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Biotech / Medical : T/FIF Portfolio -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (803)	4/17/1999 3:30:00 PM
From: NeuroInvestment	Read Replies (2) \| Respond to of 1073

Rick: Have just started to occasionally look at the erudite discussions going on here and Biotech Valuation. FWIW, regarding NBIX's CRF antagonist, this is an excerpt from the NI Dec98 review of NBIX: "Anxiety: This is a key target for the CRF technology which is NBIX's hallmark. The Company has identified two types of CRF receptors (CRF-1 and CRF-2); a CRF binding protein (CRF-BP) which binds and inactivates CRF; and a subtype of CRF, urocortin, which appears to be active at CRF-2. CRF has both global and specific modulatory effects, based on the type of receptor and ligand involved, and their distribution in different functional areas of the brain. The hormonal effects of CRF involve the stimulation of pituitary gland processes that lead to the release of cortisol. This is integrally related to the ‘fight or flight response' seen in stressful situations, wherein sympathetic nervous system activity is upregulated, heart rate and blood pressure increased. Via both the release of cortisol and the stimulation of CRF receptors in the brain, the net result is an overall increase in arousal. This leads to the subjective experience of anxiety, and it has been noted that administering benzodiazepine anti-anxiety medications reduces the anxiogenic impact of CRF release in animal models. As we discussed in the September 1998 issue on anxiety, given the side effect and abuse potential of current anxiolytics, the modulation of anxiety-related CRF activity has become a desirable target for Neurocrine. This program has been partnered with Janssen, who spent some time wavering between depression and anxiety as the first target. Given the involvement of this neuroendocrine axis in 'fight-or- flight' hyperstimulation, we have always considered anxiety to be a more obvious target. There has been increased interest in the field in the application of CRF modulation to Post-Traumatic Stress Disorder (PTSD), a disorder wherein anxiety is ubiquitous, and depression frequent. Janssen has completed three Phase I safety trials totalling 80 patients; there does not appear to be any sedation, abuse, or tolerance, the compound's blood brain barrier access is good. Phase II studies in some subtypes of anxiety (PTSD and social phobia are possibilities) are likely to begin during 2H:99. Depression: Some patients with major depression have been noted to have heightened cortisol levels, inferring that heightened CRF levels accompany depression. The behavioral data for CRF effects in animals seems intuitively more consistent with agitated depression, wherein both anxiety and depression seem present, rather than with those depressive disorders wherein there is an overall suppression of activity. Since as many as half of all patients with major depression also have anxiety signs, Janssen in fact decided to start Phase II in depression first, a trial that just began in Germany. Ultimately, 40 patients will be enrolled in what will start as a dose-escalating study, then will utilize the single optimal dose (in the second half of the trial enrollees). This trial should be finished by mid-99. The decision to tackle depression first reflects Janssen's belief that depression is a larger market, and the fact that many of the researchers involved with this study specialize in depression treatment. We continue to suspect that CRF modulation will not be a treatment of choice in 'pure' depression or 'pure' anxiety; it might be a viable treatment strategy for disorders where both features coexist, such as in PTSD and agitated depression." NeuroInvestment (www.neuroinvestment.com)