Corcept Therapeutics Inc. www.corcept.com
Dr. Joe Belanoff's bargain-priced Corcept Therapeutics (Nasdaq:CORT) tackles the single biggest dilemma in psychiatry today. Antipsychotic drugs do wonderful work healing and stabilizing people with mental problems, but their Achilles' Heel is their metabolic side effects associated with morbid obesity, arterial heart disease, stroke and Type 2 diabetes which affect millions of patients. Near term FDA's completion review of Corcept's first commercial drug CORLUX with orphan status to treat Cushing's syndrome is scheduled for a decision by Feb. 17, 2012. A Stanford lecturer and part -time practicing psychiatrist tries to be a CEO who manages for the long run in a short run world.
By Robert J. Flaherty
Balance Sheet as of June 30, 2011
Nasdaq Symbol : CORT
Recent Price: $2.90 Total Assets: $52.7 million
52-Week Price Range: $5.07-2.54 Cash : $52.2million
Shares Outstanding: 84.2 million Long-Term Debt: $0
Estimated Float: 50.8 million Shareholders' Equity: $48.9 million
Stock Market Cap: $244.2 million Book Value Per Share: $0.58
Average Daily Share Trading Volume (3 month average): 253,838 shares
As observers we are consumed by the continuing global financial panic with its volatile stock prices and often overlook the many entrepreneurs who dedicate most of their entire careers focusing on important unsolved medical conditions. This issue we spotlight Stanford University lecturer and part-time practicing psychiatrist Dr. Joseph K. Belanoff. As co-founder and CEO of Menlo Park, CA -based Corcept Therapeutics Inc. (Nasdaq:CORT-2.90) he tries to manage for the long run in today's short run world. Let us hope financial backers and investors will continue to support Corcept and other efforts they consider worthy and help conquer many of our present medical ills. It is thrilling that so many are trying.
This article will mainly focus on Corcept's unique effort to alleviate one of the most serious, least discussed and neglected health problems in America- the dilemma caused by antipsychotic drugs which effectively treat mental illness yet can cause unwanted side effects of obesity, diabetes and metabolic syndrome. "In my opinion the single biggest problem in psychiatry today is the enormous metabolic problems caused by taking these antipsychotic medications," says Dr. Belanoff of which excessive weight gain is one of the most serious and prevalent. "Antipsychotic drugs do wonderful work stabilizing mentally ill people but their Achilles Heel is side effects which cause new serious problems sometimes leading to a shorter life."
Obesity is often named the number one health problem in the U.S. because it can lead to other diseases and shorten life by decades. "Morbid obesity is one of the saddest topics in our field of mental health," continues Dr. Belanoff. "The median life expectancy of someone with chronic mental illness is somewhere between 50 and 55." That is about two decades below normal.
Yet a major contributor to this tragedy is seldom discussed. Using antipsychotic drugs can help restore normalcy to patients with mental illness, but associated weight gain can be rapid, substantial and long lasting. Sometimes patients' bodies blow up like balloons. Because a drug side effect is insulin resistance, once gained, the harmful extra weight is very difficult to take off. It can lead to many serious new health problems often with significant consequences.
In the U.S. alone, something like $16 billion antipsychotic drugs are sold annually to millions of patients. All of the following drugs cause weight gain in addition to other undesirable side effects and it is only a question of degree as to how much harm they cause. The drugs are olanzapine Zyprexa (Eli Lilly and Company), risperidone Risperdal (Johnson & Johnson), quetiapine Seroquel (AstraZeneca), clozapine Clozaril, (Novartis), ziprasidone Geodon (Pfizer) and aripiprazole Abilify (Bristol-Meyers Squibb.)
Dr. Belanoff is one of the many unknown entrepreneurs trying to change the world and do well for his company too. The good news is that Corcept Therapeutics hopes to do something to improve the lives of mental patients and ameliorate these harmful side effects with a commercial product. The bad news is Corcept will optimistically take at least 5 years and probably a few more to get solution into caregivers' hands.
For those who like bargains at $2.90 recently the stock of Corcept is down 43% from its 12 month high of $5.07 and 77% from its all time high of $12.65 back in 2004. Flaherty Financial News Newsletter wrote about Corcept Therapeutics Inc. (Nasdaq: CORT) in Dec. 2008 at $0.97 and its shares went to $5.07 before recently sharply correcting to $2.90. That is good for a gain of almost 200% but the stock can still do much better. Success in its endeavors should produce a gain of 50% to 100% within two years and longer term a new all time high in a normal stock market, which would be a gain of 336%.
On June 2011 the company made important progress with FDA acceptance of Corcept Therapeutics New Drug Application for its orphan drug CORLUX. This is its very first drug which it hopes will be approved by February 17, 2012 to treat Cushing's syndrome which affects 20,000 people and is also in Phase 3 trials to treat psychotic depression. "It is a big accomplishment for us," says Dr. Belancoff. "We're a little company but we had to walk through the same doors as Merck, Pfizer and Lilly."
If FDA approval of CORLUX is obtained, Corcept not will seek a partner at least in the U.S. to market and help bring in its first commercial revenues. This is because this orphan drug market is very concentrated and Corcept would like to keep 100% of the economic pie. Currently, with a current ratio of 13 to one Corcept is very liquid with over $52 million in cash. But it will need a few times that to achieve its ambitious long term goals.
Succeeding in Cushing's syndrome is the first step to achieve credibility and to create a lot of value in the others things Corcept is doing. Over the next five to seven years Corcept hopes to commercialize a next generation of specific cortisol receptor antagonists like CORT 108297 to prevent the weight gain and morbid obesity caused by antipsychotic drugs used by millions of mental patients. Assuming there were no revenues coming in from CORLUX which has yet to receive FDA approval and Corcept was developing CORT 108297 as a science project perhaps $150 million would be required.
Let's get technical to understand what Corcept is trying to do and why its effort is so special. Founded in l998 Corcept Therapeutics engages in the discovery and development of drugs for the treatment of severe metabolic and psychiatric disorders. It focuses on drugs for disorders associated with abnormalities in the body's regulation of the steroid hormone called cortisol.
All humans need cortisol to live. It puts sugar into the blood stream and gives you energy to handle daily problems. Sometimes called the "stress hormone", cortisol plays an important role in healthy individuals and helps them meet life's everyday challenges.
However, in excess or at irregular levels cortisol is implicated in a broad range of numerous metabolic and psychiatric illnesses with dire consequences. Disorders arise when you have an irregular flow of cortisol or if you have too much cortisol circulating throughout your body. Stanford University's Jerry Reaven was the first person in the U.S. to describe the metabolic syndrome contributing to such disorders as weight gain, excessive cortisol, arterial, stroke and tendency to Type 2 diabetes.
What can be done about this? Also known as mifepristone, CORLUX is the lead first generation compound in Corcept's development portfolio. It is a small molecule which blocks the cortisol (GR-II) receptor and blocks the receptor's activation by cortisol. That is why CORLUX is being evaluated by the FDA in Corcept's initial New Drug Application for the treatment of Cushing's syndrome and is in Phase 3 trials to treat psychotic depression, severe unmet needs in which excess or irregular cortisol plays a role. In Cushing's syndrome tumors create excessive cortisol with debilitating symptoms like diabetes mellitus, high blood pressure, weight gain, a rounded face, increased fat around the neck, severe fatigue, weak muscles, osteoporosis, skin changes, infections, poor quality of life, irritability and depression. Separately certain patients with psychotic depression suffer from abnormal cortisol activity and often increased cortisol levels. For dealing with both disorders Corcept hopes that the use of the cortisol blocking agent can provide better treatment for currently distressed patients.
In France Rouseel Uclaf discovered the active ingredient in CORLUX (mifepristone) in l980. Known for many years as "the abortion pill" because the compound blocks the progesterone receptor, mifepristone is still approved in the U.S. and internationally for the termination of early pregnancy. But it also blocks the cortisol (GR-II) receptor which was of far greater interest to researchers at Stanford University.
The composition of matter patents surrounding mifepristone expired in l998, and Stanford has developed new ones for different uses and applications. It is some of this intellectual property Corcept has licensed from Stanford to protect certain important methods of use for its initial drug CORLUX.
After receiving his undergraduate degree from Amherst and his medical degree from Columbia, Dr. Belanoff headed west. Besides being Corcept co- founder and CEO, this 54 year old has held various positions in the Department of Behavioral Sciences at Stanford University and is currently a clinical faculty member.
"I do two things at Stanford," explains Dr. Belanoff. "Actually I work clinic half a day a week, seeing some patients as a psychiatrist, mainly adult patients with mood disorders. Additionally, one quarter of every year, I teach a course to the residents. In the course just concluded I taught a review of psychopathology with the goal of helping the residents achieve a final synthesis of all that they learned so that they can be adequate to prepare for the work that they are going to take on after graduation. I love to do that. It really keeps up my skills."
As a co founder of Corcept Dr. Belanoff's psychiatric knowledge quickly came in handy. "We knew even at the very beginning that cortisol goes everywhere in the body and led to all sort of problems related to excess cortisol activity. We thought there would be several disorders where a cortisol receptor antagonist (blocker) could be useful. Early on an enormous one we thought about was antipsychotic drug induced weight gain."
Cortisol by itself puts sugar in your blood stream and affects your metabolism and how sensitive you are to insulin. It is not entirely understood how these drugs cause the excessive weight problem. The theory Dr. Belanoff ascribes to is that antipsychotic drugs cause insulin insensitivity. Additionally, appetite increases leading to increased caloric consumption and metabolism becomes more efficient at storing fat. Sedation of the patient also leads to decreased exercise resulting in less caloric expenditure. Even patients who eat the same amount of calories will actually gain weight. Dr. Belanoff believes a product blocking cortisol would increase insulin sensitivity and reverse some of the adverse side effects.
Because the side effects are so debilitating some patients adjust their medications so their dose is lower or go without it for a period but they are playing with fire. "People taking an antipsychotic medication need to take it!" stresses Dr. Belanoff. "It is a very unfortunate dilemma. At the same time patients are taking a medication that is necessary for their life, you are giving them side effects which can be very harmful."
Once on antipsychotic medications it is very hard to take the weight off. Many patients also do not always have the healthiest life style. Some smoke and their diet is poor. And sadly the medicine they have to take for their psychosis makes losing weight much harder. In many cases Dr. Belanoff believes frustrated doctors put too much blame for the weight gains on their patients while he believes most of it comes from the medications.
Short term Corcept has a lot of chips riding on a favorable FDA review of its very first product CORLUX. Success would give the company credibility and put it in a very different financial situation with a revenue stream. Then it can really gear up to go after the huge antipsychotic drug induced weight market.
Meanwhile, why not ask for funding from the antipsychotic drug makers who are causing this problem? Eli Lilly provided a grant of over $1 million so Corcept researched some key information but Corcept is cautious about requesting more. "At this early stage it is unwise to become too tied up with any one company when there are five with products which need to be improved for patient safety, " says Dr. Belanoff. "Besides it is too early. I don't think we are far enough along to make a good deal financially. First you really want to demonstrate these new compounds have efficacy and we don't know yet. We have a theory. It worked well in animals, but not everything in animals translates into people. So we are now in the process of doing the first Phase II studies in humans with our second generation drug CORT 108297. Initially we are going to treat healthy people but eventually we hope to expand this to treating patients.
"We never say never but we are planning to operate as a standalone company," continues Dr. Belanoff. "We have a lot left to accomplish on our own and we think that the programs within the company can really add a lot of value and it has not been recognized by the stock market."
Flaherty: "You mentioned your next generation?"
Belanoff: "The next generation of compounds will block the cortisol receptor but do not block the progesterone receptor. They will not have the side effect of termination of pregnancy or some other issues. They will be at a medical advantage because they will be more selective. Our CORT 108297 to treat weight gain induced by antipsychotic drugs really worked well in animals and is through Phase I which is safety. Now in the beginning of Phase II we are getting the first readouts for efficacy in 25 healthy patients. Phase III may involve 2,500. We have to take it step by step and not get ahead of ourselves."
Flaherty: "If you do create such a product do you think a lot of psychiatrists would prescribe it?"
Belanoff: "Certainly if you had a separate or embedded drug which mitigated antipsychotic drug induced weight gain that didn't create a whole lot of new side effects of its own, I think that new drug would be a very popular medication. Today clinicians know they are giving their patients a new problem even if they are dealing with the psychiatric symptoms. At this point in our profession it is one of our biggest issues. We have medicines which are effective for mental illness but create troubling side effects.
Flaherty: "Do you have any competition?
Belanoff: "We're not aware of any competition in cortisol receptor antagonists. Are there any others who will look at antipsychotic drug induced weight gain? Actually, I hope there are, but I am not aware of any."
Flaherty: "What are your biggest obstacles?"
Belanoff: "You have to raise the money; you have to have successful clinical drug trials; you have to have a successful trip through the FDA. All of those things are hard. Once you climb one mountain, you have to climb the next."
Flaherty: "It is so good to see a company like this staying on course. So often raiders come in, take over, strip their cash and assets and do not care about all the good things the company might have achieved long term."
Belanoff: "We have been very consistent, single minded in the way we develop things. We believe the medical need is very substantial and patients will really benefit if we can bring these things to fruition."
Flaherty:"Your time line to get a commercial medication to ameliorate the weight gain is five to seven years. It is a sad thing that millions of people will die in the meantime and I do not see a short term answer."
Belanoff: "You're absolutely right. What really preys on me is that while we are developing a medication people are suffering. But that is the real world."
Flaherty:"Progress takes time. In the meantime I really believe we are better off having the antipsychotic drugs even with their serious side effects than we were before when people had no choice but to go around hearing voices. These medications ARE effective antipsychotics. If you by using your company can reduce this metabolic Achilles Heel you would be doing your patients a great service. Trying to lessen harmful side effect is a satisfying way to spend your life."
Belanoff: "I am glad you brought that up. One of the really hard decisions for me was that I really enjoyed being a full time doctor. I like being in a room with patients. So for me to spend a lot of my time developing a drug means I can't spend that time being with patients. But I'm hoping in the end if we are successful a lot more patients than I could possibly see on my own will benefit."
Flaherty: "And that is the way it should be. You don't have to see everyone to help them. You get a special thrill when you are close up with people, but you will help millions you will never see if what Corcept is developing works out."
Belanoff: "That is my hope. I don't think the general public is really aware of how prevalent mental illness is and how the medications to treat patients create their own new problems. As a practicing psychiatrist I can tell you there is a need for improved medications because our patients are really suffering. We see it in the privacy of the doctor's office. These are our brothers, our sisters, our family members, our children, and there are millions of them!" -RJF
Corcept Therapeutics Inc.
149 Commonwealth Drive
Menlo Park, CA 94025