Origins of an idea
But before the business model, there was an idea, one whose roots lay firmly in academic soil. In 1991, Alan Schatzberg,
a practicing psychiatrist who trained at Harvard, joined the faculty of the Stanford Medical School as chair of its Department
of Psychiatry and Behavioral Sciences, where he initiated a research project focused on the symptomatic biological origins
of episodic psychotic depression, a little understood subset of major depression, affecting about 15% of diagnosed patients.
Schatzberg was motivated by his early interest in the biological roots of mood disorders, which ran counter to the Freudian
sentiment among many in the profession that environment is determinative.
Plugging the Awareness Gap: Social Media Steps Up
In the course of this work, Schatzberg discovered a correlation between cortisol and cognitive changes in patients with depressive
psychosis, in which use of GR antagonists in test subjects led to a rapid improvement against delusional behavior. The fact
that improvement occurred in a short period of time—as little as a week—is significant, as psychotic depression differs from
other forms of mental illness by occurring in severe (suicide risk is high) but irregular bursts, after which there are long
intervals where the patient is lacking symptoms.
Schatzberg and his colleagues at the Medical School continued to investigate the cortisol link in areas ranging from drug
therapy to using imaging technology to identify stress responses in targeted areas of the brain. One volunteer was Belanoff,
an undergraduate English major who at age 29 left a trading desk job on Wall Street to go to Columbia University Medical School;
in 1992, he landed a residency in psychiatry at Stanford. "I was one of Schatzberg's first interviewees for a residency slot,"
relates Belanoff. "We hit it off after I told him I was specializing in psychiatry because we knew so little about how the
brain works—and even less about the drugs the profession prescribes: why, for example, do we see the biological impact of
a drug on mood or cognition in hours, while the broader clinical effects take weeks or even months? We can speculate, on an
empirical basis, but precise answers to that question remain elusive."
One of Schatzberg's drug targets was mifepristone, originally identified as RU-486 by Roussel-Uclaf, the now defunct French
company that developed it as a tool to induce abortions in women at risk in pregnancy. A synthetic steroid, mifepristone works
as a dual action drug with properties that combine to block the female hormone progesterone and prevent the absorption of
glucocorticoids in tissue and the bloodstream. The product was approved by the FDA in 2000 as an abortifacient for restricted
use, under physician supervision, during the first seven weeks of pregnancy.
Although the abortion tag received top billing, there was a steady trickle of interest in mifepristone's properties as a GR
antagonist, inhibiting the actions of cortisol on the brain and other major organs. Indeed, over the past 20 years, Schatzberg
and his collaborators produced several dozen peer-reviewed papers analyzing how GR antagonists like mifepristone work in these
areas. Given researchers' interest in the dual properties of the drug, the biological mechanisms behind mifepristone became
very well known, making it a top candidate for several different clinical indications.
Corcept's anti-cortisol platform
Early on, Belanoff began to see commercial potential in the intriguing scientific knot that cortisol presented to leading
academic researchers like Schatzberg. The work at Stanford in investigating links between GR antagonists and the control of
episodic psychotic depression had produced a substantial library of intellectual property, much of which was sitting on the
shelf. Belanoff, who by this time was looking beyond teaching at the Medical School and his private psychiatry practice, proposed
to Schatzberg, among others, to put his Wall Street background to use in creating a start-up company to pursue commercialization
of the cortisol research platform.
The first order was to go out and raise funds, and Belanoff developed a pitch for the Bay Area venture capital community focused
on the ways mifepristone and a few other compounds might be repurposed as an indication for the symptomatic relief of psychotic
depression, where there was no approved drug. Belanoff hit pay dirt with the local VC Sutter Hill Ventures—but only after
13 long interrogations led by ex-Syntex COO Jim Wilson, when the firm finally said it could no longer think of any reason
NOT to invest. Corcept Therapeutics was incorporated in May 1998 with Wilson as Chairman, Belanoff as CEO and Schatzberg as
a Board member (and passive shareholder). Employing a skeleton staff of 13, the company began working on two fronts: developing
a proof of concept and clinical study program specifically focused on mifepristone's use in psychotic depression; and compiling
an IP-protected library of selective GR antagonists—presently numbering more than 300, with mifepristone playing a central
galvanizing role. Sharing this knowledge asset in collaborations with leading researchers and other external academic experts
will also help Corcept improve the science and clinical understanding of how cortisol affects a wide range of diseases.
Despite this clarity of purpose, the hard reality is that Corcept spent 14 of its 16 years as a company without any marketed
product. Driving forward an approved indication on psychotic depression using mifepristone has yielded some modestly encouraging
trial results, but so far nothing is definitive and the trial has taken longer than expected—a pivotal Phase III trial involving
450 patients with a 1,200 mg dose of mifepristone is underway, with interim findings due at the end of the second quarter.
If the trial meets its endpoint—a measurable, rapid reduction in psychosis—the company intends to proceed with a new drug
application (NDA). The goal is to finally turn this indication into Corcept's second marketed product. Last December, the
company also announced it was filing an investigational new drug (IND) application for a Phase I study on mifepristone as
an indication for triple-negative breast cancer, its first foray into oncologics—and yet another specific condition lacking
any drug treatment.