's leading drug candidate in clinical development. EC145 is a vinca chemotherapy that targets the folate receptor (the lock) found on tumor cells. It preferentially kills tumor cells by disrupting cell division. In phase 2a clinical trials, EC145 demonstrated a favorable safety profile in ovarian cancer and non-small cell lung carcinoma (NSCLC). Using its companion diagnostic (Etarfolatide) in combination with EC145 resulted in a survival benefit to ovarian cancer patients whose cancers had folate receptor (compared to those who did not have folate receptor). Therefore, they were able to validate their drug approach in which they were able to identify patients who would respond to therapy.

According to ECYT, most cases of ovarian cancer (>85%) and NSCLC (>80%) are folate receptor positive. When you consider the incidence and mortality of both of these cancers, there is a highly unmet medical need: 22,240 women will be diagnosed with and more than half will die of ovarian cancer in 2013 alone; many more people will be diagnosed and die of NSCLC. Therefore, ECYT is attempting to address a large market, one it estimates at >1 million folate receptor positive cancer patients in the United States, Europe, and Japan, should EC145 prove efficacious.

In a phase 2b trial, platinum-resistant ovarian cancer patients were given EC145 in combination with pegylated liposomal doxorubicin (PLD). Compared to patients who received PLD only, those who received combination therapy had a longer progression-free survival (5.5 months vs 1.5 months). However, it is important to note that patients whose tumors expressed folate receptor (100%) did not demonstrate an overall survival benefit (hazard ratio 1.097). While the patients treated with combination therapy had, on average, an additional four months before the disease got worse, they ultimately died after the same period of time as patients treated with PLD only, indicating combination treatment did not improve survival outcome. Nonetheless, a phase 3 trial was started in platinum-resistant ovarian cancer patients who will be randomized to receive either EC145 and PLD or placebo and PLD. Results are expected in mid 2015.

Besides ovarian cancer, EC145 is also being pursued in NSCLC as a second line therapy or one used after first line treatment failure. However, its important to point out that a standard therapy (docetaxel) already exists to treat second line NSCLC, which could limit EC145's market penetrance. Thus, a phase 2b trial was recently started to compare EC145 and docetaxel in folate receptor positive (100%) NSCLC patients who failed one prior therapeutic regimen. Enrollment is complete and results are anticipated in 2014.

In the meantime, ECYT is also advancing EC0652 to better diagnose prostate cancer. EC0652 is an imaging agent, which targets prostate-specific membrane antigen found on malignant (and normal) prostate tissue. EC1719, an agent that combines tubulysin and PMSA, has demonstrated significant in vivo activity. Likely, these agents will be used in combination to identify and treat prostate cancer.

In addition, ECYT is developing EC1456 to overcome vintafolide resistance. In vitro and animal models using EC0531, which is an earlier version of EC1456, have demonstrated superior activity to EC146. ECYT is also developing EC1669 to treat autoimmune diseases characterized by inflammation like rheumatoid arthritis. EC1669 targets macrophages, which secrete pro-inflammatory molecules.

In combining a companion diagnostic that uses the same targeting ligand as its small molecule drug candidate, ECYT has a novel drug-diagnostic strategy that will enable identification of patients likely to respond to therapy. If its science were not enough to entice the biotech investor, one may not need to look further than the deal ECYT signed with Merck last year. According to terms of the agreement in which Merck gained worldwide rights to develop and commercialize EC145, Endocyte received $120 million in an upfront payment and is eligible to receive up to $880 million in milestone payments. While the milestone payments are far from guaranteed, the agreement makes ECYT financial viable. For the full year 2012, ECYT had an ending cash balance of $201.4 million enabling it to continue to develop its preclinical program.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company whose stock is mentioned in this article.

Source: 2 Are Better Than 1: Endocyte Uses Diagnostics To Complements Its Drugs