Ok Pharma investors, here is the first part of a three part series that will cover Keryx’s (KERX) cancer drug Perifosine also known as KRX-0401. In Part-I, I’ll discuss how the drug is believed to work. In Part II and Part III, I’ll discuss the drug’s clinical trials, competitors, and chances for approval.

Ok so first off, what exactly is Perifosine?

This isn’t exactly the easiest question to answer because researchers still don’t fully understand the drug. So let’s take a look at how Keryx defines the drug:

“KRX-0401 (perifosine) is a novel, potentially first-in-class, oral anti-cancer agent that modulates Akt, and a number of other key signal transduction pathways, including the JNK and MAPK pathways, all of which are pathways associated with programmed cell death, cell growth, cell differentiation and cell survival.”

First, let’s pull up the diagram of the various signaling pathways (Akt, JNK, and MAPK, I am using a chart for a different diagnosis, but it includes all three pathways that we will be discussing, chart here) that we will be referring to. The diagram is helpful because it provides a visualized picture of what exactly a signal pathway is-don’t worry I’ll stay away from the scientific garble as usual.

What is a signaling pathway?

A signaling pathway is simply a pathway by which a cell converts one kind of signal or stimulus into another type of signal. Most processes of signaling involve an ordered sequence of biochemical reactions inside the cell, which are carried out by enzymes (an enzyme is simply a catalyst that causes chemical reactions in our body to keep us going) and are then activated by second messengers, resulting in a signal pathway. So looking at the chart, we can see where Akt (blue pathway), JNK (red pathway), and MAPK (yellow pathway) fit inside of a sample pathway.

What is Akt?

In simplest terms, Akt is a kinase enzyme (kinase means that it is a type of enzyme that transfers phosphate groups to other molecules) that plays a role in cellular survival. Akt is known to stop/inhibit cell death. It does this by inhibition or the stopping of the apoptotic (apoptotic is a fancy word for cell death) processes in a natural cell’s life cycle. How does it do this? Well, it is thought to do this by a process known as phosphorylation (phosphorylation means the addition of a phosphate to a group of molecules). The phosphorylation process turns off the components inside a cell that tell it to die, which then allows various cells to live. .

Why is this important in cancer patients? Well, Akt essentially stops cell death in Cancer Cells as well as normal cells, this then allows the cancer cells to survive and multiply. It is thought that cancer cells essentially highjack the Akt enzyme and its regulatory proteins in order to increase their ability to survive. Now here is the really tricky part, there is also evidence out there that suggests that Akt may also be responsible for suppressing cancer cells’ motility (motility simply means the ability to move around the body). In other words, it is thought that Akt can actually prevent the cancer cells from moving around the body. Why would this be important? Well if Akt can suppress a Cancer Cells’ ability to move around the body then it could also be a useful tool for stopping the spread of cancer. So here we have a double edge sword, at one end inhibiting Atk will cause a majority of Cancer Cells to die, but at the same time will actually allow some to run wilder in the human body.

What about the JNK and MAPK pathways that Keryx mentions?

Like Akt, the JNK and MAPK pathways are also believed to play a role in cell survival. Scientists generally believe that the MAPK pathway is an anti-apoptotic (stops cell death) pathway, which would help cancer cells survive because it helps reduce cell death. While on the other hand they think that the JNK pathway is a pro-apoptotic (promotes cell death) pathway, which would help cancer cells die. So in simple terms the two function are opposite of each other.

How does Perifosine fit into the picture?

In the simplest explanation, Perifosine inhibits Akt in the body, which then causes cell death (apoptosis) in the cancer cells essentially killing them off. Perifosine also inhibits the MAPK pathway and changes the balance between the MAPK and JNK pathways, thereby also inducing cell death (apoptosis) which then leads to the cancer cells dying off. Scientist however still don’t fully understand how the changes in these pathways work in the treatment of cancer, hence the clinical testing in multiple types of Akt inhibitors and different types of cancers.

Tomorrow I’ll discuss some of the clinical trials for Perifosine and go over some it’s competitors. For now, I hope the information was helpful to investors and if it was help out by clicking on some ads.