Targacept TRGT - 500 Beiträge pro Seite

[Erbse1]

Homepage: http://www.targacept.com/wt/page/company

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Recent Highlights:

Collaboration with AstraZeneca

• AstraZeneca continued to carry out its safety and product characterization studies of TC-1734 (AZD3480), Targacept’s product candidate for the treatment of Alzheimer’s disease and cognitive deficits in schizophrenia.

• Progressed the preclinical research collaboration designed to discover and develop additional compounds with pharmacological activity similar to TC-1734 (AZD3480) on course to meet or exceed established objectives for the first year.


Internal Product Development Pipeline

• Announced positive top line results of the Phase II clinical trial of mecamylamine hydrochloride as an augmentation therapy to citalopram hydrobromide, a treatment combination known as TRIDMAC™, for major depression.

• Conducted activities to support the planned initiation of a Phase II clinical trial of TC-2696, a product candidate for acute post-operative pain, in molar extraction patients by the end of the year.

• Filed a Clinical Trial Authorization application to initiate clinical development of TC-2216.

• Continued to advance the late preclinical product candidate TC-5619, a novel compound selective for the alpha7 NNR, toward the planned initiation of clinical development in 1H07.

Weitere Informationen: http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=116888520…

Schönen Tag noch
Erbse

[Erbse1]

Antwort auf Beitrag Nr.: 27.000.839 von Erbse1 am 18.01.07 05:04:35

Von der letzten Analystenkonferenz die Punkte, die für 2007 geplant sind.



Kurzer Kommentar des Börsenbriefes NeuroInvestor zu Targacept aus dem letzten Jahr:

Targacept: (from July 2006)

The AAMI trial for TC-1734/ispronicline (partnered with AstraZeneca ) produced better cognitive data than anyone had expected--Targacept included. Now AZ will develop it for Alzheimer's. They continue to seek a buyer for mecamylamine, which has been hanging in suspended animation for several years--other than producing about $1 million per year to Targacept in sales for Tourette's. They have other, unpartnered molecules nearing the clinic for pain and anxiety/depression, as well as TC-5619, which will probably end up optioned to AstraZeneca as well. With their IPO finally completed, albeit for less than they had sought, bringing in $45 million, they have the funds to move ahead.

[Erbse1]

Antwort auf Beitrag Nr.: 27.071.757 von Erbse1 am 21.01.07 06:55:16

Der erste Punkt aus der Liste ist abgehakt. Start von Phase 1 mit TC-2216. Nähere Informationen aus der Pressemeldung von Targacept. Bleibt abzuwarten, ob sich die vorklinische Ergebnisse dann auch bestätigen und die Hoffnungen sich erfüllen.


Targacept Initiates Phase I Clinical Trial of TC-2216

Winston-Salem, NC

January 08, 2007

Targacept, Inc. (Nasdaq: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics™, today announced that it has initiated a Phase I clinical trial of TC-2216, its product candidate for the treatment of depression and anxiety disorders.

The trial is designed to evaluate the safety and tolerability of TC-2216 and to assess its pharmacokinetic profile. The trial is a double-blind, placebo-controlled crossover study, with sequential ascending single oral doses administered to healthy male volunteers.


TC-2216 is a novel compound discovered using Targacept’s proprietary drug design platform known as Pentad™. The compound targets specific neuronal nicotinic receptors (NNRs), a class of receptors found in the central nervous system that play a critical role in regulating nervous system activity. TC-2216 selectively inhibits the alpha4beta2 NNR to modulate the release of neurotransmitters that are involved in mood regulation.

In preclinical studies, TC-2216 showed greater potency than and anti-depressant effects comparable to selective serotonin reuptake inhibitors and tricyclics, which are commonly used treatments for depression, as well as anxiety-relieving effects.

Targacept currently plans to develop TC-2216 as an oral monotherapy. In November, the company announced positive top line results from a Phase II clinical trial of TRIDMAC™, a treatment combination comprised of mecamylamine hydrochloride as an augmentation therapy to citalopram hydrobromide, in patients who did not respond adequately to citalopram alone. Mecamylamine hydrochloride binds non-selectively to various NNR subtypes, but there is a body of scientific evidence that suggests that its anti-depressant activity is derived through its antagonism at the alpha4beta2 NNR.

“Depression is a highly debilitating illness, and millions of people who suffer with it are not gaining adequate relief from existing therapies,” said J. Donald deBethizy, Ph.D., Targacept’s President and Chief Executive Officer. “The results of our TRIDMAC trial not only substantiate the promise of the NNR mechanism in the treatment of depression and other mood disorders, but also further bolster our enthusiasm for the potential of TC-2216.”

[Erbse1]

2006 and Recent Highlights:

Collaboration with AstraZeneca

- Determination by AstraZeneca ahead of schedule to proceed with
development of AZD3480 (TC-1734), a partial agonist at the alpha4beta2
NNR, in Alzheimer's disease and cognitive deficits in schizophrenia.
- Received a $20 million milestone payment from AstraZeneca.
- Met or exceeded established objectives for the first year of the
preclinical research collaboration with AstraZeneca designed to
discover and develop additional compounds with pharmacological activity
similar to AZD3480 (TC-1734).

Product Development Pipeline

- Announced positive results from a Phase II clinical trial of AZD3480
(TC-1734) conducted in age associated memory impairment. In the trial,
AZD3480 (TC-1734) achieved statistically significant results in the
50mg dose group on all three co-primary endpoints and was generally
well tolerated as compared to placebo. The Phase II AAMI trial was
initiated prior to the commencement of the collaboration with
AstraZeneca and was completed independently by Targacept.
- Announced positive top line results of the Phase II clinical trial of
mecamylamine hydrochloride as an augmentation therapy to citalopram
hydrobromide, a treatment combination known as TRIDMAC(TM), for major
depression.
- Initiated a Phase II clinical trial of TC-2696, an agonist at the
alpha4beta2 NNR and a product candidate for acute post-operative pain,
in third molar extraction patients in December 2006.
- Initiated a Phase I clinical trial of TC-2216, an antagonist at the
alpha4beta2 NNR and a product candidate for depression and anxiety
disorders, in January 2007.
- Continued to advance the late preclinical product candidate TC-5619, an
agonist at the alpha7 NNR, toward the planned initiation of clinical
development in 1H07.

Corporate Developments

- Completed an initial public offering of 5.0 million shares of common
stock at $9.00 per share in April 2006, resulting in $45.0 million in
gross proceeds.
- Added to an extensive patent portfolio of more than 85 issued or
pending U.S. patents, including in particular a composition of matter
patent for TC-2696 and a pharmaceutical composition patent for TC-5214,
an enantiomer of mecamylamine hydrochloride and a preclinical product
candidate.
- Hosted an NNR analyst day in December 2006 during which Targacept
scientists and other leading NNR researchers, as well as a
representative from AstraZeneca, spoke on developments and potential
therapeutic applications in the NNR field.
- Added Alan W. Dunton, M.D., a seasoned pharmaceutical executive with
considerable product development experience, to the board of directors.

[Erbse1]

Antwort auf Beitrag Nr.: 27.930.249 von Erbse1 am 23.02.07 18:16:18

Effect of ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI).
Dunbar GC, Inglis F, Kuchibhatla R, Sharma T, Tomlinson M, Wamsley J.
Clinical Development and Regulatory Affairs, Targacept Inc., Winston Salem, USA.

Cognitive decline seen in the normal elderly is associated with selective loss of neuronal nicotinic acetylcholine receptors (nAChRs). Nicotine given either by inhalation or transdermally helps cognition, but unacceptable side effects limit its utility. The present study assessed the safety, tolerability and effect on cognition of ispronicline, a highly selective partial agonist at the 4beta2 nAChR, in elderly subjects (n =76) with age associated memory impairment (AAMI). This double-blind, placebo-controlled cross-over study explored ascending oral doses of ispronicline in the range 50-150mg given as a single morning dose for a period of 3 weeks. Pharmacokinetics (PK) were assessed, as well as cognitive function measured by means of the Cognitive Drug Research (CDR) computerized test battery. Ispronicline had a favourable safety profile and was well tolerated at doses below 150mg. No effect of clinical importance was seen on biochemistry, haematology, urine analysis, vital signs, electrocardiogram (ECG) or Holter monitoring. The most frequent drug induced adverse event was light-headedness (dizziness). A beneficial effect was seen on cognition across the dose range. This was most marked at 50mg on factors measuring attention and episodic memory. PK analysis indicated a plasma Cmax range of 5-25/35ng/ml ispronicline was associated with the most beneficial effect.
These early results demonstrate ispronicline was well tolerated and did not display the side effects typical of nicotine. Ispronicline also had a beneficial effect on cognition in subjects with AAMI. This was seen most strongly in a Cmax range that had been predicted from pre-clinical animal studies.

[Erbse1]

Update Targacept 23.03.07

Our lead product candidate is a novel small molecule that we have historically referred to as TC-1734 and that our strategic collaborator, AstraZeneca, refers to as AZD3480. In December 2005, we entered into a collaborative research and license agreement with AstraZeneca AB for the development and worldwide commercialization of AZD3480 (TC-1734) as a treatment for Alzheimer's disease, cognitive deficits in schizophrenia and potentially other conditions characterized by cognitive impairment such as ADHD, AAMI and MCI. We currently expect that AstraZeneca will initiate two Phase II clinical trials of AZD3480 (TC-1734) in mid-2007, one in mild to moderate Alzheimer's disease and one in cognitive deficits in schizophrenia, and that both trials will be completed by the end of 2008.

Our most advanced product candidates, in addition to AZD3480 (TC-1734), are described below.

• TC-2216.
TC-2216 is a product candidate that we are developing as a monotherapy for depression and anxiety disorders. We are currently conducting Phase I single rising dose clinical trial of TC-2216 to evaluate its safety and tolerability and to assess its pharmacokinetic profile in healthy volunteers.

• Mecamylamine hydrochloride and TC-5214.
In 2006, we completed a Phase II clinical trial of mecamylamine hydrochloride as an augmentation treatment to citalopram hydrobromide, a commonly prescribed treatment for depression marketed as Celexa in the United States, for major depression. We refer to this treatment combination as TRIDMAC. Mecamylamine hydrochloride is the active ingredient in Inversine, our only product approved by the U.S. Food and Drug Administration, or FDA, for marketing. TC-5214 is one of the enantiomers of mecamylamine hydrochloride. We have not yet conducted a clinical trial of TC-5214, but expect that we will elect to advance TC-5214 into clinical development as an augmentation treatment for major depression in lieu of further development of mecamylamine hydrochloride.

• TC-2696.
TC-2696 is a product candidate that we are developing currently as a treatment for acute post-operative pain. We are conducting an ongoing Phase II clinical trial of TC-2696 to assess its pain relieving effects in third molar extraction patients.

• TC-5619.
TC-5619 is a preclinical product candidate selective for the †7 NNR. We believe compounds that selectively target the †7 NNR may have application in the treatment of conditions such as schizophrenia, cognitive impairment and inflammation. We are currently conducting additional preclinical studies necessary to support a regulatory filing planned for the second quarter of 2007 to initiate clinical development of TC-5619.

• TC-6499.
TC-6499 is a preclinical product candidate that we are developing currently as a treatment for one or more classes of pain. We are currently conducting manufacturing activities necessary to support the initiation of clinical development of this product candidate.


Source:http://biz.yahoo.com/e/070322/trgt10-k.html

[Erbse1]

Antwort auf Beitrag Nr.: 28.445.082 von Erbse1 am 23.03.07 09:00:27

[Erbse1]

TC-6499 is a novel small molecule that we are developing currently as an oral treatment for one or more classes of pain. TC-6499 modulates the activity of the α4ß2 NNR. In our preclinical animal studies, this product candidate demonstrated pain-relieving activity in multiple models of neuropathic pain, and we are evaluating its activity in additional preclinical models of acute and chronic pain. We are also evaluating TC-6499 as a potential product candidate to promote wakefulness instead of or in addition to pain.

[Erbse1]

Targacept "buy"

Monday, April 02, 2007 8:29:31 AM ET
Lazard Capital Markets

NEW YORK, April 2 (newratings.com) - Analysts at Lazard Capital maintain their "buy" rating on Targacept (ticker: TRGT). The 12-month target price is set to $14.
In a research note published on March 30, the analysts mention that the company has released limited details of the Phase IIb trials for the AZD3480 compound for AD and CDS, which were broadly in-line with the estimates. The analysts expect AstraZeneca to initiate the Phase IIb trials for AZD3480 in mid-2007 and announce the results by 2008. The trial initiation and results are expected to act as catalysts for the company’s share price, Lazard Capital adds.

[Erbse1]

Targacept Konferenz 11.04.2007 mit aktueller Slide-Show:
http://www.erbse.vm-elsig.de/1033_targa/

Pipeline klinisch:


Pipeline vorklinisch

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Targacept files $75 mln common stock shelf offer

WASHINGTON, May 25 (Reuters) - Targacept Inc. (TRGT.O: Quote, Profile , Research), a clinical-stage biopharmaceutical company, said on Friday it may periodically sell up to $75 million in common stock.

It plans to use the proceeds to fund operations and for general corporate purposes, such as working capital, development of clinical and preclinical product candidates, intellectual property protection and enforcement, capital spending, investments and acquisitions.

Under a shelf registration filed with the U.S. Securities and Exchange Commission, a company may sell securities in one or more separate offerings with the size, price and terms to be determined at the time of sale.

Kommt jetzt etwas überraschend. Dachte sie hätten erstmal genug Kapital für die nächsten zwei Jahre. Eine volle Pipeline zu entwickeln, kostet auch viel Geld. Ich denke mal, damit läuft der Kurs in nächster Zeit nicht so schnell davon.
Grüße
Erbse

[Erbse1]

Abstrakt zu TC-1734

Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers.

Dunbar G, Boeijinga PH, Demazières A, Cisterni C, Kuchibhatla R, Wesnes K, Luthringer R.
TARGACEPT Inc., 200 East First Street Suite 300, Winston-Salem, NC 27101-4165, USA.

OBJECTIVES: The aim of this study was to get insight into the central effects of TC-1734 (renamed AZD3480), a selective agonist at the neuronal nicotinic receptor of the alpha4beta2 subtype. MATERIALS AND METHODS: Electroencephalography (EEG) techniques and computerized cognitive tests were performed in young, healthy male volunteers during two double-blind and placebo-controlled studies: a rising single dose crossover study (from 2 to 320 mg) and a rising repeated dose study with a parallel group design (50, 100, and 200 mg). RESULTS: In contrast to acute administration, administration of AZD3480 over 10 days produced statistically significant enhancement of several cognitive measures (attention and episodic memory) compared to placebo. Regarding EEG data, AZD3480 showed acceleration of the alpha centroid and of the alpha peak in the single-dose study. This EEG profile of the acceleration type was confirmed in the repeated dose study on both day 1 and day 10, with the greatest effect observed with the highest dose. The EEG pattern shown for AZD3480 was consistent with that previously described with other drugs known to improve attention and vigilance (including nicotine). In addition, subjects dosed with AZD3480 showed a statistically significant increase in mismatch negativity (MMN) amplitude at 50 and 200 mg while reducing MMN latency (200 mg only), suggesting an improvement of pre-attentional mechanisms. CONCLUSION: These early data in healthy subjects provide encouragement to consider development of AZD3480 as a novel agent for the treatment of cognitive decline in the elderly, including age-associated memory impairment and/or dementia of the Alzheimer's type.

PMID: 17225162 [PubMed - indexed for MEDLINE]

[Erbse1]

Researchers Light Up for Nicotine, the Wonder Drug

Marty Graham 06.20.07

Smoking may be bad for you, but researchers and biotech companies are quietly developing pharmaceuticals that are decidedly good for brains, bowels, blood vessels and even immune systems -- and they're inspired by tobacco's deadly active ingredient: nicotine.

Nicotine acts on the acetylcholine receptors in the brain, stimulating and regulating the release of a slew of brain chemicals, including seratonin, dopamine and norepinephrine. Not surprisingly, the first scientific work that identified these chemicals and how they affect the body came out of nicotine research -- much of it performed by tobacco companies.

Now drugs derived from nicotine and the research on nicotine receptors are in clinical trials for everything from helping to heal wounds, to depression, schizophrenia, Alzheimer's, Tourette Syndrome, ADHD, anger management and anxiety.

"Nicotine is highly stigmatized -- and for good reason, because the delivery system is so deadly," says Don deBethizy, CEO of Targacept. "But the drug itself and the research generated by studying its effects on the brain both show great promise for helping us improve our physical and mental health."

DeBethizy worked for R.J. Reynolds Tobacco Company for 15 years -- he was one of the first to publicly declare that tobacco is addictive -- before he spun Targacept off as a separate company. RJR retains a 4 percent share of the Winston Salem biotech, which has one mission: to develop drugs that target the so-called "nicotinic receptors" in the human central-nervous system.

Nicotine performs that function to an unhealthy extreme. "Nicotine itself is hugely potent and not specific enough," says Linda Gretton, Targacept's director of communications. "But the research we have allows us to take the best therapeutic qualities of nicotine and develop treatments that target receptors."

With funding from pharma giant AstraZeneca, Targacept is headed into Phase II clinical trials for a compound that could help overcome cognitive deficits in people who have Alzheimer's or schizophrenia. The company is also in Phase I trials for a compound that treats pain from molar extractions. The drugs both resemble nicotine in their molecular makeup, but are missing nicotine's addictive properties and toxicity.

Research into the medicinal qualities of nicotine was spurred in the 1990s by the availability of nicotine skin patches. For the first time clinical researchers had a form of nicotine that would deliver a reliable dose for study, and could be paired with placebos in blind trials.

Patients suffering from ulcerative colitis -- a bowel disease -- were subjects of some of the first studies, following observations of unusually low rates of smoking among those with the condition. A 1982 article in the British medical journal The Lancet was titled, "Non-smoking: a feature of ulcerative colitis." Researchers subsequently found that the nicotine in cigarette smoke reduced occurrences of ulcerative colitis, though the drug wasn't an ideal treatment.

"It was somewhat effective, but as a long-term treatment it has its drawbacks, systematic side effects and difficulty administering effective doses," says Dr. William Sandborn, of the Mayo Clinic. "Still, there was a time that we had patients using nicotine patches as off-label therapy."

More nicotine surprises followed. In 2000, Stanford researchers who set out to prove that nicotine damages blood vessels found just the opposite: it prompts the growth of new blood vessels. "It may be the reason smokers' cancers are so aggressive, says Dr. Scott Harkonen, CEO of drugmaker CoMentis. "But it also raises the question: where would you want to promote new blood-vessel growth?"

The answer, it turns out, was found in diabetes patients, who too often lose a lower extremity to amputation after a wound becomes gangrenous -- a result of poor blood circulation. Rates of amputations have steadily increased, Harkonen says, and nicotine could be a key to reversing that trend. Now CoMentis is in Phase II studies for "a gel that contains nicotine that's applied directly to the wound site," says Harkonen.

CoMentis is also working with a European company to study the effects of nicotine on the immune system, where it seems to quiet immune responses that go haywire with certain immune disorders.

None of the nicotine-based drugs and molecular siblings have yet come to market, and the stigma attached to nicotine may cause patients to recoil. But "the idea of nicotine-based drugs is alive and well," says the Mayo Clinic's Sandborn, a gastroenterologist who's watching from the wings. "There aren't any approved drugs yet, but I believe they're coming."

"There will be a variety of nicotine-based drugs coming out," agrees Ed Levin, a nicotine researcher at Duke University, who's done groundbreaking research on improving mental function in schizophrenia, Alzheimer's patients and people with ADHA. Levin believes the drugs are something to look forward to.

"There will be great progress when the nicotine sister drugs come to market," he says. "About half the cigarettes in this country are bought by people with psychiatric problems -- high percentages of people with depression and schizophrenia smoke, for example.

"When we can give people their medicine in a form that doesn't kill them, it will be real progress."

[Erbse1]

Neuroprotective effect of nicotine on dopaminergic neurons by anti-inflammatory action.

Park HJ, Lee PH, Ahn YW, Choi YJ, Lee G, Lee DY, Chung ES, Jin BK.
Department of Neurology, Ajou University School of Medicine, Suwon, Korea.

Epidemiological studies have reported that smoking is associated with a lower incidence of Parkinson's disease (PD), leading to theories that smoking in general and nicotine in particular might be neuroprotective. Recent studies suggested cholinergic anti-inflammatory pathway-regulating microglial activation through alpha7 nicotinic receptors. In the present study, we used lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation models to investigate whether nicotine has a protective effect on the dopaminergic system through an anti-inflammatory mechanism. Nicotine pretreatment considerably decreased microglial activation with significant reduction of tumour necrosis factor (TNF)-alpha mRNA expression and TNF-alpha release induced by LPS stimulation. In co-cultures of microglia and mesencephalic neurons, nicotine pretreatment significantly decreased the loss of tyrosine hydroxylase-immunopositive (TH-ip) cells, approximately twice more than the LPS-only treatment. alpha-Bungarotoxin, an alpha7 nicotinic acetylcholine receptor subunit-selective blocker, considerably blocked the inhibitory effects of nicotine on microglial activation and TH-ip neuronal loss. Chronic nicotine pretreatment in rats showed that TH-ip neuronal loss induced by LPS stimulation in the substantia nigra was dramatically decreased, which was clearly accompanied by a reduction in the formation of TNF-alpha. The present study demonstrated that nicotine has a neuroprotective effect on dopaminergic neurons via an anti-inflammatory mechanism mediated by the modulation of microglial activation. Along with various neuroprotective effects of nicotine, the anti-inflammatory mechanism of nicotine could have a major therapeutic implication in the preventive treatment of PD.

PMID: 17581257 [PubMed - as supplied by publisher]

[Erbse1]

Evidence for a role of nicotinic acetylcholine receptors in schizophrenia.
Adams CE, Stevens KE.
Department of Psychiatry, Veterans Affairs Medical Center, Denver, CO 80220, USA. [e-mail]

Schizophrenia is a debilitating, complex and costly illness affecting roughly 1% of the world's inhabitants. The excessive degree of cigarette smoking exhibited by schizophrenic patients suggests that they might be self-medicating to ameliorate certain aspects of the characteristic positive, negative and cognitive symptoms associated with the disease. Morphological examinations found alterations in nicotinic receptors in postmortem tissue from schizophrenic individuals compared to controls, especially in the a7 and a4b2 subtypes. These data were consistent with molecular biology studies which demonstrated associations between polymorphisms in gene coding for these receptors and schizophrenia. In studies of nicotinic receptor stimulation in schizophrenia patients, improvement in sensory inhibition and cognitive deficits were observed following treatment, though the effects were transient. These results have spurred the development of new pharmaceuticals specifically designed to modulate nicotinic receptor function. The initial results from clinical trials of these new drugs appear promising, potentially opening new avenues of treatment for this devastating disease.

PMID: 17485411 [PubMed - indexed for MEDLINE]

[Erbse1]

Targacept Announces Initiation of Phase IIb Development of AZD3480 (TC-1734) for Alzheimer's Disease
Monday July 23, 8:55 am ET


WINSTON-SALEM, N.C.--(BUSINESS WIRE)--Targacept, Inc. (NASDAQ: TRGT - News), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics(TM), today announced that its strategic collaborator AstraZeneca has initiated a Phase IIb clinical trial of AZD3480 (TC-1734) in Alzheimer's disease. AZD3480, Targacept's lead product candidate, acts selectively on neuronal nicotinic receptors and has been evaluated in 12 clinical trials in approximately 540 subjects. In a previous Phase IIb clinical trial conducted by Targacept in age associated memory impairment, AZD3480 achieved statistically significant results on all of the primary endpoints, demonstrating cognitive enhancing effects in memory-impaired older adults.

The Alzheimer's disease trial is a double blind, placebo controlled study being conducted at sites in Western Europe, Eastern Europe and Canada. The trial design provides for approximately 500 patients with mild to moderate Alzheimer's disease to be randomly assigned to one of three dose groups of AZD3480, to an active comparator or to placebo and to be dosed over a 12-week period. The trial is expected to complete by the end of 2008. AstraZeneca is also scheduled to begin dosing in a Phase IIb trial of AZD3480 in cognitive deficits in schizophrenia in August 2007.

"We are very pleased with the planning and preparatory work conducted by our AstraZeneca colleagues to launch this important study," said J. Donald deBethizy, Ph.D., President and Chief Executive Officer of Targacept. "The resources that are being invested in this program clearly demonstrate the commitment by AstraZeneca to the broad development of AZD3480 in areas where the medical need is evident."

Bob Holland, Vice President and Head of the Neuroscience Therapy Area, AstraZeneca, added, "We are committed to developing innovative therapies for Alzheimer's disease and other cognitive disorders and are enthusiastic about the profile and potential of AZD3480. We believe that the scientific rationale and clinical results to date bode well for the potential of AZD3480 (TC-1734) to make a real difference in the lives of those suffering from Alzheimer's disease and their caregivers."

Alzheimer's disease is a progressive, degenerative disorder that attacks the brain's nerve cells, or neurons, resulting in loss of memory, thinking and language skills, and behavioral changes. Approximately 26 million people worldwide suffer from Alzheimer's disease. In the United States, Alzheimer's disease is estimated to affect more than five million people and the number of people age 65 and over afflicted with the disease is projected to increase by more than 50 percent to 7.7 million by 2030. Current treatment options have limited efficacy and significant side effects in many patients.

[Erbse1]

Targacept Presents Data from TRIDMAC(TM) Trial Showing Positive Effects of Mecamylamine as Augmentation Treatment for Depressed Patients
Jul 24 2007, 4:05 PM EST
Business Wire


Targacept, Inc. (NASDAQ: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics(TM), today presented positive research findings at the 2007 Summer Meeting of the British Association for Psychopharmacology (BAP). The data suggest that an add-on treatment of mecamylamine hydrochloride, a broad spectrum nicotinic antagonist, improved symptoms of depression in patients who were inadequate responders to first-line citalopram therapy.

"NNR antagonists like mecamylamine may be an important new therapy for treating this group of depressed patients with high unmet medical need," said Geoffrey C. Dunbar, M.D., Vice President of Clinical Development and Regulatory Affairs at Targacept. "The promise of the NNR mechanism as augmentation is particularly encouraging in light of the STAR*D study, which found that less than a third of patients became symptom free with first-line citalopram therapy." Dunbar also noted that per the Sheehan Irritability Scale (SIS), the data showed a statistically strong advantage in the improvement of irritability, which is a common feature of depression. The SIS is a clinical rating scale used to assess the extent to which emotional symptoms such as irritability, frustration, edginess, moodiness, anger with self, anger with others, and temper are present.

Mecamylamine represents a new class of promising antidepressant medications that target the brain's neuronal nicotinic receptors (NNRs). Targacept's depression program also includes TC-5214, one of the enantiomers of mecamylamine hydrochloride and a preclinical product candidate as an augmentation therapy, and TC-2216, a product candidate as a monotherapy for depression and anxiety disorders that is currently in an ongoing Phase I clinical trial.

The Sequenced Treatment Alternatives to Relieve Depression study, or STAR*D, funded by the National Institute of Mental Health (NIMH) was the nation's largest study of treatment-resistant depression. According to the NIMH, if a patient does not respond to a particular treatment, his or her options generally consist of trying an augmentation therapy or switching to another medication. Currently, there are no approved augmentation therapies for depression.

The Targacept study included an open label citalopram hydrobromide phase and a subsequent double blind, placebo controlled phase in which the effects of mecamylamine taken with citalopram, a treatment combination known as TRIDMAC(TM), were evaluated in patients who did not respond adequately to citalopram alone. In the trial, the treatment combination of mecamylamine and citalopram was generally well tolerated. Also, patients showed greater improvement on symptoms of depression and irritability when augmented with mecamylamine, as compared to placebo. Patients for the trial were recruited from nine outpatient facilities, one in the U.S. and eight in India. Of the 472 subjects screened, 450 entered the trial and 192 were randomized to double blind medication.

The BAP poster is available on the Targacept website at www.targacept.com.

[Erbse1]

Targacept Initiates Phase I Clinical Trial of TC-5619

Thursday July 26, 8:55 am ET

WINSTON-SALEM, N.C.--(BUSINESS WIRE)--Targacept, Inc. (NASDAQ: TRGT - News), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics(TM), today announced that it has initiated a Phase I clinical trial of TC-5619, a novel small molecule that modulates the activity of the neuronal nicotinic receptor (NNR) subtype known as alpha7. TC-5619 was discovered using Targacept's proprietary drug design technology known as Pentad(TM) and is the lead product candidate in its alpha7 NNR program.

"The entry of TC-5619 into the clinic further demonstrates the breadth and pharmacological diversity of our pipeline of NNR Therapeutics," said J. Donald deBethizy, Ph.D., Targacept's President and Chief Executive Officer. "The broad therapeutic application of the alpha7 NNR is well established and presents multiple opportunities for potential later stage development of TC-5619. We are also excited by the promise of other alpha7 compounds in our portfolio."

The Phase I study is designed to evaluate the safety, tolerability and pharmacokinetics of TC-5619. The trial is a double-blind, placebo-controlled study with single escalating doses of TC-5619 administered orally to healthy volunteers.

The alpha7 NNR is associated with a variety of biological functions. In particular, the alpha7 NNR has been shown in animal studies to be an essential regulator of both inflammation arising from injury or infection and cognitive functions. Published in vitro studies have also suggested that the alpha7 NNR plays a role in protecting neuronal cells from deterioration and death, a process known as neuroprotection.

[Erbse1]

Super deal, auf gehts.

GlaxoSmithKline and Targacept Form Alliance in Therapeutics for CNS-related Disorders

Friday July 27, 7:30 am ET


LONDON & PHILADELPHIA & WINSTON SALEM, N.C.--(BUSINESS WIRE)--GlaxoSmithKline (GSK) and Targacept, Inc. (NASDAQ: TRGT - News) today announced a strategic alliance to discover, develop and market novel therapeutics that selectively target specified neuronal nicotinic receptors (NNRs).

The alliance includes Targacept's lead product candidates for pain: TC-2696, which is currently in a Phase 2 trial for acute post-operative pain, and TC-6499, a preclinical product candidate that is currently planned for development for neuropathic pain. Targacept has retained an option to co-promote TC-2696 and TC-6499 for pain to specialists and hospital-based physicians in the United States.

Leveraging Targacept's more than 20 years of focused research in the NNR field, the alliance also provides GSK with access to other discovery programs across five therapeutic focus areas. In addition to pain, the other therapeutic focus areas of the alliance are smoking cessation, obesity, addiction, and Parkinson's disease.

Under the terms of the agreement, GSK will make an initial upfront payment of $35.0 million to Targacept, which includes an investment of $15.0 million for the purchase of 1,275,502 shares of Targacept common stock. In addition, Targacept is eligible to receive up to $1.5 billion in payments from GSK, contingent on the achievement of specified discovery, development, regulatory and commercial milestones across five therapeutic focus areas, as well as tiered double-digit royalties dependent on sales achieved.

In the alliance, Targacept will utilize its proprietary Pentad(TM) drug discovery technology to discover novel small molecule product candidates that target specified NNR subtypes and then would develop the most promising product candidate for each therapeutic focus area through a Phase 2 proof of concept trial. Targacept is eligible to receive success-based progress milestones from GSK as product candidates are advanced. Upon Targacept's achievement of clinical proof of concept for a lead product candidate for a particular therapeutic focus area, GSK would have an exclusive option to license product candidates in development in the alliance from that program. GSK would then assume full responsibility for funding of further clinical development and commercialization on a worldwide basis.

"The breadth of this alliance validates the importance of NNRs in the potential treatment of a broad range of CNS-related disorders and diseases," said J. Donald deBethizy, Ph.D., President and Chief Executive Officer of Targacept. "This uniquely structured deal enables us to accelerate the progression of our pipeline, capitalize on our discovery and development expertise and leverage the resources of a premier global pharmaceutical company while retaining considerable value. The alliance also aligns with our business strategy to progress our pipeline through human proof of concept and partner selectively for late-stage development and commercialization in primary care fields."

GSK will participate in the alliance through its Center of Excellence for External Drug Discovery (CEEDD). Hugh Cowley, M.D., Senior Vice President and head of the CEEDD said, "This alliance provides us access to innovative science and pioneering research and expertise in the promising NNR field. We believe there is tremendous potential for NNR therapeutics for a variety of CNS-related diseases and disorders, and look forward to working with Targacept to accelerate the development and delivery of new medicines to patients."

Targacept will be holding a conference call today at 10:00 a.m. Eastern Time to discuss the alliance in more detail. Call details will be provided in a separate release.

About Neuronal Nicotinic Receptors (NNRs)

NNRs represent a new class of therapeutic targets with the potential to address significant unmet medical needs. NNRs are members of the superfamily of neurotransmitter-gated ion channel receptors and play a central role in modulating synaptic neurotransmission, fundamental intracellular signaling pathways, neuronal viability and synaptic architecture and function. Recent advances in NNR biology derive from an increased understanding of individual receptor subtypes, their genetic heterogeneity, and their diverse biological functions. Both preclinical and clinical evidence demonstrate the broad potential of NNRs as targets for novel therapies to treat dementia and neurodegenerative diseases, psychotic disorders such as schizophrenia, inflammatory diseases, acute nociceptive and neuropathic pain, and affective disorders such as major depression.

Na dann schönen Tag noch
Erbse

[Erbse1]

Hier ein aktueller Artikel zu Targacept über die derzeitige Situation. Somit läßt sich fast sorgenfrei in die Zukunft schauen und in Ruhe zu arbeiten. Hoffen wir jetzt nur noch, daß die Wirkstoffe letztendlich auch erfolgreich abschließen können.

Schönen Tag noch
Erbse

Targacept NNR Platform Lands In Billion-Dollar GSK Alliance
By Jennifer Boggs

Targacept Inc. got an impressive stock boost Friday, jumping 20 percent on an early stage deal with GlaxoSmithKline plc to develop drugs targeting neuronal nicotinic receptors for pain and other disorders.

The alliance is accompanied by a $35 million up-front payment, comprised $20 million in cash and $15 million in an equity investment. London-based GSK agreed to purchase 1.3 million shares of Targacept's common stock priced at $11.76 per share, a nice premium to Thursday's closing price of $9. Beyond that, Targacept is eligible to receive up to $1.5 billion in potential milestones - with $1 billion of that to come from pre-commercial achievements - upon the successful development of product candidates across five therapeutic areas: pain, smoking cessation, obesity, addiction and Parkinson's disease. Targacept also would receive tiered double-digit royalties, depending on product sales.

"These are the kinds of deals that come along once in a lifetime," said Donald deBethizy, president and CEO of Targacept. "We've been celebrating."

The excitement was echoed on Wall Street, which sent shares of Targacept (NASDAQ:TRGT) up $1.79, or 20 percent, to close at $10.79.

Analyst Terence Flynn, of Lazard Capital Markets, maintained a "buy" rating on the company's stock and wrote in a research note that the GSK alliance further validates "the concept of targeting nicotinic receptors for therapeutic purposes and . . . the strength of Targacept's pipeline and Pentad discovery platform."

It's a platform that the Winston-Salem, N.C.-based firm has been perfecting since its days as a subsidiary of the R. J. Reynolds Tobacco Co. aimed at studying the chemistry and biology of nicotine. The company focuses on a class of drugs targeting neuronal nicotinic receptors (NNRs), which are found on nerve cells and work to regulate the central nervous system.

Targacept's Pentad technology is designed to discover small-molecule drugs targeting NNRs, and the company has identified a range of potential indications, such as Alzheimer's disease, schizophrenia, anxiety and pain, to name a few.

"We knew we had a great" platform, deBethizy told BioWorld Today, and "we've been chomping at the bit to get enough resources to get some of the discovery deals going."

Enter GSK, which signed Targacept under its Centers of Excellence for External Drug Discovery (CEEDD) program, which aims at building the pharma company's pipeline by investing in early biotech efforts.

Mark Strobeck, vice president of drug discovery transactions for GSK, said during a conference call that the goal of CEEDD is to allow a biotech firm "to partner with a large pharmaceutical company earlier in the development process and maintain its independence through clinical proof of concept," all the while receiving a stream of success-based funding.

Those kinds of early stage deals are becoming an industry trend. "There's a lot of new science emerging, so people are starting to take a little more risk," deBethizy said. As a result, biotech firms are able to sign preclinical deals "with Phase IIb economics."

As part of its role in the collaboration, Targacept will be responsible for research and discovery of small-molecule therapies that target predefined NNR subtypes and then will develop the most promising candidate in each of those five therapeutic areas through proof-of-concept studies. After that, GSK would have the option to take the programs into late-stage development and commercialization. And one of the best parts of the deal, deBethizy said, is that the financial structure ensures Targacept adequate funding for its work. Up to $16 million in milestones could be doled out for each of the five therapeutic programs prior to starting proof of concept.

Though alliance negotiations initially included only preclinical programs, Targacept's two lead pain products soon were added to the mix. TC-2696, which is designed to modulate the activity of the alpha4beta2 NNR, is in a Phase II trial for acute postoperative pain in patients undergoing third molar extraction, and pending successful results, expected by the end of this year, will enter a proof-of-concept trial. Following behind is TC-6499, which also targets the alpha4beta2 NNR. That compound is slated to start clinical testing before the end of 2007.

For both pain products, Targacept has retained a co-promotion option in the U.S. "We want to make sure we hold on to specialty opportunities," deBethizy said, adding that the company has a similar arrangement in its potential $300 million 2005 deal with London-based AstraZeneca plc. That collaboration includes TC-1734, now AZD3489, which started a 500-patient Phase IIb trial earlier this month in Alzheimer's disease. AstraZeneca is expected to start a separate Phase IIb study next month to test the compound in cognitive deficits in schizophrenia. (See BioWorld Today, Dec. 29, 2005.)

Targacept also is progressing clinical candidates on its own. Earlier this month, the company started a Phase I trial of TC-5619, a small molecule aimed at modulating the alpha7 NNR, believed to regulate inflammation arising from injury or infection, with possible implications on cognitive function. It also is in Phase I with TC-2216, which modulates alpha4beta2 to treat depression and anxiety.

Targacept, which has not yet reported its second-quarter earnings, posted a net loss of $4.8 million for the three months ending March 31. Alan Musso, the company's vice president and chief financial officer, reported during the conference call that the firm's current cash position, including the $35 million up-front payment from GSK, exceeds $90 million. He added that Targacept should end the year with about $75 million in the bank.

Quelle: http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher…

[Erbse1]

Aus aktuellem Anlass das Schaubild mit der Pipeline von Targacept. Toll, daß praktisch die gesamte vorklinische Pipeline für 1,5 Milliarden Dollar auslizensiert wurde.

[Erbse1]

Überblick aus dem Quartalsbericht.

Cash Ende des Jahres 2007 ca. 75 Millionen$
Recent Highlights
AstraZeneca initiated a Phase IIb clinical trial of AZD3480 (TC-1734) in mild to moderate Alzheimer's disease, with plans to initiate a separate Phase IIb clinical trial of AZD3480 (TC-1734) in cognitive deficits in schizophrenia in August 2007;

Formed a strategic alliance with GlaxoSmithKline to discover, develop and market novel therapeutics that selectively target specified NNR subtypes in five therapeutic focus areas: pain, smoking cessation, obesity, addiction and Parkinson's disease;

Continued to conduct the ongoing Phase II clinical trial of TC-2696 in third molar extraction patients and remain on track for completion of the trial in the second half of 2007;

Presented data from the completed Phase II clinical trial of mecamylamine hydrochloride as an add-on therapy to citalopram hydrobromide, a treatment combination known as TRIDMAC(TM), at the 2007 Summer Meeting of the British Association for Psychopharmacology;

Conducted additional preparatory activities for the potential clinical development of TC-5214, an enantiomer of mecamylamine hydrochloride;

Continued to conduct the ongoing Phase I clinical trial of TC-2216, a selective inhibitor of the alpha4beta2 NNR in development for depression and anxiety disorders;

Initiated a Phase I clinical trial of TC-5619, the most advanced compound in Targacept's chemically diverse alpha7 NNR program;

Continued to conduct manufacturing activities necessary to support the planned initiation of clinical development of TC-6499, a preclinical product candidate for neuropathic pain, in the second half of 2007;

Added Ralph Snyderman, M.D., an internationally recognized health care expert who combines a distinguished career in medicine with substantial industry experience, to the board of directors; and J. Donald deBethizy, President and Chief Executive Officer, testified before the Senate Committee on Health, Education, Labor and Pensions Subcommittee on Retirement Security and Aging on current and future breakthrough research in Alzheimer's disease.

Quelle: http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=118654524…

[Erbse1]

Kommentar des NeuroInvestor zur aktuellen Lage.

Targacept:
AstraZeneca has launched two PhIIb trials for TC-1734: a 500pt Alzheimer's study, and a 400pt schizophrenia trial, where TC-1734 is an adjunct to antipsychotic therapy. Data will not come from those trials until late next year. We expect that Targacept and AstraZeneca will expand the deal, to fold in TC-5619 for schizophreniform cognition. The depression possibilities for Targacept are more diffuse: they have mecamylamine, but they are choosing to instead develop its enantiomer TC-5214, which at the very least, offers patent protection. There is also TC-2216, an inhouse designed compound. A dental pain acute pain trial for TC-2696 is now expected to produce data near year-end. GSK. Pain, Parkinson's, obesity, addiction are all covered. The most important attribute, reflected in the $35 million upfront ($20 million via equity buy) and the $1.5 billion in theoretically available biobucks in milestones and royalties, is the distinct sense of collegiality in the deal. Targacept's ongoing contributions to the discovery/development process led GSK to pay Phase II prices for what is primarily a preclinical platform. As it should.

Quelle: http://www.neuroinvestment.com/Targacept.html

[Erbse1]

Folgend zwei Abstrakte zu Targacept

Differential effects of TC-5214 [S-(+)-mecamylamine] and TC-5213 [R-(-)-mecamylamine] at low and high sensitivity human alpha4beta2 nicotinic receptors and in animal models of depression and anxiety

Major depression is a severe psychiatric disorder characterized by a wide range of symptoms that cause significant impairment in the ability to work, study, sleep, eat, and enjoy once pleasurable activities. Increases in cholinergic tone are associated with depressive symptoms in humans, which has led to the proposal of a cholinergic hypothesis of depression whereby management of hypercholinergic tone could potentially ameliorate symptoms. Interestingly, antidepressant drugs such as selective serotonin or norepinephrine reuptake inhibitors and tricyclic antidepressants also non-competitively antagonize neuronal nicotinic receptors (NNRs) at clinically relevant doses.
Recent clinical trials have demonstrated the potential of the classical nicotinic antagonist mecamylamine as an add-on therapy in treatment-resistant major depressive disorders. In preclinical pharmacology studies we have found that TC-5213 (R-(-)-mecamylamine) non-competitively inhibits both HS (low calcium permeability high sensitivity) and LS (high calcium permeability low sensitivity) alpha4beta2 NNRs.

By comparison, TC-5214 (S-(+)-mecamylamine) inhibits LS with greater efficacy (Imax) but significantly facilitates agonist-induced activation of HS. In animal models of depression and anxiety (e.g., forced swim test, behavioral despair test, light-dark box, elevated plus maze), TC-5214 exhibited better in vivo efficacy than TC-5213. The present data demonstrate that TC-5214 exhibits higher potency, efficacy and selectivity than TC-5213 or mecamylamine racemate and that the hypercholinergic tone associated with depressive states may involve differential involvement of HS and LS alpha4beta2 NNRs.

[Erbse1]

TC-6499: an orally effective and selective alpha4beta2 neuronal nicotinic receptor agonist with anti-allodynic activity

The therapeutic potential of nicotinic ligands in pain management has been well established. Unfortunately, similar to most analgesics on the market, many compounds with activity at neuronal nicotinic receptors (NNRs) demonstrate adverse side effects, mediocre potency and/or limited efficacy. This range of beneficial and detrimental effects is presumably the result of non-selective action of nicotinic drugs at different (peripheral and central) cholinergic receptor subtypes.

The results reported herein summarize the in-vitro and in-vivo profile of a novel selective alpha4beta2 NNR agonist, TC-6499, which demonstrates a promising overall preclinical drug profile for neuropathic pain management in humans. TC-6499 has a high binding affinity for alpha4beta2 (Ki =27 nM), and exhibits substantially less activity at the alpha7 NNR or the alpha3beta2 or alpha3beta4 nAChRs compared to nicotine. Functionally, TC-6499 was shown to be an agonist at the alpha4beta2 receptor (120%) and in a DA release model (Emax = 114% of nicotine). Furthermore, electrophysiology studies indicate that TC-6499 has agonist activity at both high and low sensitivity alpha4beta2-containing NNR subtypes. It is readily absorbed following oral administration and has favorable pharmacokinetics.

TC-6499 is active in promoting anti-allodynia following acute and repeat administration with demonstrated effectiveness in animal models of neuropathic pain. Specifically, TC-6499 significantly reversed tactile allodynia in a model of diabetic neuropathy (STZ-induced) when administered both acutely (0.1 and 1 mg/kg; p.o.) and following repeat administration (0.1-10 mg/kg p.o.). TC-6499 was also efficacious in reversing tactile allodynia in a chemotherapy-induced neuropathy model (paclitaxel-induced; 0.01-1 mg/kg p.o.). TC-6499 exhibits a quicker onset of action (i.e., 30 min) and comparable efficacy and duration of action compared to gabapentin.

The compound demonstrated a favorable safety margin in preclinical safety studies, including in vitro and in vivo cardiovascular studies, acute and 14-day repeat dose studies, definitive 90-day studies and a full complement of genotoxicity studies. Overall, results of preliminary studies with TC-6499 provide evidence for a neuronal nicotinic modulator with potential efficacy in controlling neuropathic pain and a superior composite profile compared to previously characterized analgesic compounds acting via nicotinic or other neuronal mechanisms.

[Erbse1]

Targacept Announces Initiation of Phase IIb Development of AZD3480 (TC-1734) for Cognitive Deficits in Schizophrenia

Targacept, Inc. (NASDAQ: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics(TM), today announced that its strategic collaborator AstraZeneca has initiated a Phase IIb clinical trial of AZD3480 (TC-1734) in cognitive deficits in schizophrenia, or CDS.

Schizophrenia is a chronic, severe and disabling form of psychosis that, in addition to symptoms such as delusions and hallucinations, is often marked by impairments in cognitive functions such as attention, vigilance, memory and reasoning.

These cognitive impairments play a primary role in the inability of schizophrenic patients to function normally. It has been estimated that there are 8.4 million schizophrenic patients in the major markets worldwide, and that approximately 75% of all schizophrenic patients are cognitively impaired. There is currently no product approved for the treatment of CDS.

“Schizophrenia remains one of the top 10 disabling conditions worldwide for young adults,” said Dawn I. Velligan, Ph.D., Professor at the Department of Psychiatry at the University of Texas Health Science Center at San Antonio and co-director of the Health Science Center’s Division of Schizophrenia and Related Disorders. Velligan explained that although current antipsychotic medications may decrease the frequency of hallucinations and the degree of conviction in false beliefs, which are referred to as “positive” symptoms of schizophrenia, they often do not lead to successful long-term outcomes for schizophrenic patients.

“The development of medications that improve cognition in this illness is extraordinarily important in working toward improvement in the quality of life for individuals with schizophrenia,” Velligan said, noting that cognitive deficits frequently limit the ability of individuals with schizophrenia to learn in rehabilitation programs. “From a clinical perspective, we need to understand whether patients have adequate independent living skills to function in the community.” Velligan said that examples of such skills include taking the bus, keeping one’s living space clean, going to work, remembering to take medication, starting conversations with others, and maintaining friendships.

The CDS trial is a double blind, placebo controlled study being conducted at sites in the United States and Canada. The trial design provides for approximately 400 patients currently taking medication from the class known as atypical anti-psychotics to be randomly assigned to one of three dose groups of AZD3480 or to placebo and to be dosed over a 12-week period. The primary outcome measure of the trial is a cognitive test battery that includes assessments of cognitive functions across nine different domains and was developed in connection with a National Institute of Mental Health initiative known as Measurement and Treatment Research to Improve Cognition in Schizophrenia, or MATRICS. Secondary measures include measures of life functioning, such as performance in day-to-day tasks and social skills. The trial is expected to complete by the end of 2008.

“Research has shown that almost ninety percent of schizophrenics smoke,” said J. Donald deBethizy, Ph.D., President and Chief Executive Officer of Targacept. “One explanation for this high rate of smoking is that schizophrenic patients may be self-medicating with nicotine in order to address the cognitive impairment associated with the disease and thus function better. However, unlike nicotine, which acts non-selectively throughout the central and peripheral nervous system and therefore has an undesirable side effect profile, AZD3480 was designed to target select neuronal nicotinic receptors that studies have shown to play a role in cognition to promote therapeutic effects and limit adverse side effects.”

Bob Holland, Vice President and Head of the Neuroscience Therapy Area, AstraZeneca, added, “As suggested by our two ongoing Phase IIb trials, we are enthusiastic about the cognitive effects of AZD3480 and its potential for treating cognitive deficits in schizophrenia and Alzheimer’s disease, two areas where the unmet medical need is very high.”

AZD3480 has been evaluated to date in 12 clinical trials in approximately 540 subjects. In a previous Phase IIb clinical trial conducted by Targacept in age associated memory impairment, AZD3480 achieved statistically significant results on all of the primary endpoints, reflecting improved cognitive performance by memory-impaired older adults.

[Erbse1]

Nicotinic interactions with antipsychotic drugs, models of schizophrenia and impacts on cognitive function.
Levin ED, Rezvani AH.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.

People with schizophrenia often have substantial cognitive impairments, which may be related to nicotinic receptor deficits, (alpha7 and alpha4beta2), documented in the brains of people with schizophrenia. The large majority of people with schizophrenia smoke cigarettes. Thus, nicotinic interactions with antipsychotic drugs are widespread. Complementary co-therapies of novel nicotinic ligands are being developed to add to antipsychotic therapy to treat the cognitive impairment of schizophrenia. Thus, it is critical to understand the interaction between nicotinic treatments and antipsychotic drugs. Nicotinic interactions with antipsychotic drugs, are complex since both nicotine and antipsychotics have complex actions. Nicotine stimulates and desensitizes nicotinic receptors of various subtypes and potentiates the release of different neurotransmitters. Antipsychotics also act on a verity of receptor systems. For example, clozapine acts as an antagonist at a variety of neurotransmitter receptors such as those for dopamine, serotonin, norepinepherine and histamine. In a series of studies, we have found that in normally functioning rats, moderate doses of clozapine impair working memory and that clozapine blocks nicotine-induced memory and attentional improvement. Clozapine and nicotine can attenuate each other's beneficial effects in reversing the memory impairment caused by the psychototmimetic drug dizocilpine. A key to the clozapine-induced attenuation of nicotine-induced cognitive improvement appears to be its 5HT(2) antagonist properties. The selective 5HT(2) antagonist ketanserin has a similar action of blocking nicotine-induced memory and attentional improvements. It is important to consider the interactions between nicotinic and antipsychotic drugs to develop the most efficacious treatment for cognitive improvement in people with schizophrenia.

PMID: 17714691 [PubMed - as supplied by publisher]

[Erbse1]

Aktueller Überblick zu den einzelnen Wirkstoffen. Kopie aus dem Halbjahresbericht. 4 weitere Wirkstoffe sind vorklinisch und reserviert für GlaxoSmithKline.
>>In addition, we announced in July 2007 that we entered into a product development and commercialization agreement with GlaxoSmithKline that sets forth the terms of an alliance designed to discover, develop and market product candidates that selectively target specified NNR subtypes in five therapeutic focus areas: pain, smoking cessation, obesity, addiction and Parkinson’s disease.<<

Our most advanced product candidates, in addition to AZD3480 (TC-1734), are described below.

• TC-2216 . TC-2216 is a product candidate that we are developing as a monotherapy for depression and anxiety disorders. We are currently conducting a Phase I single rising dose clinical trial of TC-2216.

• Mecamylamine hydrochloride and TC-5214 . In 2006, we completed a Phase II clinical trial of mecamylamine hydrochloride as an augmentation treatment to citalopram hydrobromide, a commonly prescribed treatment for depression marketed as Celexa in the United States, for major depression. We refer to this treatment combination as TRIDMAC. Mecamylamine hydrochloride is the active ingredient in Inversine, our only product approved by the U.S. Food and Drug Administration, or FDA, for marketing. TC-5214 is one of the enantiomers of mecamylamine hydrochloride. We have not yet conducted a clinical trial of TC-5214, but expect that we will elect to advance TC-5214 into clinical development as an augmentation treatment for major depression in lieu of further development of mecamylamine hydrochloride. We expect to confirm our plans with regard to the further development of TC-5214 or TRIDMAC following a meeting with the FDA that is scheduled to occur in August 2007.

• TC-2696. TC-2696 is a product candidate that we are developing currently as a treatment for acute post-operative pain. We are currently conducting a Phase II clinical trial of TC-2696 in third molar extraction patients. We expect the results of this trial to be available in the second half of 2007.

• TC-5619. TC-5619 is a preclinical product candidate that modulates the a 7 NNR for which we are currently conducting a Phase I single rising dose clinical trial. We believe compounds that selectively target the a 7 NNR may have application in the treatment of conditions such as schizophrenia, cognitive impairment and inflammation.


Under our agreement with AstraZeneca, we are entitled to offer to AstraZeneca the right to develop and commercialize TC-5619 as a treatment for any or all of schizophrenia and various conditions characterized by cognitive impairment under the terms of the agreement. We are currently engaged in discussions with AstraZeneca and are considering whether to offer this right to AstraZeneca. If we elect not to offer this right to AstraZeneca, we would generally be permitted to pursue the development and commercialization of TC-5619 outside of the collaboration only for indications other than schizophrenia and various conditions characterized by cognitive impairment. If we offer this right to AstraZeneca, AstraZeneca could license TC-5619 under the terms of the agreement. Alternatively, AstraZeneca could negotiate a development plan with us pursuant to which we would conduct development of TC-5619 through a Phase II clinical proof of concept trial, at which stage AstraZeneca could license TC-5619 under the terms of the agreement. If AstraZeneca were ultimately to elect not to license TC-5619, we would be permitted to develop and commercialize TC-5619 for any indication.

• TC-6499. TC-6499 is a preclinical product candidate that we plan to develop initially for neuropathic pain. We are currently conducting manufacturing activities necessary to support the planned initiation of clinical development of this product candidate in the second half of 2007.

[Erbse1]

Kleiner Artikel vom Deutschlandfunk zu Nikotin bei der Datenverarbeitung im Gehirn

Die Leitung denkt mit
Nervenleitungen helfen bei der Datenverarbeitung

Von Michael Lange
Medizin. - Gerne behaupten die Hirnforscher, dass sie dem Gehirn beim Denken zuschauen, wenn sie bunte Bilder aus der Magnetresonanz-Tomografie betrachten. Doch noch ist weitgehend unklar, wie das Denken funktioniert. Neue Forschungsergebnisse aus Kalifornien zeigen nun, dass auch die Nervenleitungen dabei eine wichtige Rolle spielen.

Die Hauptaufgabe von Nervenzellen im Gehirn ist es, Botschaften mit anderen Nervenzellen auszutauschen. Dazu müssen sie untereinander in Kontakt treten - über lange Zellausläufer, die Axone, fließen dann Informationen von Zelle zu Zelle. Verschiedene Substanzen wie das suchterzeugende Nikotin beeinflussen diesen Informationsfluss im Gehirn. Nikotin erhöht so vorübergehend die Aufmerksamkeit. Der Neurobiologe Raju Metherate von der Universität von Kalifornien wollte herausfinden, wie Nikotin auf Nervenzellen wirkt. Gemeinsam mit einigen Kollegen ließ er deshalb eine Art "Mäusegehirn in der Glasschale" wachsen, um daran Messungen an einzelnen Nervenzellen durchzuführen.

Wir haben das Gehirngewebe so präpariert, dass wir die Wirkung des Nikotins auf den Fluss der Botenstoffe genau verfolgen konnten. Aber wir waren nicht in der Lage, die erwarteten Effekte in den Zellen selbst zu messen. Erst als wir uns die Axone genauer anschauten, wurden wir fündig. Axone sind die langen, dünnen Verbindungskabel zwischen den Nervenzellen und zwischen verschiedenen Teilen des Gehirns.

Manche Nervenzellen besitzen nur ein paar Axone, andere hunderte. Unter dem Mikroskop sehen die Zellen zum Teil aus wie Tintenfische. Die vielen Arme sind die Axone. Sie bestehen hauptsächlich aus dünnen Eiweißfäden und transportieren das im Zellkörper erzeugte Signal zu den anderen Nervenzellen, die viele Zentimeter entfernt liegen können. Elektrische Ladungen wandern dabei durch die isolierten Nervenleitungen. Es fließt ein schwacher elektrischer Strom. Ein heißer Draht von Zelle zu Zelle, mehr nicht. Das dachte man bisher. Die jetzt veröffentlichten Ergebnisse von Raju Metherate liefern ein neues Bild.

Wenn wir diesen einfachen Draht anregen, zum Beispiel mit Nikotin, dann reagiert er. Er verstärkt das Signal, oder schwächt es ab. Wir haben damit erstmals gezeigt, dass in den Axonen Informationen verarbeitet werden. Wie das genau abläuft, wissen wir noch nicht. Aber wir wissen: Die Axone sind der Ort der Handlung.

Raju Metherate vermutet: Jeder Gedanke, jede Wahrnehmung wird von den Axonen nicht nur weitergeleitet, sie wird verarbeitet und verändert. Das hieße: das Denken findet nicht nur in den "grauen Zellen" statt, sondern auch in den Verbindungskabeln dazwischen. Im Gehirn sehen Bereiche mit vielen Axonen weiß aus. Die weiße Substanz im Gehirn besteht aus vielen gebündelten Axonen. Schizophrenie-Patienten haben vergleichweise wenig von dieser weißen Substanz, also zu wenig Axone. Es fehlen Nervenleitungen. Das brachte Raju Metherate auf eine Idee.

Es ist bekannt, dass fast neunzig Prozent aller Schizophrenie-Patienten rauchen. Jetzt wissen wir warum. Indem sie ihre Axone mit Nikotin aktivieren, versuchen sie, ihre Symptome zu bekämpfen.

Der gleiche Effekt müsste sich auch ohne die schädlichen Wirkungen des Rauchens erzielen lassen. Ein Medikament könnte die Axone aktivieren, ohne Sucht zu erzeugen oder die Lunge zu schädigen. Die Umsetzung dieser Idee ist allerdings nicht mehr eine Aufgabe für Grundlagenforscher, sondern für Pharmazeuten.
Quelle: http://www.dradio.de/dlf/sendungen/forschak/663360/

[Erbse1]

Targacept Milestones 2007

[Erbse1]

Update Pipeline Targacept 23 September 2007

[Erbse1]

Antwort auf Beitrag Nr.: 31.711.236 von Erbse1 am 23.09.07 17:26:38

Update Pipeline Targacept 20.10.2007

[Erbse1]

Targacept Announces Plans to Develop Enantiomer of Mecamylamine as Augmentation Therapy for Depression
Poster Presented at 20th ECNP Congress Illustrates Favorable Preclinical Profile for TC-5214

Winston-Salem, NC

October 23, 2007

Targacept, Inc. (NASDAQ: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics (TM), today announced plans to advance TC-5214, one of two enantiomers of mecamylamine hydrochloride, into clinical development as an augmentation therapy for patients who are inadequate responders to first-line antidepressant treatments. Targacept expects to initiate a Phase 1 trial of TC-5214 in the first quarter of 2008 and to initiate Phase 2 development soon thereafter. The company has no current plans to conduct further clinical development of mecamylamine.

Mecamylamine hydrochloride is a racemic compound comprised of two mirror image halves known as the S+ and R- enantiomers. TC-5214 is the S+ enantiomer of mecamylamine. In a Phase 2 trial in patients who did not respond adequately to first-line treatment with citalopram hydrobromide that Targacept completed in 2006, patients whose citalopram regimen was augmented with mecamylamine showed greater improvement on symptoms of depression and irritability than patients who received citalopram and a placebo. Citalopram hydrobromide is a commonly prescribed treatment for depression from the drug class selective serotonin reuptake inhibitors that is marketed as Celexa (R) in the United States.

Targacept recently presented research findings comparing the activity of TC-5214, mecamylamine and the R- enantiomer of mecamylamine at the 20th European College of Neuropsychopharmacology held in Vienna, Austria. The results presented illustrate the superior potency of TC-5214 relative to mecamylamine at specific NNR subtypes believed to have therapeutic application for depression, as well as a favorable preclinical efficacy profile. In light of the Phase 2 results with mecamylamine described above, these findings suggest the compelling potential of TC-5214 as an augmentation treatment for major depression.

“Major depression is a serious medical illness affecting 15 million American adults, and the current treatment options simply are not adequate for many people,” said Ranga Krishnan, M.D., Chair of the Department of Psychiatry at the Duke University Medical Center and an internationally recognized expert in depression treatments. “The results from Targacept’s Phase II efficacy trial of mecamylamine as an augmentation therapy to citalopram helped establish the NNR mechanism as a potential new treatment paradigm for depression,” said Dr. Krishnan. “The profile of TC-5214 as a more potent NNR modulator than racemic mecamylamine bodes well for its potential to help address the unmet need.”

Targacept’s poster of preclinical research findings of TC-5214 is available on the company’s home page at www.targacept.com

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Parkinson: Kann Nikotin Dyskinesien nach L-Dopa mildern?

Sunnyvale – Könnte eine Nikotintherapie die Entstehung von Dyskinesien im Rahmen der L-Dopa-Behandlung des Morbus Parkinson abschwächen? Eine tierexperimentelle Studie in den Annals of Neurology (2007; doi: 10.1002/ana.21203) deutet darauf hin. Klinische Erfahrungen liegen jedoch noch nicht vor.

Das Striatum ist nicht nur das Ziel jener dopaminerger Neurone, deren Degeneration in der Substantia nigra die Ursache des Morbus Parkinson ist. Es gibt in diesem Teil der Basalganglien auch zahlreiche Neurone mit nikotinergen Acetylcholinrezeptoren. Wie beide miteinander vernetzt sind, ist unbekannt. Parkinsonforscher wie Maryka Quik und Mitarbeiter vom Parkinson Institute in Sunnyvale/Kalifornien sind jedoch überzeugt, dass eine Stimulation dieser Rezeptoren günstige Auswirkungen auf den Verlauf des Morbus Parkinson hat. Als Beleg führen sie epidemiologische Untersuchungen an, die in den letzten 40 Jahren immer wieder gezeigt hätten, dass Raucher zu 50 Prozent seltener an einem Morbus Parkinson erkranken.

Um den therapeutischen Effekt einer Nikotingabe zu untersuchen, induzierten die Forscher bei Versuchstieren (Totenkopfaffen, Saimiri sciureus) durch die Gabe des Nervengifts MPTP einen Parkinsonismus, der dann mit L-Dopa behandelt wurde. Einem Teil der Tiere (im Coss-over-Design) wurde zusätzlich Nikotin ins Trinkwasser gegeben mit dem Ergebnis, dass die Rate der Dyskinesien, eine der am meisten gefürchteten Nebenwirkungen der langfristigen L-Dopa-Therapie, um 35 Prozent abnahm. Dabei hatte die Nikotingabe keine Auswirkungen auf die Wirksamkeit von L-Dopa.

Ob die Therapie auch bei Menschen mit L-Dopa sinnvoll ist, bleibt abzuwarten. Zu bedenken ist, dass die tierexperimentellen Studien nur über einen Zeitraum von 8 Wochen durchgeführt wurden. Eine Begleitbehandlung mit Nikotinpflastern (oder anderen aus der Substitutionstherapie zur Raucherentwöhnung bekannten Formulierungen) müsste jedoch längerfristig erfolgen. Dabei kommt es dann rasch zu einer Desensitivierung der Nikotinrezeptoren, wie die Autoren selbst zu bedenken geben.

Art und Zeitpunkt der Applikation könnten deshalb darüber entscheiden, ob die Therapie langfristig erfolgreich ist. Klinische Studien wären deshalb sinnvoll, zumal es in der Medizin nicht selten ist, dass die Ergebnisse aus tierexperimentellen Studien nicht auf den Menschen übertragbar sind.

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Targacept to Receive $2 Million from AstraZeneca for Option to Lead Product Candidate in Alpha7 NNR Program
Winston-Salem, North Carolina

November 05, 2007

Targacept, Inc. (NASDAQ: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics (TM), today announced that AstraZeneca has secured an option for an exclusive license to Targacept’s product candidate TC-5619 under the terms of the parties’ collaboration agreement. As a result, AstraZeneca will make a $2.0 million payment to Targacept.

Neuronal nicotinic receptors (NNRs) are a class of receptors found in the nervous system that play a critical role in modulating the release of chemicals called neurotransmitters to regulate nervous system activity. The alpha7 NNR subtype has been shown in animal studies to be a key regulator of cognitive function. TC-5619, the lead product candidate in Targacept’s alpha7 NNR program, entered Phase I clinical development in July 2007. The parties’ expansion of their collaboration to include TC-5619 reflects the potential of the alpha7 NNR as a therapeutic target for cognitive disorders.

“Our decision to secure an option to license TC-5619 under our collaboration agreement underscores AstraZeneca’s enthusiasm for the promise of NNRs as a new mechanism for the treatment of cognitive disorders,” said Bob Holland, Vice President and Head of the Neuroscience Therapy Area, AstraZeneca. “We are committed to developing novel therapies in areas of unmet need such as Alzheimer’s disease, cognitive deficits in schizophrenia and other cognitive disorders and are delighted to be able to access Targacept’s innovation in this field.”

Targacept and AstraZeneca entered into their exclusive global license and research collaboration agreement in December 2005, initially for the development and commercialization of another of Targacept’s NNR Therapeutics, TC-1734, which AstraZeneca refers to as AZD3480. AstraZeneca is currently conducting Phase IIb clinical trials of AZD3480 (TC-1734) in each of Alzheimer’s disease and cognitive deficits in schizophrenia.

“The progress to date in our AstraZeneca collaboration has been impressive,” said J. Donald deBethizy, Ph.D., Targacept’s President and Chief Executive Officer. “AstraZeneca’s ongoing Phase IIb proof of efficacy trials of AZD3480 in Alzheimer’s disease and cognitive deficits in schizophrenia are together expected to enroll approximately 900 patients, with both trials on track to complete in the second half of 2008. Beyond that, our funded preclinical research collaboration is yielding additional novel product candidates targeting the alpha4beta2 NNR subtype, and we are now introducing TC-5619, an alpha7 NNR agonist, into the collaboration. We are very fortunate to be working closely with AstraZeneca as we progress our portfolio of NNR Therapeutics for the treatment of cognitive disorders.”

Notes to editors:
AstraZeneca’s election to secure an option to license TC-5619 was triggered under the collaboration agreement by Targacept’s decision to pursue its development for cognitive disorders. AstraZeneca’s election allows Targacept to continue developing TC-5619 independently through a Phase II clinical proof of concept trial. At that point, if TC-5619 achieves clinical proof of concept, AstraZeneca has the option to pay Targacept $40 million for an exclusive license for TC-5619 for various conditions characterized by cognitive impairment. If AstraZeneca exercises its option, it would assume responsibility for and fund all later-stage development and commercialization of TC-5619 and Targacept would be eligible to receive additional payments of up to $226 million, contingent upon the achievement of development, regulatory and first commercial sale milestones, and stepped double-digit royalties on any future product sales. If TC-5619 does not achieve clinical proof of concept but AstraZeneca remains interested in a potential license, the collaboration agreement provides a mechanism for the parties to negotiate terms.

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Targacept Announces Results of Phase II Study of TC-2696 in Postoperative Dental Pain


TRGT 9.60, +0.12, +1.3%) , a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics (TM), today announced results of a randomized, placebo controlled Phase II clinical trial of its product candidate TC-2696. In the trial, 181 patients received a single dose of one of three doses of TC-2696 or ibuprofen or placebo following third molar extraction surgery. TC-2696 did not meet the primary endpoints, superior pain relief four or six hours after dosing as compared to placebo. TC-2696 was generally well tolerated in the trial, as there were no clinically meaningful differences in the incidence of adverse events between the TC-2696 dose groups and the placebo group and no unexpected or serious adverse events. These results suggest that TC-2696 is not a viable therapeutic candidate for acute post-operative pain.
In Targacept's preclinical studies, TC-2696 demonstrated analgesic activity in a variety of models, including acute, chronic and inflammatory nociceptive pain and neuropathic pain. Targacept is continuing to analyze the data from the trial and plans to consider next steps with regard to the development of TC-2696 in conjunction with GlaxoSmithKline, with which it entered into a strategic alliance focused in five therapeutic areas, including pain, earlier this year.

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Schizophrenia And Smoking: Weighing The Role Of The Tobacco Industry
8 December 2007. The prevalence of cigarette smoking in the United States has declined precipitously over the past four decades to about 20 percent of the general adult population, half what it was when the Surgeon General released the landmark 1964 report on smoking and health (Centers for Disease Control and Prevention [CDC], 2007). However, cigarette smoking is twice as common among the mentally ill as in the general population (Lasser et al., 2000), which translates into $37 billion in annual sales for the tobacco industry. The prevalence of smoking among those diagnosed with schizophrenia is particularly striking, with some researchers proposing rates as high as 88 percent (Hughes et al., 1986).

A new report, published online November 5, 2007, in Schizophrenia Bulletin, by Judith Prochaska and colleagues at the University of California, San Francisco proposes that a concerted, multi-pronged effort by that industry has sustained the high rate of smoking among patients with schizophrenia, both by promoting their use of cigarettes and by discouraging smoking bans and smoking cessation programs in psychiatric hospitals.

Smoking is not hazardous to your health?
For their study, the UCSF team relied on word-searchable databases, such as the Legacy Tobacco Documents Library, of the nearly 40 million pages of internal tobacco industry documents that were made publicly available after a 1998 judgment against the industry by the State of Minnesota. Based on the information in documents retrieved by broad keyword searches (e.g., “psychosis”), the Prochaska group performed progressively restricted searches based on names of programs and individuals, dates, and reference numbers. The preliminary search yielded 280 documents, 130 of which were from the archive of the Council for Tobacco Research (CTR), an industry organization originally founded in the mid-1950s to fund research that could be used in public relations campaigns to counter the growing tide against cigarette smoking.

According to the UCSF team, the documents reveal that promotional tactics of the tobacco industry toward individuals with schizophrenia took two main forms. First, they funded research to corroborate the idea, largely based on anecdotal evidence, that individuals with schizophrenia have some psychosomatic or genetic profile that bestows resistance to tobacco-related diseases. They also backed studies of the hypothesis that the high rate of smoking among patients with schizophrenia represented a beneficial form of “self-medication,” presumably mediated by nicotinic acetylcholine receptors. Second, either directly or in collaboration with patient advocacy groups, the industry took steps to see that psychiatric patients had easy access to cigarettes and that smoking bans in psychiatric hospitals would either be lifted or substantially relaxed.

The authors found that as far back as the 1950s the industry was collecting correspondence and other material from medical journals proposing that patients with schizophrenia have low rates of cancer despite high rates of smoking. The CTR and other industry organizations funded studies—later discredited—asserting that patients with schizophrenia are less likely to develop cancer from smoking because they did not repress grief and other emotions as strongly as those in the general population.

Prochaska and colleagues cite a 1982 research grant proposal to the Canadian Tobacco Manufacturer’s Council (CTMC), wherein one investigator who planned to explore the self-medication hypothesis pointed out to the reviewers that positive findings would be a “significant bonus for the tobacco industry,” and indicated that patients who participated in the study would be paid in either cash or cigarettes. The Prochaska group found evidence that for both the disease-resistance and self-medication lines of inquiry, the industry denied funding to investigators whose grant requests entertained the possibility of negative findings, favoring researchers who approached these problems “from our point of view,” as Prochaska and colleages quote an internal company memo on a scientist who depended on CTMC money.

The documents reveal that only a fraction of industry-funded studies discussed in researchers’ progress reports were eventually published in peer-reviewed journals, a disparity that the Prochaska team takes as evidence that a great deal of unfavorable data may have been suppressed, a pattern they say has been paralleled in the industry’s research programs on harmfulness of secondhand smoke.

Forty years behind
Recent studies have revealed that individuals with schizophrenia have of higher risk of developing diseases associated with cigarette smoking, including lung cancer (Lichtermann et al., 2001), cardiovascular disease (Goff et al., 2005), and respiratory problems (Himelhoch et al., 2004), though the possible confounding effects of poor diet, lack of exercise, and side-effects of antipsychotic medications have not been fully sorted out (see related SRF news story).

Prochaska and colleagues suggest that the tobacco industry’s greatest damage to the health of patients with schizophrenia may be indirect: because the research enterprise has been skewed toward tobacco’s supposed harmlessness or beneficial effects, “astoundingly little” research has been published on smoking cessation among psychiatric patients. “Might it be,” the authors ask, “that the mentally ill are the largest remaining group of smokers, not because they need to smoke but rather because they are among the last to be treated?”—Peter Farley

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Targacept to Receive $6 Million from GlaxoSmithKline for Initiation of Phase I Trial of Neuropathic Pain Candidate

December 10, 2007

Targacept, Inc. (Nasdaq: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics (TM), today announced that it has initiated a Phase I clinical trial of its product candidate TC-6499. The initiation of the trial triggers a $6.0 million milestone payment to Targacept under the terms of its alliance agreement with GlaxoSmithKline.

TC-6499 is a novel small molecule that Targacept plans to develop initially as a treatment for neuropathic pain. In preclinical studies, TC-6499 demonstrated analgesic activity in multiple models of neuropathic pain. TC-6499 was discovered using Targacept’s proprietary drug design technology known as Pentad (TM).

The Phase I study is designed to evaluate the safety, tolerability and pharmacokinetics of TC-6499. The trial is a double-blind, placebo-controlled study with escalating single doses of TC-6499 administered orally to healthy volunteers.

“TC-6499 represents the third Pentad-enabled product candidate that we have advanced into the clinic this year, demonstrating the strength of Pentad, our ability to execute our operating plans successfully and the breadth and pharmacological diversity of our pipeline of NNR Therapeutics,” said J. Donald deBethizy, Ph.D., Targacept’s President and Chief Executive Officer. “We are pleased to achieve this milestone in our GlaxoSmithKline alliance, which we entered into only a few months ago.”

“We are delighted to see TC-6499 enter clinical development,” said Hugh Cowley, M.D., Senior Vice President of GlaxoSmithKline and head of the Center of Excellence for External Drug Discovery (CEEDD). “There is a clear need for effective treatments for neuropathic pain and the preclinical profile of TC-6499 is very encouraging. We are pleased to be working with Targacept and excited by the potential of NNR-targeted therapeutics for pain, as well as the other four therapeutic focus areas of the alliance.”

Targacept anticipates that its Phase I program for TC-6499 will include, in addition to the ongoing single dose trial, a multiple rising dose trial. Under its agreement with GlaxoSmithKline, Targacept is eligible to receive an additional milestone payment if, following completion of its Phase I program, Targacept determines to advance TC-6499 into Phase II.

TC-6499 is subject to a contingent future option of GlaxoSmithKline for an exclusive license under the terms of the parties’ agreement. If licensed, Targacept retains an option to co-promote TC-6499 for pain to specialists and hospital-based physicians in the United States.

About Neuropathic Pain

Unlike nociceptive pain, which generally results from tissue damage, neuropathic pain results from damage to the nerves that transmit pain sensation. When this occurs, central nervous system (CNS) mechanisms that inhibit pain transmission do not function properly and pain signals continue to be sent to the brain. NNR-targeted treatments may have the potential to amplify the inhibitory CNS mechanisms directly, restoring their ability to shut off the pain signals. Neuropathic pain is characterized as severe, stabbing, burning or tingling and is most often associated with diabetes mellitus, chemotherapy, toxins, herpes, HIV infection or trauma. Neuropathic pain affects more than 15 million people in the United States alone, and the currently available treatments are often inadequate to relieve the pain effectively. Other options are needed to improve the outcomes for patients with neuropathic pain.

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Das war abzusehen

GlaxoSmithKline has notified Targacept that it will not be making any payments to the company to secure an option on rights to a drug candidate known as TC-2696.

The Winston-Salem-based biotech company announced earlier this month that TC-2696 had failed to demonstrate effectiveness at relieving acute pain in a clinical trial. The drug was part of a development partnership between Targacept (NASDAQ: TRGT) and GSK.

Because GSK has declined to pay for the rights, Targacept said it is free to develop the drug independently or with other partners, but also said it has no current plans to do so.

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Update Targacept Ende 2007

TC-2696 lieferte keine signifikanten Ergebnisse und wurde gestoppt.
TRIDMAC wurde gestoppt,
TC-5214 wird im nächsten Qaurtal in der Anwendung Depression gestartet.
TC-6499 wurde in der Anwendung neuropatischer Schmerz gestartet.
TC-2216 Ergebnisse Phase 1 werden jetzt in den nächsten Tagen erwartet.
TC-1734 Ergebnisse werden Anfang 2009 erwartet.

Aktuelles Schaubild von der Targacept Pipeline

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Kapitalmaßnahme bei Targacept.
Wen wunderts, denn die Deutsche Bank sich letztes Quartal von ihrer dicken Position zu über 9 $ getrennt hat. Na ja, der Teufel scheißt immer auf den großen Haufen. Dann bis zur nächsten Kapitalmaßnahme im nächsten Jahr.

Targacept Announces the Pricing of a Public Offering of 3.8 Million Shares of its Common Stock

Thursday January 17, 8:55 am ET


WINSTON-SALEM, N.C.--(BUSINESS WIRE)--Targacept, Inc. (Nasdaq: TRGT) today announced the pricing of an underwritten public offering of 3.8 million shares of its common stock at a price to the public of $7.07 per share, which was the closing bid price of Targacept’s shares on the Nasdaq Global Market on January 16, 2008. Targacept has granted to the underwriters for the offering a 30-day option to purchase up to 570,000 additional shares of common stock to cover over-allotments, if any. All of the shares are being offered by Targacept. The closing of the offering is expected to take place on January 23, 2008, subject to satisfaction of customary closing conditions. Deutsche Bank Securities Inc. is the sole book-running manager for the offering. Lazard Capital Markets LLC, Oppenheimer & Co. Inc. and Pacific Growth Equities, LLC are co-managers for the offering.

The offering is being made pursuant to an effective shelf registration statement that Targacept previously filed with the Securities and Exchange Commission. This press release does not and shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction. Any offer will only be made by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. Copies of the final prospectus, including the prospectus supplement when filed, can be obtained from Deutsche Bank Securities Prospectus Department, 100 Plaza One, Second Floor, Jersey City, NJ 07311, telephone: [phone]

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Targacept Announces Exercise of Underwriters’ Overallotment Option and Closing of $30.9 Million Public Offering
Winston-Salem, North Carolina

January 24, 2008

Targacept, Inc. (Nasdaq: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics (TM), today announced that it has completed the previously announced underwritten public offering of shares of its common stock. The completed offering included 570,000 shares purchased by the underwriters upon exercise of their overallotment option. Targacept issued and sold a total of 4,370,000 shares in the offering, resulting in gross proceeds, before deducting underwriting discounts, commissions and offering expenses, of $30.9 million.

Deutsche Bank Securities Inc. was the sole book-running manager for the offering. Lazard Capital Markets LLC, Oppenheimer & Co. Inc. and Pacific Growth Equities, LLC were co-managers for the offering.

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Nicotine improves cognitive deficits of dopamine transporter knockout mice without long-term tolerance.
Weiss S, Nosten-Bertrand M, McIntosh JM, Giros B, Martres MP.
Inserm, U513, Laboratoire de Neurobiologie et Psychiatrie, University Paris 12, Créteil, France.

Various studies suggest a dysfunction of nicotinic neurotransmission in schizophrenia and establish that patients suffering from schizophrenia and attention deficit hyperactivity disorder (ADHD) have a high tobacco consumption, potentially for the purpose of self-medication. Owing to its neuroprotective and procognitive effects, transdermal nicotine was proposed to be an effective treatment of some neurodegenerative and psychiatric diseases. Mice deficient in the dopamine transporter (DAT KO) exhibit a phenotype reminiscent of schizophrenia and ADHD, including hyperdopaminergia, hyperactivity, paradoxical calming by methylphenidate and cognitive deficits, some of which being improved by antipsychotic agents. We recently demonstrated that nicotinic receptor content and function were profoundly modified in DAT KO mice. In this study, we assessed the effects of a chronic nicotine treatment in the drinking water on the nicotine-induced locomotion, anxiety status and learning performance. Chronically nicotine-treated DAT KO mice were always hypersensitive to the hypolocomotor effect of nicotine without tolerance and did not exhibit the anxiogenic effect of nicotine treatment observed in WT mice. Very interestingly, both acute and chronic nicotine treatments greatly improved their deficits in the cued and spatial learning, without eliciting tolerance. We speculate that the procognitive effects of nicotine in DAT KO mice are related to the upregulation of alpha7 nicotinic receptors in the hippocampus, amygdala, and prelimbic cortex, all areas involved in cognition. Data from our studies on DAT KO mice shed light on the nicotine self-medication in psychiatric patients and suggest that nicotinic agonists could favorably lead to additional therapy of psychiatric diseases.

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Nicotine improves cognitive deficits of dopamine transporter knockout mice without long-term tolerance.
Weiss S, Nosten-Bertrand M, McIntosh JM, Giros B, Martres MP.
Inserm, U513, Laboratoire de Neurobiologie et Psychiatrie, University Paris 12, Créteil, France.

Various studies suggest a dysfunction of nicotinic neurotransmission in schizophrenia and establish that patients suffering from schizophrenia and attention deficit hyperactivity disorder (ADHD) have a high tobacco consumption, potentially for the purpose of self-medication. Owing to its neuroprotective and procognitive effects, transdermal nicotine was proposed to be an effective treatment of some neurodegenerative and psychiatric diseases. Mice deficient in the dopamine transporter (DAT KO) exhibit a phenotype reminiscent of schizophrenia and ADHD, including hyperdopaminergia, hyperactivity, paradoxical calming by methylphenidate and cognitive deficits, some of which being improved by antipsychotic agents. We recently demonstrated that nicotinic receptor content and function were profoundly modified in DAT KO mice. In this study, we assessed the effects of a chronic nicotine treatment in the drinking water on the nicotine-induced locomotion, anxiety status and learning performance. Chronically nicotine-treated DAT KO mice were always hypersensitive to the hypolocomotor effect of nicotine without tolerance and did not exhibit the anxiogenic effect of nicotine treatment observed in WT mice. Very interestingly, both acute and chronic nicotine treatments greatly improved their deficits in the cued and spatial learning, without eliciting tolerance. We speculate that the procognitive effects of nicotine in DAT KO mice are related to the upregulation of alpha7 nicotinic receptors in the hippocampus, amygdala, and prelimbic cortex, all areas involved in cognition. Data from our studies on DAT KO mice shed light on the nicotine self-medication in psychiatric patients and suggest that nicotinic agonists could favorably lead to additional therapy of psychiatric diseases.

PMID: 17375139 [PubMed - indexed for MEDLINE]

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Targacept strikes loan agreement with BB&TThe Business Journal of the Greater Triad Area^

Targacept has established a new loan facility with BB&T to help it acquire new, more efficient drug-discovery lab equipment.

The Winston-Salem-based Targacept (NASDAQ: TRGT) will be able to borrow up to $5.3 million under the loan agreement from BB&T (NYSE: BBT), which is also headquartered in the Twin City.

Targacept is already "well capitalized," said Chief Financial Officer Alan Musso, with $87 million of cash in the bank according to its most recent quarterly earnings report. But Musso said the company is upgrading its lab equipment to speed the drug discovery process in conjunction with its two major pharmaceutical partners, AstraZeneca and GlaxoSmithKline.

To conserve cash Targacept had been drawing on a line of credit last year, "but the interest rate environment has become much more favorable since then, so we're seeing some real interest savings" under the new loan terms, Musso said.

Musso said the expansion Targacept underwent in its Piedmont Triad Research Park headquarters last year has sufficient space for the new equipment, so no further expansions are planned for now.

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10K Update Targacept

Our lead product candidate is a novel small molecule that we have historically referred to as TC-1734 and that our strategic collaborator, AstraZeneca, refers to as AZD3480. AZD3480 (TC-1734) modulates the activity of the †4ß2 NNR. In December 2005, we entered into a collaborative research and license agreement with AstraZeneca AB for the development and worldwide commercialization of AZD3480 (TC-1734) as a treatment for Alzheimer's disease, cognitive dysfunction in schizophrenia and potentially other conditions characterized by cognitive impairment such as ADHD, AAMI and MCI. AstraZeneca is currently conducting two Phase 2b clinical trials of AZD3480 (TC-1734), one in mild to moderate Alzheimer's disease, which is referred to as the "Sirocco" trial, and one in cognitive dysfunction in schizophrenia, which is referred to as the "HALO" trial. Based on information provided to us by AstraZeneca, we expect that both trials will be completed by the end of 2008.

We and AstraZeneca are also conducting a preclinical research collaboration under the agreement that is designed to discover and develop additional compounds that, like AZD3480 (TC-1734), act on the †4ß2 NNR as treatments for conditions characterized by cognitive impairment. AstraZeneca pays us research fees, based on a reimbursement rate specified under the agreement, for research services rendered in the preclinical research collaboration, subject to specified limits. The research term began in January 2006 and has a planned term of four years.

In July 2007, we entered into a product development and commercialization agreement with GlaxoSmithKline. The agreement sets forth the terms of an alliance designed to discover, develop and market product candidates that selectively target specified NNR subtypes in five therapeutic focus areas: pain, smoking cessation, addiction, obesity and Parkinson's disease.

Our other clinical-stage product candidates, in addition to AZD3480 (TC-1734), are described below.

• TC-5619. TC-5619 is a novel small molecule that we plan to develop for cognitive dysfunction in schizophrenia and potentially one or more other conditions characterized by cognitive impairment. TC-5619 modulates the activity of the †7 NNR. We are currently conducting a Phase 1 single rising dose clinical trial of TC-5619 and plan to initiate a Phase 1 multiple rising dose clinical trial of TC-5619 in the second quarter of 2008. Following our completion of Phase 1 clinical development and a Phase 2 clinical proof of concept trial of TC-5619, AstraZeneca has the right to license TC-5619 for any or all of schizophrenia and various conditions characterized by cognitive impairment on terms specified in our agreement.

• TC-5214. TC-5214 is one of the two enantiomers of mecamylamine hydrochloride. Enantiomers are mirror images of each other that have the same chemical but potentially different biological properties and together form a chemical mixture known as a racemate. TC-5214 inhibits the activity of various NNR subtypes, including the †4ß2 NNR. We are currently developing TC-5214 as an augmentation treatment for major depression. We initiated a Phase 1 single rising dose clinical trial of TC-5214 in healthy volunteers in the first quarter of 2008.

In 2006, we completed a Phase 2 clinical trial of the racemate mecamylamine hydrochloride as an augmentation treatment to citalopram hydrobromide, a commonly prescribed treatment for depression marketed as Celexa in the United States, in patients who did not respond adequately to first-line treatment with citalopram. We refer to this treatment combination as TRIDMAC. In our preclinical evaluation, TC-5214 has exhibited a more favorable overall safety and efficacy profile than mecamylamine. We have no current plans to conduct further clinical development of mecamylamine and intend instead to pursue the development of TC-5214.

• TC-2216. Our depression and anxiety program also includes the novel small molecule TC-2216. TC-2216 inhibits the activity of the † 4ß2 NNR. We completed a Phase 1 single rising dose clinical trial of this product candidate in the first quarter of 2008. We may in the future elect to develop one of the enantiomers of TC-2216 in lieu of further development of TC-2216. However, based on our anticipated development of TC-5214 and our current budget management plans, we do not expect that we will conduct further clinical development of TC-2216 or either of its enantiomers in 2008.

• TC-6499. TC-6499 is novel small molecule that we plan to develop as a treatment for neuropathic pain. TC-6499 modulates the activity of the †4ß2 NNR. We initiated a Phase 1 single rising dose clinical trial of TC-6499 in the fourth quarter of 2007. TC-6499 is subject to a contingent future option of GlaxoSmithKline under the terms of our alliance

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Targacept Initiates Clinical Development of TC-5214 as Augmentation Therapy for Major Depressive Disorder

Winston-Salem, North Carolina

March 17, 2008

Targacept, Inc. (NASDAQ: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics (TM), today announced that it has initiated a Phase 1 clinical trial of TC-5214. Targacept is developing TC-5214 as an augmentation therapy for major depressive disorder (MDD). A Phase 2 clinical proof of concept trial is planned for later in 2008.

The Phase 1 trial, which is being conducted in the United States, is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of TC-5214 in healthy volunteers. TC-5214 is the S(+) enantiomer of the racemate mecamylamine hydrochloride, a broad spectrum NNR antagonist. In preclinical studies, TC-5214 has exhibited a better overall safety and efficacy profile than mecamylamine.

“We are delighted by the entry of TC-5214 into the clinic and enthusiastic about its strong therapeutic potential,” said J. Donald deBethizy, Ph.D., Targacept’s President and Chief Executive Officer. “The NNR mechanism represents an exciting new paradigm in the development of treatments for depression, a particularly critical health issue that demands a novel therapeutic approach. The positive results across multiple endpoints in our TRIDMAC trial underscore the potential for success in future trials of TC-5214.”

Targacept previously conducted a Phase 2 trial of racemic mecamylamine in 184 patients with major depressive disorder who did not respond adequately to first-line treatment with the selective serotonin reuptake inhibitor citalopram. In that trial, known as the TRIDMAC (TM) trial, patients whose continued citalopram treatment was augmented with racemic mecamylamine showed greater improvement on symptoms of depression than patients who received continued citalopram treatment and placebo. A poster presentation of the results of the TRIDMAC trial will be accessible from the TC-5214 page in the Product Pipeline section on Targacept’s website, www.targacept.com, until at least June 30, 2008

[Erbse1]

Milestones 2008 2009

[Erbse1]

Initial Phase 2 Trial of a Nicotinic Agonist in Schizophrenia.

Freedman R, Olincy A, Buchanan RW, Harris JG, Gold JM, Johnson L, Allensworth D, Guzman-Bonilla A, Clement B, Ball MP, Kutnick J, Pender V, Martin LF, Stevens KE, Wagner BD, Zerbe GO, Soti F, Kem WR.
Objective Nicotinic acetylcholine receptors are possible therapeutic targets for schizophrenia, as shown by neurobiological and molecular evidence for deficiencies in expression of alpha(7)-nicotinic receptors. Patients' heavy smoking suggests attempted self-medication through this mechanism. The agent 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A) is a partial alpha(7)-nicotinic agonist and can be taken orally. A phase 1 trial showed evidence for cognitive enhancement in schizophrenia. Method Thirty-one subjects with schizophrenia received DMXB-A at two different doses and placebo for periods of 4 weeks in a three-arm, two-site, double-blind, crossover phase 2 trial. The MATRICS Consensus Cognitive Battery assessed cognitive effects, and the Scale for the Assessment of Negative Symptoms (SANS) and Brief Psychiatric Rating Scale (BPRS) assessed clinical effects. Subjects continued their current antipsychotic drug during the trial and were nonsmokers. Results There were no significant differences in the MATRICS cognitive measures between DMXB-A and placebo over the three treatment arms, but the patients experienced significant improvement at the higher DMXB-A dose on the SANS total score and nearly significant improvement on the BPRS total score. Improvement was most notable on the SANS anhedonia and alogia subscales. Examination of the first treatment arm showed effects of DMXB-A on the attention/vigilance and working memory MATRICS domains, compared to baseline. Five subjects developed mild tremor, and nearly half had mild nausea while taking DMXB-A. Conclusions DMXB-A, a nicotinic agonist that activates alpha(7)-nicotinic receptors, improved clinical ratings of negative symptoms that are generally resistant to treatment with dopamine antagonist antipsychotic drugs. The clinical utility of this treatment is not yet determined.

[Erbse1]

Targacept Announces Designation of Lead Compound in Smoking Cessation Program
Monday May 5, 8:55 am ET
Triggers Milestone Payment from GlaxoSmithKline


WINSTON-SALEM, N.C.--(BUSINESS WIRE)--Targacept, Inc. (NASDAQ:TRGT - News), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics (TM), today announced the designation of a lead compound in its smoking cessation program, triggering a $500,000 milestone payment under its alliance agreement with GlaxoSmithKline (GSK).

“We are delighted to have successfully leveraged our expertise in NNRs to bring forward a novel compound for smoking cessation, an area that is not only a major healthcare need but also where application of the NNR mechanism has been validated commercially,” said J. Donald deBethizy, President and CEO of Targacept. “Emerging science has made the promise of NNR-targeted compounds as smoking cessation aids increasingly evident. It is important for a smoking cessation aid to specifically target the areas of the brain that serve as pathways for addiction, while addressing limitations of currently available products by minimizing unwanted side effects.”

Neuronal nicotinic receptors (NNRs) are a class of proteins in the nervous system that modulate the levels of key chemical messengers, such as dopamine. Nicotine’s addictive effects have been linked to over-stimulation of dopamine release in brain regions involved in feelings of reward and pleasure. Various NNR subtypes modulate dopamine release in these pathways and represent optimal targets for therapeutic intervention. Compounds that can normalize the activity of these NNR subtypes have the potential to decrease the rewarding effects of nicotine and, as a result, the desire to smoke.

In July 2007, Targacept and GSK entered into a strategic alliance pursuant to which Targacept would utilize its proprietary Pentad (TM) drug discovery technology to discover novel small molecule product candidates that target specified NNR subtypes in five therapeutic areas -- pain, smoking cessation, addiction, obesity and Parkinson’s disease. GSK is participating in the alliance through its Center of Excellence for External Drug Discovery.

Statistics from the Centers for Disease Control and Prevention indicate that tobacco use remains the leading preventable cause of death in the United States, causing approximately 438,000 premature deaths each year. Datamonitor projects that the global prescription market for smoking cessation therapies will be as much as $4.6 billion by 2016.

[Erbse1]

Der erste Teil der AZD3480 Studie bei Alzheimer ist geschafft. Das ging aber fix. Bin gespannt, wann die Ergebnisse präsentiert werden.Ich glaube, ich habe mal als Termin Ende August gehört.

Proof of Concept Study of Cognitive Improvement in Patients With Alzheimer's Disease (Sirocco)

http://www.clinicaltrials.gov/ct2/show/NCT00501111?term=azd3…

Die Studie zu kognitiven Defiziten bei Schizophrenie ist noch aktiv.

[Erbse1]

Neue kleine ADHD Studie mit AZD3480 gestartet. Targacept und AstraZeneca haben ohne Veröffentlichung eine Studie gestartet. Ergebnisse sollen Anfang 2009 vorliegen. Kommt etwas überraschend jetzt so plötzlich ohne Vorankündigung. Vielleicht bietet sich hier ein ganz neues Betätigungsfeld an. So weit ich weiß, hat sich AstraZeneca auch bei ADHD die Rechte von Targacept gesichert.

Exploratory Trial of AZD3480 for Adult Attention-Deficit/Hyperactivity Disorder (ADHD)

Purpose
The main goal of this placebo controlled exploratory study is to determine the effects of two weeks of AZD3480 (TC-1734) treatment on the clinical and cognitive symptoms of ADHD.

[Erbse1]

Antwort auf Beitrag Nr.: 34.165.307 von Erbse1 am 24.05.08 17:08:21

Hier jetzt die Bestätigung der ADHD Studie durch Targacept

Targacept and AstraZeneca Initiate Clinical Trial of AZD3480 in Adult ADHD

Winston-Salem, North Carolina

June 10, 2008

Targacept, Inc. (NASDAQ: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics (TM), today announced the initiation of a Phase 2 clinical trial of AZD3480 (TC-1734) in adults with Attention Deficit/Hyperactivity Disorder, or ADHD.

“In our previous clinical trials of AZD3480, the compound has demonstrated compelling attentional effects,” said J. Donald deBethizy, Ph.D., President and Chief Executive Officer of Targacept. “We expect this well-designed pilot study to provide valuable insight that will facilitate future development planning.”

The primary objective of the double blind, placebo controlled, crossover trial is to assess the efficacy of two different dose strengths of AZD3480 in adult subjects diagnosed with ADHD. The crossover trial design provides for each subject to serve as its own control by receiving both dose strengths of AZD3480 as well as placebo, with the treatment periods separated by a washout period. The trial, which is planned to enroll 24 subjects, is being conducted at Fletcher Allen Health Care, an affiliate of the University of Vermont College of Medicine, under the direction of Drs. Paul Newhouse and Alexandra Potter.

Targacept and AstraZeneca are collaborating on the execution of the trial, with Targacept responsible for managing and funding the trial and AstraZeneca responsible for providing the clinical trial materials and communicating with regulatory authorities.

Clinical studies of AZD3480 previously conducted in approximately 540 subjects, including both healthy volunteers and cognitively impaired older adults, indicate the beneficial effects of AZD3480 on cognitive function generally and attention and memory in particular. AZD3480 is currently being evaluated in two Phase 2b clinical trials, one in mild to moderate Alzheimer's disease (the “Sirocco” trial) and one in cognitive dysfunction in schizophrenia (the “HALO” trial). These trials, which are together planned to enroll approximately 925 patients, are being conducted by AstraZeneca and are expected to be completed in the second half of 2008.

[Erbse1]

Kleine Zusammenfassung des NeuroInvestor zu Targacept aus dem letzten Börsenbrief.

Targacept: Commentary

(from July/August 2008 NI)

Partner AstraZeneca should report the AD and schizophrenia Phase IIb trial data for TC-1734 before the end of this year. As we predicted, Targacept and AstraZeneca folded in TC-5619 for schizophreniform cognition, with a $2 million milestone payment going to Targacept. TC-1734 is now going to be also tested in ADHD, following Abbott/NeuroSearch's successful Phase II trial with their nicotinic alpha4beta2 drug. Targacept is enthused about its mecamylamine enantiomer TC-5214, which offers patent protection and, they believe, potential as both an adjunct antidepressant (being tested therein first) and as a monotherapy. Targacept's view is that the compound will offer very rapid relief of anxiety symptoms, which may provide patients with a sense of improvement as the slower-to-develop depression effects per se then gradually emerge. GSK recently paid a milestone on a second pain compound, and Targacept has identified a lead for smoking cessation.

Quelle: http://www.neuroinvestment.com/NewComTargacept.html

[Erbse1]

Targacept Initiates Phase 2b Clinical Trial of TC-5214 as Augmentation Treatment in Major Depressive Disorder

Winston-Salem, North Carolina

July 21, 2008

Targacept, Inc. (NASDAQ: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics (TM), today announced that it has initiated a Phase 2b clinical trial of TC-5214 as an augmentation therapy in subjects with Major Depressive Disorder (MDD). TC-5214 is a broad spectrum neuronal nicotinic receptor (NNR) antagonist and represents a promising new mechanism in development for the treatment of MDD.

“The millions of patients suffering from depression who do not respond well to the currently available first-line therapies need help,” said Dr. Madhukar H. Trivedi, Professor and the Director of the Mood Disorders Research Program and Clinic at the University of Texas Southwestern Medical Center at Dallas and one of the principal investigators in the National Institute of Mental Health’s large-scale STAR*D study. “There is a great unmet medical need for effective second and third line treatments with novel mechanisms of action to augment existing therapies and improve clinical outcomes for these patients. I am very enthusiastic about the potential for NNR-targeted compounds and other novel mechanisms to serve this need.”

The design of the Phase 2b trial of TC-5214 includes two phases. In the first phase, subjects diagnosed with MDD will receive citalopram hydrobromide, a selective serotonin reuptake inhibitor (SSRI), for eight weeks to determine the extent of therapeutic response. Subjects who have not responded well based on predefined criteria would be randomized into the double blind second phase of the trial and receive either TC-5214 or placebo, together with continued citalopram therapy, for an additional eight weeks. It is expected that approximately 560 subjects will participate in the first phase of the trial and approximately 220 subjects will be randomized into the second phase of the trial. The primary endpoint of the trial is change from baseline during the second phase of the trial as measured by the Hamilton Depression Rating Scale. The trial will also collect information on a variety of secondary safety and efficacy measures. The trial is planned to be conducted at sites in the United States and India.

“The initiation of this Phase 2b clinical trial, just four months after TC-5214 initially entered the clinic, reflects not only our enthusiasm for its therapeutic promise but also our ability to execute against a very aggressive development plan,” said J. Donald deBethizy, Ph.D., President and Chief Executive Officer of Targacept. “We believe that the favorable preclinical profile of TC-5214, combined with the positive results from our previous Phase 2 clinical trial of mecamylamine as an augmentation treatment for MDD, bode well for TC-5214’s potential for clinical success.”

About TC-5214
It is well known that depressive symptoms can result from an overstimulation of NNRs and other receptors in the brain that are activated by the neurotransmitter acetylcholine. Accordingly, compounds capable of inhibiting the activity of these overstimulated receptors, known as antagonists, may be expected to have antidepressant effects. In a prior Phase 2 clinical trial conducted by Targacept, subjects with MDD whose treatment with citalopram was augmented with mecamylamine hydrochloride showed greater improvement on symptoms of depression than subjects who received continued citalopram treatment and placebo.

TC-5214 is the S(+) enantiomer of mecamylamine hydrochloride. TC-5214 has exhibited an overall therapeutic profile superior to mecamylamine in preclinical models of depression and anxiety (Lippiello et al., accepted for publication in CNS Neuroscience & Therapeutics), a finding consistent with laboratory studies showing TC-5214 to more effectively inhibit the activity of the alpha4beta2 NNR.

About MDD
According to The National Institute of Mental Health, MDD is the leading cause of disability in the United States for people between the ages 15 and 44. The NIMH estimates that approximately 14.8 million American adults suffer from MDD.

The Sequenced Treatment Alternatives to Relieve Depression, or STAR*D, study undertaken by the National Institute of Mental Health between 2001 and 2006 showed the inadequacy of currently available therapies for MDD. In the first phase of the STAR*D study, approximately 2,800 persons with MDD were given citalopram for 12 to 14 weeks. Only about one-third of the participants reached remission and about 10-15 percent more responded, but did not reach remission. The second phase of the STAR*D study evaluated the effects of augmentation with a new medication or switching to a different treatment for participants who did not respond or only responded partially to citalopram. Approximately one in four of these participants reached remission. These findings have been cited as highlighting the need for more broadly effective antidepressant treatments

[Erbse1]

Die Studie für kognitive Störungen bei Schizophrenie hat die Rekrutierung beendet.

Proof of Concept Study of Cognitive Improvement in Patients With Schizophrenia (HALO)

This study is ongoing, but not recruiting participants.

Soweit ich weiß ist Targacept auf diesem Gebiet am weitesten fortgeschritten. Bisher gibt es für dieses Gebiet noch keine getestete Anwendung. Die Auswertung dürfte noch einige Zeit dauern, doch ich bin sehr gespannt auf die Ergebnisse, da hier gleichzeitig eine Wechselwirkung mit den Psychosemedikamenten eintritt. Leider weiß ich auch nicht, welche Auswirkung das im Ergebnis haben könnte. Also lassen wir uns mal überraschen.

Warscheinlich werden nächsten Monat die Ergebnisse zu Alzheimer Studie 2b mit AZD 3480 veröffentlicht.

Grüße
Erbse

[Erbse1]

Kleine Zusammenfassung der Halbjahreszahlen, TC-5619 ist jetzt erstmal für kognitive Defizite geplant

Ongoing Phase 2b Clinical Trials of AZD3480 (TC-1734)

In addition to reporting its financial results, Targacept announced that it currently expects to report top-line results from the Phase 2b clinical trial of AZD3480 (TC-1734) being conducted by AstraZeneca in mild to moderate Alzheimer's disease (the "Sirocco" trial) in September 2008. Targacept also confirmed that the Phase 2b clinical trial of AZD3480 (TC-1734) in cognitive dysfunction in schizophrenia (the "HALO" trial) is fully enrolled and remains on track to be completed by AstraZeneca by the end of 2008.

Recent Highlights

AstraZeneca Collaboration and Cognitive Disorders

Initiated an exploratory Phase 2 clinical trial of AZD3480 (TC-1734) in adults with attention deficit/hyperactivity disorder in collaboration with AstraZeneca;

Completed a Phase 1 single rising dose clinical trial in which TC-5619 was generally well tolerated at a dose at least 100 times greater than doses expected to have positive effects on cognition in humans based on Targacept's preclinical work; TC-5619, a highly-selective alpha7 NNR-targeted product candidate, is planned for development for cognitive dysfunction in schizophrenia and potentially one or more other conditions characterized by cognitive impairment, and Targacept plans to initiate a Phase 1 multiple rising dose clinical trial in the third quarter of 2008;
Depression

Completed the dosing phase of a Phase 1 single rising dose clinical trial of TC-5214;

Initiated a Phase 2b clinical trial of TC-5214, the S+ enantiomer of mecamylamine hydrochloride and a broad spectrum NNR antagonist, as an augmentation therapy in subjects with major depressive disorder who do not respond or who only partially respond to first-line treatment with the marketed antidepressant citalopram hydrobromide;

GlaxoSmithKline Alliance and Pain

Completed a Phase 1 single rising dose clinical trial of TC-6499, an alpha4beta2 NNR-targeted product candidate planned for development for neuropathic pain, and plan to initiate additional Phase 1 clinical development in the third quarter of 2008;

[Erbse1]

Das trifft Targacept sehr hart. Mal sehen, was sie hier weiter planen. Schade eigentlich, hörte sich sehr erfolgversprechend an.


Monday September 15, 4:47 pm ET

AstraZeneca, Targacept say results of Alzheimer's drug study are inconclusive

WILMINGTON, Del. (AP) -- Drugmaker AstraZeneca Inc. and drug developer Targacept Inc. on Monday announced disappointing results for a midstage trial of a treatment the companies are developing for Alzheimer's disease.

The companies said results for the study of the drug candidate, called AZD3480, were inconclusive, because the differences between AZD3480 and donepezil weren't statistically significant. Donepezil, sold under the brand name Aricept, is already marketed for Alzheimer's treatment.

The study was also affected by an improvement in brain function among the group of patients receiving a placebo, or dummy pill.

In the trial, 567 patients with mild to moderate Alzheimer's were given either AZD3480, donepezil or a placebo for 12 weeks. The patients then were judged by accepted clinical measures of cognitive function.

AstraZeneca said it expects to decide the future of the drug's development in December.

AZD3480 is also in midstage testing for cognitive problems tied to schizophrenia, and as a treatment for attention deficit hyperactivity disorder.

[Erbse1]

Antwort auf Beitrag Nr.: 35.129.417 von Erbse1 am 16.09.08 13:42:02

Kommentar des Börsenbriefes NeuroInvestor

Targacept: Commentary

(9/16/08 comment on Phase IIb Alzheimer's data)

Targacept/AstraZeneca's TC-1734/AZD-3480 underwhelmed with its Phase IIb Alzheimer's results, topline data released by partner AstraZeneca. It did not definitively fail, even though it missed its primary endpoint, but even when looking at the silver lining, it does appear expectations for this drug in dementia will have to be ramped down. Here are some of the interesting findings and our conjectures:
1) That confounding placebo effect. The placebo group did not show the modest decline one would expect over just three months, indeed they improved. And of course, the safety/tolerability profile of the placebo was outstanding. In retrospect, AZ may/should kick themselves for not running a six month trial, where such an effect is likely to diminish.
2) The benefit of AZD3480 did not outshine Aricept in any consistent way, though it did outperform Aricept on the ADS-CGIC. That is a caregiver/prescriber assessment of patient outcome, which to some degree represents a shot at capturing real-life functional gains that do not translate well into cognitive test scores, but this kind of data is also more subjective and 'squishy'.
3) The report of benefit on the blunt-instrument MMSE is not entirely reassuring, we would have hoped to see some trend on the more detailed CDR, and perhaps something will yet come from more detailed analysis of the several domains assessed.
4) Aricept did not perform any better, and indeed was worse on the ADS-CGIC. It is a reminder that even this lucrative gold standard drug doesn't present all that high a hurdle to match, and matching it is a consolation prize at best.
5) The patient population in this large (567 patients were dosed, at 84 sites!) trial was from Europe and Canada. We will be curious to see what proportion was enrolled in Eastern Europe, where the quality control and experience that can be assumed in clinical trial execution is not as assured, but rapid enrollment is. Just as we have some qualms about Medivation's reliance upon 181 Russian patients, we wonder if there was any divergence associated with those trial sites.
6) There is a modest signal of effect here, but based on what is known thus far, one would have to project a drug which is as effective, but probably not superior to, Aricept in terms of efficacy, but has better tolerability. Whether that will be enough to persuade AstraZeneca to go into Phase III (which would have to be at least six months of treatment) remains to be seen.
7) This raises the stakes on the schizophreniform cognition Phase IIb results, which will be out in December, the same month that AstraZeneca has to decide whether or not they are going to go into Phase III for AD or schizophrenia, and pay the requisite milestone to Targacept. ADHD data will be out in early 2009, but AZ will have to make its decision before then.

8) While comparing studies is a dicey proposition, it is worth noting that Memory Pharma's nicotinic alpha 7 drug (MEM3454), which has a different target than AZD3840, which is an alpha4beta2 modulator, produced a statistically significant effect on the CDR in just eight weeks. Interestingly, both drugs showed an inverted-U response curve, with the mid-dose performing best. This leaves open the question of which NNR target is optimal for AD, and what about the pharmacokinetics of these drug/receptor interactions lead to this dimunition of effect with higher doses.

[Kostolany4]

Seit der Ankündigung des neuen Medikaments hat sich die Aktie gefünftelt. Das kann man nicht mehr durch "Sell on good news" erklären. Was steckt da dahinter ?

In der Werbekampagne eines Börsenbriefes ist davon die Rede, daß sich der Kurs ver-86-fachen soll.

[Erbse1]

Antwort auf Beitrag Nr.: 36.105.293 von Kostolany4 am 28.11.08 16:28:49

Hallo Kostolany,

die Phase2 bei Alzheimer lief alles andere als positiv,
der Gesamtmarkt läuft beschissen
Viele zweifeln, ob die Phase 2 bei kognitive Defizite bei Schizophrenie gut laufen.

Diese Kursziele gelten halt nur, wenn die Testphasen auch positiv verlaufen, jetzt glaubt halt keiner mehr an den Erfolg.

Grüße
Erbse

[Erbse1]

Antwort auf Beitrag Nr.: 36.105.476 von Erbse1 am 28.11.08 16:41:54

Das schaut jetzt gar nicht mehr gut aus für Targacept.

AstraZeneca and Targacept Announce Top-Line Results from Phase IIb Study of AZD3480 in Cognitive Dysfunction in Schizophrenia
Monday December 8, 2008, 4:05 pm EST

& WINSTON-SALEM, N.C.--(BUSINESS WIRE)--AstraZeneca (NYSE: AZN - News) and Targacept, Inc. (NASDAQ: TRGT - News) today announced top-line results from a Phase IIb clinical trial of AZD3480 (TC-1734) conducted by AstraZeneca in cognitive dysfunction in schizophrenia (CDS), known as the HALO trial.


AZD3480 did not meet the trial’s criteria for statistical significance on the primary endpoints, improvement on various cognitive domains measured by the IntegNeuro computerized test battery. AZD3480 was generally well tolerated in the study. AstraZeneca and Targacept do not expect to progress AZD3480 into Phase III studies for CDS.

In addition to the HALO trial, AstraZeneca and Targacept previously announced top-line results from a Phase IIb study of AZD3480 in mild to moderate Alzheimer's disease, known as the Sirocco trial, and are currently evaluating AZD3480 in a Phase II exploratory study in attention deficit/hyperactivity disorder (ADHD) in adults. A decision by AstraZeneca with respect to potential further development of AZD3480 in Alzheimer’s disease or ADHD is now expected in the first half of 2009, pending completion of the adult ADHD study and other ongoing evaluations.

“While this trial outcome did not meet our objectives, we continue to pursue medicines that target neuronal nicotinic receptors (NNRs) with Targacept to treat cognitive disorders,” said Bob Holland, Vice President and Head of the Neuroscience Therapy Area, AstraZeneca.

Targacept and AstraZeneca also announced that the lead compound arising out of the parties’ preclinical research collaboration is poised to enter the clinic. AstraZeneca plans by the end of 2008 to initiate a Phase I trial of AZD1446 (TC-6683), a product candidate selective for the alpha4beta2 NNR. Under the terms of the parties’ collaboration agreement, AstraZeneca has agreed to make a $2.0 million milestone payment to Targacept.

“We are obviously disappointed that AZD3480 did not meet our goals in the HALO trial,” commented J. Donald deBethizy, Ph.D., President and Chief Executive Officer of Targacept. “We thank AstraZeneca for its commitment to AZD3480 and its investment in this pioneering work in an emerging area considered to be critical in the treatment of patients with schizophrenia. We look forward to continuing our cognition-focused collaboration with AstraZeneca.”

Study Design

The Phase IIb HALO trial was conducted by AstraZeneca under the terms of an exclusive global license and research collaboration agreement. The trial was a multi-center, randomized, double blind, placebo controlled, dose-finding study conducted at approximately 70 enrolling sites in the United States and Canada. Subjects (n = 445) between 18 and 55 years of age who were active smokers and taking medication from the class of drugs known as atypical anti-psychotics were randomly assigned to one of three dose groups of AZD3480 or to placebo and dosed over a 12-week period. The primary endpoints of the trial were change from baseline after 12 weeks on various domains of cognition as measured by the IntegNeuro computerized test battery1.

[Buddah]

'Memory pill' that could help with exam revision could be available soon
http://www.telegraph.co.uk/news/newstopics/howaboutthat/4283…

[Erbse1]

Positive Daten bei ADHD

Targacept Announces Positive Top-Line Results from Phase II Study of AZD3480 in Adult ADHD
Winston-Salem, NC

May 11, 2009



Targacept, Inc. (NASDAQ: TRGT) today announced preliminary results showing that AZD3480 (TC-1734) met the primary outcome measure in a Phase II clinical study in adults with attention deficit/hyperactivity disorder (ADHD).

In the study, adult subjects received in random order daily doses of 5mg of AZD3480, 50mg of AZD3480 and placebo, each for two weeks with the dosing periods separated by a three-week washout period. At 50mg AZD3480, subjects showed statistically significant (p < .01) improvement in symptoms of ADHD as measured by the study’s primary outcome measure, total symptom score on the Conners Adult ADHD Rating Scale – Investigator Rating (CAARS-INV). Data from the study on CAARS-INV are shown in the table below.

Completed Subjects Pre-Treatment Mean (Standard Deviation) Post-Treatment Mean (Standard Deviation) Mean Change
(Standard Deviation)

placebo 24 37.7 (5.45) 36.9 (5.20) 0.8 (5.33)

5mg AZD3480
23 39.6 (5.36) 34.9 (5.24) 4.7 (5.30)
50mg AZD3480 24 40.3 (5.40) 33.1 (5.34) 7.2 (5.37)


Statistically significant results were also achieved at 50mg AZD3480 on a number of secondary outcome measures in the study, including Stop Signal Reaction Time, a computerized assessment of behavioral inhibition, which is a core cognitive deficit of ADHD.

AZD3480 was well tolerated in the study, and there were no serious adverse events.

“In this study AZD3480 positively affected the core symptoms of adult ADHD patients. The results showed a consistent effect between improvements in clinical symptoms and a core cognitive deficit. Additionally, we saw improvement after just one week of treatment with the 50mg dose of AZD3480 and then continued improvement at the end of the second week,” commented Paul A. Newhouse, M.D., Professor of Psychiatry and Director, Clinical Neuroscience Research Unit and Brain Imaging Program, University of Vermont College of Medicine, and the principal investigator for the study.

“These results further our belief in AZD3480’s potential to benefit patients and reinforce our longstanding commitment to the neuronal nicotinic receptor mechanism. AZD3480 has now been studied in over 1,350 subjects providing us and AstraZeneca with substantial data,” said J. Donald deBethizy, Ph.D., President and Chief Executive Officer of Targacept.

“We are encouraged by the preliminary results of the study presented to us. There is a compelling need to develop novel, well-tolerated, non-stimulant medicines to meet the needs of patients with ADHD,” said Bob Holland, Vice President Neuroscience and Head of the Neuroscience Therapy Area, AstraZeneca. “We look forward to completing a full analysis of the data set and then making our decisions around the future development of this compound.”

Next Steps

Analyses of the full dataset from the study remain ongoing. AstraZeneca and Targacept plan to present and publish more detailed results from the study at a future scientific meeting.

AstraZeneca is expected to determine whether to conduct further development of AZD3480 in ADHD and/or Alzheimer's disease in the second quarter of 2009.
Study Design

Double blind, placebo controlled, crossover study conducted at Fletcher Allen Health Care, an affiliate of the University of Vermont College of Medicine.
Subjects were between the ages of 18 and 65, male and female, non-smokers, diagnosed with ADHD based on DSM-IV criteria and had a baseline score of at least 4 on the Clinical Global Impression – Severity scale.
Efficacy dataset included 24 completed subjects.
Each subject received in random order 5mg of AZD3480, 50mg of AZD3480 and placebo, in each case daily for two weeks, with the dosing periods separated by a three-week washout period designed to minimize carryover effects. As a result, each subject served as his or her own control.
The primary outcome measure was the change in total symptom score on the Conners Adult ADHD Rating Scale – Investigator Rating (CAARS-INV) following two weeks dosing with AZD3480 as compared to two weeks dosing with placebo.

Quelle:http://www.targacept.com/wt/page/pr_1242008964

[Erbse1]

Antwort auf Beitrag Nr.: 37.144.196 von Erbse1 am 11.05.09 14:26:25

Targacept Announces Decision by AstraZeneca to Advance AZD3480 Program in ADHD

- AstraZeneca to Develop 2nd NNR Therapeutic (AZD1446) for Alzheimer’s Disease -Targacept to Receive $10 Million Milestone Payment

Winston-Salem, North Carolina

July 08, 2009

Targacept, Inc. (NASDAQ: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics (TM), today announced that AstraZeneca has informed Targacept that it plans to conduct further development of AZD3480 (TC-1734) for attention deficit/hyperactivity disorder (ADHD) and has agreed to make a $10 million milestone payment to Targacept.

AstraZeneca also confirmed plans to continue development of AZD1446 (TC-6683) for Alzheimer’s disease. AZD1446, which is currently in Phase 1, was discovered in the parties’ ongoing research collaboration. For Alzheimer’s disease, development of AZD1446 has been prioritized by AstraZeneca over further development of AZD3480. AZD3480 and AZD1446 are selective alpha4beta2 NNR agonists.

“We continue to be enthusiastic about neuronal nicotinic receptors as a promising new mechanism in the treatment of multiple cognitive disorders,” said Bob Holland, Vice President and Head of the Neuroscience Therapy Area, AstraZeneca. “We believe the therapeutic profile of AZD3480, a non-stimulant, may be an important advance for treating patients with ADHD and we also remain positive about the potential of NNR agonists to treat Alzheimer’s disease.”

AstraZeneca has presented Targacept with preliminary plans for a robust development program for AZD3480 in ADHD, including clinical studies to include both younger subjects and adults.

Under the terms of an amendment to the parties’ collaboration agreement, AstraZeneca has agreed to make the $10 million milestone payment described above and Targacept is eligible to receive a lower aggregate milestone stream for AZD3480 if ADHD is the only target indication for which AZD3480 is developed further. Targacept remains eligible to receive over $100 million if development, regulatory and first commercial sale milestones are achieved for AZD3480 only in ADHD, as well as stepped double-digit royalties on any future sales of AZD3480 in any indication. Targacept also continues to be eligible to receive future payments upon the achievement of milestone events for AZD1446 and royalties on any future sales of AZD1446.

“We appreciate the efforts and dedication of our colleagues at AstraZeneca as we work together to develop and deliver the promise of NNR Therapeutics to patients affected by cognitive disorders like ADHD and Alzheimer’s disease,” said J. Donald deBethizy, Ph.D., President and Chief Executive Officer of Targacept. “In addition to AZD3480 and AZD1446, we remain enthusiastic about the breadth and pharmacological diversity of our portfolio. With our pipeline, strong alliances and a cash runway that we expect to fund our operations for at least the next two years, we are well positioned to execute our business plan.”

[Erbse1]

Aus aktuellem Anlass noch mal einen Überblick von der Targacept Pipeline. Eine Alternative zu den herkömmlichen ADHD Medikamenten mit den Nebenwirkungen wäre schon wünschenswert. Mal sehen was draus wird.
Grüße
Erbse

[Erbse1]

Volltreffer

Targacept’s TC-5214 Achieves All Primary and Secondary Outcome Measures in Phase 2b Trial as Augmentation Treatment for Major Depressive DisorderHigh Statistical Significance Achieved on HAM-D Scale (p < 0.0001) in 265 Patients

Winston-Salem, North Carolina

July 15, 2009

Targacept, Inc. (NASDAQ: TRGT) today announced positive top-line results from a double blind, placebo controlled, flexible dose Phase 2b clinical trial of TC-5214 as an augmentation (add-on) treatment for major depressive disorder, or MDD, in subjects who did not respond adequately to first-line treatment with citalopram alone. The result on the primary outcome measure for the trial, mean change between treatment (TC-5214 + citalopram) and placebo (placebo + citalopram) from baseline on the Hamilton Rating Scale for Depression-17, or HAM-D, was highly statistically significant in favor of TC-5214 (p < 0.0001) on an intent to treat basis. The results on all of the trial’s secondary efficacy measures, including assessments of depression, irritability, disability, cognition, severity of illness and global improvement, were also highly statistically significant in favor of TC-5214 on an intent to treat basis.

“The magnitude and consistency of the effect of TC-5214 seen in this trial could represent a major breakthrough for patients with depression,” said Dr. Madhukar H. Trivedi, Professor and the Director of the Mood Disorders Research Program and Clinic at the University of Texas Southwestern Medical Center at Dallas, one of the principal investigators for the trial and Co-Principal Investigator in the National Institute of Mental Health’s large-scale STAR*D study. “It is particularly compelling that the superiority of TC-5214 as augmentation to citalopram over citalopram alone was first seen after only two weeks and grew steadily over the trial’s last six weeks, culminating in remission for twice as many subjects in the TC-5214 group.”

TC-5214 exhibited a favorable tolerability profile in the trial. The most frequent adverse events were headache, dizziness and constipation. There was no clinically significant difference between the dose groups in discontinuations due to adverse events. There was one serious adverse event in the trial considered by the investigators to be related to study drug (citalopram and/or TC-5214), a seizure experienced by a study subject.

“The strong results from this Phase 2b augmentation trial support the potential of TC-5214 to provide much needed help for the millions of depressed patients who do not respond adequately to currently available therapies,” said Geoffrey C. Dunbar, M.D., Targacept’s Vice President, Clinical Development and Regulatory Affairs. “This is the second time our clinical trials have shown antidepressant effects of this NNR mechanism. We are particularly enthusiastic about the finding in this study on irritability, which is a core symptom of MDD that is often difficult to treat.”

Next Steps
Targacept plans to present detailed results from the Phase 2b trial of TC-5214 at the Society for Neuroscience meeting scheduled for October 2009 in Chicago, Illinois.

Targacept is active in discussions with multiple pharmaceutical companies with the goal of identifying a strategic partner to assist in the global development and planned commercialization of TC-5214. Targacept expects Phase 3 clinical development to be initiated in the second quarter of 2010, following planned discussions with FDA and production of clinical trial material.

Study Design
The Phase 2b trial of TC-5214 as an augmentation treatment for MDD was a two-phase study conducted at 20 sites in India and three sites in the United States. In the first phase, 579 subjects with MDD received first-line treatment with citalopram hydrobromide for eight weeks, 20mg daily for the first four weeks and 40mg daily for the next four weeks. Citalopram, an approved treatment for MDD marketed in the United States as Celexa®, is from the drug class known as selective serotonin reuptake inhibitors. At the end of the eight weeks, subjects whose Montgomery-Asberg Depression Rating Scale score had improved less than 50 percent and was no lower than 17 and whose Clinical Global Impression - Severity of Illness score was no lower than 4 were considered partial or non responders and randomized into the double blind second phase of the trial.

In the double blind second phase, subjects continued their citalopram treatment and also received either add-on TC-5214 or add-on placebo for an additional eight weeks. The daily dosage of TC-5214 was initially 2mg and could be increased at the discretion of the investigator to 4mg and to 8mg based on tolerability and therapeutic response. The primary outcome measure for the trial was mean change between treatment (TC-5214 + citalopram) and placebo (placebo + citalopram) from double blind baseline as measured by HAM-D at week 16. The intent to treat dataset included 265 subjects in the second phase.

About TC-5214
It is well known that depressive symptoms can result from an overstimulation of NNRs and other receptors in the brain that are activated by the neurotransmitter acetylcholine. Accordingly, compounds capable of inhibiting the activity of these overstimulated receptors may be expected to have antidepressant effects. TC-5214 is a nicotinic channel blocker that has unique properties in modulating the alpha4beta2 NNR subtype.

[Erbse1]

Tageschart

[Erbse1]

Langfristbiotechchart:

[KillingJoke]

Antwort auf Beitrag Nr.: 37.577.034 von Erbse1 am 15.07.09 14:09:16

Hallo Erbse,

das Teil ist irre gelaufen. Hoch war bei 21.84 USD.
Ich finde es etwas sehr hoch.
Wo siehst Du jetzt noch Kurs-Potential von Targacept?

Gruss
KJ

[Erbse1]

Antwort auf Beitrag Nr.: 38.103.009 von KillingJoke am 02.10.09 13:21:30

Hallo KillingJoke,
bei Targacept habe ich einen schweren Fehler begangen. Bin nach den schlechten Ergebnissen bei ALzheimer und Kognitive Defizite bei Schizophrenie rausgegangen. Habe den Wiedereinstieg verpasst.

Ich hatte die zweite Reihe analysiert, habe sie aus irgendwelchen Gründen nicht mehr verfolgt. Das wäre sonst für mich ein Einstiegspunkt. Als die guten Ergebnisse kamen, hatte ich kein Geld mehr frei für eine Investition.
Eine Alternative bei ADHD hat gute Chancen, weil die herkömmlichen Mittel mit starken Nebenwirkungen behaftet sind.

Ich denke mal sie kriegen 10% von Astra Zeneca.

Der Rest ist schon bis auf Entzündungen auslizensiert.
Die Pipeline ist halt noch in sehr frühen Stadien. Habe auch die Patentlaufzeiten nicht mehr im Kopf. Vom Gefühl her würde ich nicht mehr reingehen. Lieber nach neuen Schätzchen suchen. Manchmal verpasst man auch ne Gelegenheit.

Grüße
Erbse

[Erbse1]

Hallo Killing Joke,
hier mal ein Schaubild der aktuellen Pipeline.



Es ist etwas früh bei Targacept eine genauere Bewertung abzugeben.

Aussichtsreich ist sicher die auslizensierte Anwendung ADHD. Targacept wird hier ca. 10% von AstraZeneca bekommen. Bei einem überlegenem Nebenwirkungsprofil könnten hier in etwa 100 Millionen $ für Targacept drin sein.

Etwas weiter fortgeschritten sind auch die Tests von TC-5214 bei Depression. Hier winken enorme Einnahmen. Mal sehen was bei einer Auslizensierung hier ausgehandelt wird. Bei den vorliegenden Phase 2 Ergebnissen dürfte wohl auch bald ein Partner präsentiert werden.

Das Anwendungsgebiet Kognitive Defizite bei Schizophrenie ist sehr komplex und schwer einzuschätzen. Unsicherheitsfaktoren sind hier die Psychopharmaka, die gegen diese Krankheit verschrieben werden. Jeder Wirkstoff hat auch einen anderen Einfluß auf die kognitive Leistungsfähigkeit. Theoretisch müßte man jeden Wirkstoff, der gegen Schizophrenie verschrieben wird, einzeln mit TC-5619 testen
Bei einem Medikament könnte TC-5619 positiv sein, bei einem anderem wiederum negativ. Sehr schwierig einzuschätzen.

Alzheimer mit AZD1446 in Phase 1 müßen wir abwarten. Mit AZD3480 konnte sie keine positiven Ergebnisse liefern. Doch die Konkurrenz ist riesig. Keine Ahnung, wer das Rennen macht. Über Alzheimer stelle ich keine Recherchen mehr an. Ist mir zu umfangreich. Bei einem Erfolg winken riesige Einnahmen.

Alle anderen Wirkstoffe sind vorklinisch und fast alle an GlaxoSmithKline auslizensiert. Vereinbarte Milestones sind 1,5 Milliarden $, aber nur bei einem Erfolg. Dazu kämen dann die Umsatzbeteiligungen in Höhe von ca. 10%.

Targacept ist im Augenblick mit ca. 500 Millionen $ bewertet. Auf lange Sicht und bei Erfolg hat Targacept sicher noch Potenzial. Leider habe ich den Wiedereinstieg verpasst. Schade, war eine Superchance. Ich gehe nicht mehr rein. Suche weiter nach erfolgversprechenden Kandidaten.

Grüße
Erbse

[KillingJoke]

Antwort auf Beitrag Nr.: 38.108.556 von Erbse1 am 03.10.09 09:20:36

Erbse,
wie immer super Zusammenfassung.
Danke.

[KillingJoke]

Antwort auf Beitrag Nr.: 38.103.009 von KillingJoke am 02.10.09 13:21:30

Hallo Erbse,

TRGT wird irgendwann richtig abschmieren, soviel ist (für mich) klar.
Die ersten Shortseller hatten Targacept allerdings schon bei 8,60 USD als überbewertet angesehen.
TRGT hat gestern bei 22.50 USD eine neues Allzeithoch markiert.
Marktkapitalisierung liegt bei 564,12 Mio. USD, dem steht ein Cash von 44 Mio USD gegenüber.
TRGT hat in den letzten 12 Monaten 17,8 Mio USD verbrannt.
Wenn ich die Pipeline gewichte um dass, was bei den Biotechs üblicherweise in die Hose geht, finde ich TRGT überbewertet.

Mein Kursziel lautet 12 USD.
(Wäre ja dann immer noch ein schöner Anstieg von 3 USD seit Vermeldung der Phase II Zwischeninformation vom Juli für TC-5214 bei Depression.)

Wir erinnern uns:
15.07.09
Anstieg von 3.06 USD auf 7.81 USD.
"Targacept said its drug candidate, called TC-5214, significantly improved symptoms of major depressive disorder for patients who did not respond to an older drug, Forest Laboratories Inc.'s Celexa. TC-5214 was better than a placebo at improving an overall depression measurement, as well as reducing depression, irritability and severity of illness, and leading to better cognition and overall improvement."

[Erbse1]

Hallo Killing Joke,

da könntest du Recht haben. Die größte Fantasie kommt wohl von TC-5214 als add on bei Depression. Dies könnte die Cash Situation bei einer Auslizensierung spürbar verbessern und ausbauen.
Hauptpluspunkte sind da wohl noch die sehr guten Partnerschaften mit AstraZeneca und GlaxoSmithKline. Damit dürfte Targacept nicht in finanzielle Nöte kommen und die Pipeline in Ruhe entwickeln.
Ich sehe auch nicht so viel kurzfristiges Potenzial. Zum Shorten wäre ich im Augenblick aber zu feige. Da gibt es im Augenblick Biotechs mit ähnlichen Erfolgsaussichten, die aber nur mit etwa einem zehntel mit dem vom Targacept bewertet sind. Da fühl ich mich auch viel wohler.

Grüße
Erbse

[KillingJoke]

Antwort auf Beitrag Nr.: 38.139.166 von Erbse1 am 08.10.09 13:13:10

Kapitalerhöhung!
Das TRGT Management selbst sieht wohl auch die Gelegenheit, zu diesem (hohen) Marktpreis mal den aktuellen Cashbestand zu verdoppeln (+46,2 Mio USD).

"Targacept, Inc. (NASDAQ: TRGT) announced today that the recently announced underwritten public offering of 2,200,000 shares of its common stock has been priced at a price to the public of $21.00 per share."

Bin mal gespannt ob die Aktionäre das wirklich mitmachen...

[KillingJoke]

Antwort auf Beitrag Nr.: 38.139.166 von Erbse1 am 08.10.09 13:13:10

Erbse1 schrieb:
"Zum Shorten wäre ich im Augenblick aber zu feige."

Am 15.10. werden die konkreten Ergebnisse der TC-5214 Phase II vorgestellt. Da könnte der geneigte Investor erstmal denken: "Prima Ergebnisse, es geht weiter up!"

Allerding gebe ich zu bedenken, dass das die Ergebnisspräsentation zu jener Vorankündigung ist, die die Aktie bereits 630% (in Worten sechhundertdreissig Prozent) hat steigen lassen. Eine ziemlich lange Einbahnstrasse.
Gute Ergenisse aber ein dann fallender Kurs könnte ein entsprechend tödlicher Witz sein.

Ich habe Zweifel ob die 21 USD halten (Erhöhung zu 21 USD geplant).
Die Kaptialerhöhungs-News gestern brachte den Kurs (20,56 USD Schluss) schon mal fast 2 USD in die von mir angenommene Richtung.

[Erbse1]

Antwort auf Beitrag Nr.: 38.145.026 von KillingJoke am 09.10.09 08:26:30

Hallo KillingJoke,
wenn ich immer Recht an der Börse hätte, brauchte ich nicht mehr zu arbeiten. Da sind Unwägbarkeiten, die kann man nicht voraussehen, wenn man kein Insider ist. Ich habe nichts dagegen, wenn Leute Aktien shorten, wenn sie die Papiere für überbewertet halten. Ich halte nicht viel von dieser Strategie. Ich suche lieber nach unterbewerteten Aktien und mache dann ausführliche Recherchen. Diese verfolge ich dann auch über mehrere Jahre und steige bei passender Gelegenheit wieder ein. Manchmal führt diese Strategie zum Erfolg. Manchmal setzt man auch aufs falsche Pferd. Es gibt keinen an der Börse, bei dem alle Entscheidungen richtig sind. Ich wünsche dir viel Glück und Können bei deinen Entscheidungen.
Grüße
Erbse

[KillingJoke]

Antwort auf Beitrag Nr.: 38.148.200 von Erbse1 am 09.10.09 15:07:14

Hallo Erbse,


ich denke wir sind alle hier in Biochtechs (long) unterwegs, weil wir auf den grossen Durchbruch und die Kursvervielfachung hoffen.
Ethisch gesehen gibts bei erfolgreichen Medikamenten sogar noch das gute Gefühl, an für Menschen positiven Dingen beteiligt zu sein.

Ich shorte selten, denn die Gewinne sind nun mal begrenzt (bei theortetisch unbegrenztem Verlustrisiko).
Ich hab da auch lieber die Entscheidung für ein Invest und dann den Tenbagger (wie mit VNDA).

Trotzdem verhilft gelegentliches Short Selling zu einer gewissen Ausgewogenheit. Verluste bei Longpositionen lassen sich vermeiden, wenn die "rosarote Brille" ein wenig wegtrainiert wird.

Ich wollte hier auch nicht so erscheinen, als hätte ich die Weisheit gepachtet.
Ich hab keine Ahnung - das ist sicher

Ein schönes Wochenende wünscht
KJ

[Erbse1]

Hallo KillingJoke, das ist das Gefährliche wenn man shortet. Heute werden noch mal die Ergebnisse präsentiert und der Kurs springt nach einigen Empfehlungen auf 24 $. So gehts auch manchmal.

Needham & Co Upgrades Targacept Inc. (TRGT) to Buy

Targacept (TRGT) Higher After Positive TC-5214 Trial For Major Depressive Disorder
Needham & Co Upgrades Targacept Inc. (TRGT) to Buy

Targacept Presents Data from Highly Successful Phase 2b Trial of TC-5214 as Augmentation Treatment for Major Depressive Disorder

October 16, 2009 8:18 AM EDT

Needham & Co upgrades Targacept Inc. (Nasdaq: TRGT) form Hold to Buy with a $26 price target, after the company presented impressive results from the Phase 2b TC5214 trial in depression yesterday.

The firm notes: "A clinically meaningful and statistically significant 7.54 point difference on the MADRS scale was reported (17.26 improvement for TC5214 vs. 9.72 for placebo). We note that the improvement is roughly double the effect observed with aripiprazole. Safety profile appears strong as well and we note that only one patient discontinued due to AE in the TC5214 arm."

Needham said the data position TC5214 favorably as an adjunctive agent for depression and it has blockbuster potential.

[Erbse1]

Targacept arbeitet auch an dem Themengebiet Parkinson und Nikotinrezeptoren. Dieses Anwendungsgebiet ist an GlaxoSmithKline auslizensiert. Jede Menge Hintergrundinformation zu diesem Thema.

European Neurological Society (ENS)

M. Parkinson: ein Synonym für viele Entitäten

Umfangreiche Evidenz weist heute darauf hin, dass die motorischen Symptome bei M. Parkinson nur die Spitze des Eisbergs sind; die Erkrankung scheint ihren Ausgang zumindest bei einigen Patienten nicht in der Substantia nigra zu nehmen und ist durch eine Fülle nicht motorischer Vorläufersymptome gekennzeichnet. Ein heterogenes Bild ergibt auch die Ursachenforschung.

Aszendierende Pathologie

Eine Parkinsondiagnose wird klassischerweise nach dem Auftreten der motorischen Symptome gestellt, bei der Befragung geben die Patienten allerdings sehr häufig auch andere Beschwerden wie Hyposmie, leichte Ermüdbarkeit, Konzentrationsprobleme, Depression, chronische Obstipation, Blasendysfunktion, Schmerzen oder REM-Schlaf-Verhaltensstörung an, die zum Teil viele Jahre zurückreichen. Hinweise auf das Vorhandensein eines präklinischen Parkinson-Stadiums liefert auch die Bildgebung. „Mittels 18-F-Dopa-PET und DAT-SPECT konnte eine präsymptomatische nigrostriatale Dysfunktion nachgewiesen werden“, berichtete Prof. Dr. Eduardo Tolosa, Universität Barcelona. Motorische Symptome manifestieren sich erst, wenn ein Verlust nigraler Zellen von 50% und ein striataler Dopaminverlust von 80% stattgefunden haben. „DAT-SPECT-Untersuchungen weisen auf eine prämotorische Phase im Umfang von fünf bis 13 Jahren hin.“

In dieser Periode ist nicht nur das dopaminerge System betroffen, sondern auch andere Systeme, die durch nicht motorische Symptome auffällig werden (Tab.). „Die prämotorische Phase kann uns helfen, den tatsächlichen Beginn der Krankheit zu definieren“, betonte Tolosa. Lewy-Körperchen finden sich auch bei Personen ohne Demenz und M. Parkinson. „Man nimmt an, dass sie das präsymptomatische Stadium bei Patienten repräsentieren, die vor der Entwicklung motorischer Symptome sterben.“

Gemäß der Hypothese von Braak startet die Neurodegeneration bei M. Parkinson im dorsalen motorischen Nukleus des N. vagus in der Medulla oblongata und steigt in der Folge bis zum Kortex auf. Braak definierte sechs Stadien, wobei im Rahmen der ersten drei die Substantia nigra gar nicht involviert ist. „Das ist die prämotorische Phase“, so Tolosa. Theoretisch ist es sogar möglich, dass die Pathologie ihren Ausgang vom peripheren autonomen Nervensystem nimmt.

Risikofaktoren für die Krankheitsmanifestation

Olfaktorische Strukturen dürften sehr früh am Krankheitsprozess beteiligt sein. Die idiopathische Hyposmie ist ein präklinisches Zeichen und kann sich vier Jahre oder länger vor dem Eintritt motorischer Symptome manifestieren. Dasselbe gilt für die REM-Schlaf-Verhaltensstörung (RBD); einer prospektiven Studie zufolge wird ein M. Parkinson bei vielen Patienten mit RBD nach einem durchschnittlichen Zeitintervall von zwölf Jahren evident. „RBD ist eine im kaudalen Hirnstamm lokalisierte Störung“, so Tolosa. „Das stimmt mit der Theorie von Braak überein.“

Auch bei der Obstipation handelt es sich um einen klaren Risikofaktor für M. Parkinson. Die Honolulu-Asia Aging Study ermittelte eine direkte Assoziation zwischen Stuhlfrequenz und Anzahl der Lewy-Körperchen. Ebenso konnte eine sympathische Denervation des Herzens bereits vor dem Auftreten motorischer Symptome belegt werden. „Klinische Hinweise auf eine kommende Parkinson-erkrankung finden sich vier bis 20 Jahre vorher, pathologische Hinweise sieben bis acht Jahre“, fasste Tolosa zusammen. Der vom Neuroimaging markierte Zeitrahmen liegt bei sieben bis 13 Jahren. „Bei Vorliegen bestimmter Mutationen kann die Krankheit theoretisch schon bei der Geburt beginnen.“ Der Experte riet allerdings zur Vorsicht, da das Vorhandensein nicht motorischer Symptome in der prämotorischen Phase kein konsistenter Befund ist. „Der M. Parkinson ist eine heterogene Erkrankung.“ Verschiedene Ursachen könnten mit unterschiedlichen prämotorischen Verläufen einhergehen. „Insgesamt lässt sich jedoch zumindest bei einigen Patienten sagen, dass die Krankheit außerhalb der Substantia nigra beginnt und viele Jahre vor der Manifestation motorischer Symptome ihren Anfang nehmen kann.“ Die Implikationen für krankheitsmodifizierende Therapien liegen auf der Hand: „Man könnte schon Jahre vor dem Beginn motorischer Symptome eine Behandlung initiieren.“

Ätiologie: Umwelt vs. Gene

Einige Fakten sprechen dafür, dass Umweltfaktoren für die Manifestation eines M. Parkinson ausschlaggebend sind:

• Existenz des postenzephalitischen Parkinsonismus

• Geografische Cluster (Guam, Guadelupe)
• Toxischer Parkinsonismus (MPTP, Rotenon, proteasomale Inhibitoren)

• Assoziation mit Pestizidexposition

• Inverse Assoziation mit Zigarettenkonsum

Zur Korrelation des M. Parkinson mit Pestizidexposition existieren viele Studien, allerdings besteht keine ausreichende Evidenz für eine kausale Beziehung. „Auch konnte keine spezifische Substanz identifiziert werden“, erklärte Prof. DDr. Vincenzo Bonifati, Abteilung für klinische Genetik, Erasmus Medical Centre, Rotterdam. „Hier ist die endgültige Antwort noch ausständig.“

Robuste Daten aus prospektiven und retrospektiven Studien belegen dagegen die starke inverse Assoziation zwischen M. Parkinson und Zigarettenkonsum. „Rauchen bedingt eine Risikoreduktion um ca. 50%“, so Bonifati. „Dieser Effekt geht nachgewiesenermaßen nicht auf die Zensur infolge der Krebsmortalität zurück.“ Wie die Cancer Prevention Study II zeigt, variiert die Risikoreduktion in Abhängigkeit von der Dauer und Intensität des Zigarettenkonsums und dem Zeitintervall ab Beendigung des Rauchens (Abb.).

Mögliche Ursachen sind ein potenziell protektiver Effekt von Tabak sowie die prämorbide (hypodopaminerge) Parkinson-Persönlichkeit, die zur Abstinenz neigt. Im Gehirn von Rauchern ist die Monoaminoxidase A und B deutlich downreguliert, woraus eine Reduktion des oxidativen Stresses und somit eine Neuroprotektion resultiert.

Populationsbezogene genetische Architektur

In der Erforschung der genetischen Grundlagen des M. Parkinson wurden in den letzten Jahren große Fortschritte gemacht. Die Entdeckung der Assoziation zwischen α-Synuklein und M. Parkinson war ein wichtiger Meilenstein, die Identifikation des PARK8-Locus ein weiterer. „Nur für vier bis fünf Mutationen existiert ein definitiver Beweis, dass sie die Krankheit hervorrufen können“, erläuterte Bonifati.

Am häufigsten ist die LRRK2-Gly2019Ser-Mutation, die als erste gemeinsame genetische Determinante des typischen M. Parkinson mit spätem Beginn identifiziert wurde; sie beeinflusst die Ätiopathogenese der familiären und der sporadischen Krankheitsform. „Der Ansatz am LRRK2-Pathway könnte neue therapeutische Möglichkeiten eröffnen“, so Bonifati. „Auch erleichtern asymptomatische Carrier die Erforschung der Bedeutung von Biomarkern, genetischen Faktoren und Umwelteinflüssen.“ Wie Bonifati hervorhob, variiert die genetische Architektur der Erkrankung in verschiedenen Populationen. So ist die LRRK2-Gly2019Ser-Mutation in einigen Volksgruppen in Nordafrika und dem Nahen Osten besonders prävalent. „Ein Drittel der Parkinsonpatienten in der Gruppe der Ashkenazi-Juden weist entweder die LRRK2-Gly2019Ser- oder die GBA-Mutation auf.“

Entität mit vielen Facetten

Eine weitere wichtige Erkenntnis besteht darin, dass der mit den Mutationen assoziierte nigrale Neuronenverlust nicht an das Auftreten von Lewy-Körperchen gebunden ist. „Wir müssen überdenken, ob Lewy-Körperchen eine Voraussetzung für die Diagnose sind“, so Bonifati. „Aus genetischer Perspektive ist die Antwort nein.“ Schließlich entscheidet der Aspekt der Penetranz über den Phänotyp. Ein Teil der Personen mit einer Mutation weist einen subklinischen Phänotyp auf, z.B. inzidentelle Lewy-Körperchen. „Von diesen Patienten entwickelt wiederum nur ein Teil einen M. Parkinson.“ Die klinische Penetranz der LRRK2-Gly2019Ser-Mutation liegt einigen Studien zufolge zwischen 24% und 74%. In der Synopsis erklären Mutationen allerdings nur einen kleinen Teil der Erkrankungen. „Es gilt noch viele genetische Determinanten und Umweltfaktoren zu identifizieren.“ Aus ätiologischer und pathogenetischer Sicht handelt es sich beim M. Parkinson nicht um eine Erkrankung, sondern um viele verschiedene. „Wir müssen das ganze Bild betrachten.“





Autor:
Dr. Judith Moser

Quelle des Artikels M. Parkinson: ein Synonym für viele Entitäten:
19. Jahrestagung der European Neurological Society (ENS), Symposium „Parkinson’s disease: advances in diagnosis and treatment“, 24. Juni 2009, Mailand

Quelle:http://www.universimed.com/frame.php?frame=http%3A//www.univ…

[KillingJoke]

Antwort auf Beitrag Nr.: 38.194.901 von Erbse1 am 16.10.09 17:01:24

Hallo Erbse,

ich muss anerkennen, das die Ergebnisse des TC-5214 Phase 2b Trial ausgezeichnet waren! Der Kurs ist von 20 auf 24,50 USD gesprungen, mit dem neuen Jahresjoch hatte ich nicht gerechnet.
Mittlerweile ist der Kurs auf 22,55 USD runtergekommen und wir stehen exakt da, wo wir am 08.10. auch schon mal waren.

Ich muss lobend anerkennen, dass das Timing für die Kapitalerhöhung sehr gut war. Ich hatte meine Zweifel, ob das alles nach dem exorbitanten Kursverlauf so klappen kann. Jetzt denke ich, sie dürfte durch sein.

KJ

[KillingJoke]

Antwort auf Beitrag Nr.: 38.212.884 von KillingJoke am 20.10.09 13:11:41

Auch interessant:
Großaktionär BFV hat oberhalb des Kurses für die Kapitalerhöhung (bei 23,60 USD) für 15 Millionen USD Targacept Aktien verkauft. Das erklärt den recht raschen Rückfall des Kurses in Richtung 21 USD.

[KillingJoke]

Antwort auf Beitrag Nr.: 38.230.727 von KillingJoke am 22.10.09 13:11:07

Wenn ich long wäre, würde mich das aber nicht ängstigen, denn vielleicht stockt BFV den Anteil im Zuge der Kapitalerhöhung einfach wieder auf. Das wären dann schnell verdiente 1,66 Mio USD.

[Erbse1]

Antwort auf Beitrag Nr.: 38.230.727 von KillingJoke am 22.10.09 13:11:07

Ja, das machen die gerne. Wenn die für 21.00 $ neue Aktien bekommen, dann lohnt sich das doch. Dann haben die doch mal eben gut 10% gemacht.
Die Deutsche Bank hat das auch mal gemacht bei Kursen um die 10 $. Wenn die von Kapitalmaßnahmen was hören, wird halt die Kacke verkauft. Du als Kleinanleger bist immer angeschissen, da du immer als letzter davon erfährt. Dann kaufst du noch die teuren Aktien ab. Die verkaufen ihre Pakete und decken sich dann billiger wieder ein.
Ich geh jetzt auch nicht mehr rein. Habe leider den Einstieg verpasst. Langfristig hat Targacept sicher noch Potenzial. Irgendwann streube ich mich dann auch dagegen.
Grüße
Erbse

[KillingJoke]

Antwort auf Beitrag Nr.: 38.212.884 von KillingJoke am 20.10.09 13:11:41

Habe meine Short-Position bei 20 USD glattgestellt.

[KillingJoke]

Antwort auf Beitrag Nr.: 38.212.884 von KillingJoke am 20.10.09 13:11:41

Hallo Erbse,


die Ergebnisse des TC-5214 Phase 2b Trial waren wirklich gut.
Wie gut zeigt sich in der folgenden Meldung.
AstraZeneca wurde als Partner gefunden:
"AstraZeneca and Targacept Form Global Collaboration and License Agreement for Late-stage Investigational Product TC-5214 for the Treatment of Major Depressive Disorder"

Auszug:
"December 03, 2009
(...)Under the agreement, AstraZeneca will make an upfront payment to Targacept of $200 million upon effectiveness and up to an additional $540 million if specified development, regulatory and first commercial sale milestones are achieved. Targacept will also be eligible to receive up to $500 million if specified sales related milestones are achieved as well as significant stepped double-digit royalties on net sales worldwide. (...)"

Quelle: http://www.targacept.com/wt/page/pr_1259822166

[KillingJoke]

Antwort auf Beitrag Nr.: 38.501.711 von KillingJoke am 03.12.09 13:06:26

-12% auf 20,65 USD:
Buyout stand wohl auf der Weihnachts-Wunschliste
und nicht der Deal.

[Erbse1]

Targacept Receives $200 Million Upfront Payment from AstraZeneca

WINSTON-SALEM, N.C.--(BUSINESS WIRE)--Targacept, Inc. (Nasdaq: TRGT - News), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics™, today announced that its collaboration and license agreement with AstraZeneca for the global development and commercialization of TC-5214 for major depressive disorder (MDD) has become effective as a result of early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act. Effectiveness of the agreement triggered an upfront payment of $200 million from AstraZeneca to Targacept.

AstraZeneca and Targacept are preparing for the planned mid 2010 initiation of Phase 3 clinical development of TC-5214 as an adjunct to antidepressant therapy in adults with MDD who do not respond adequately to first-line antidepressant treatment, with the goal of filing a new drug application with the U.S. Food and Drug Administration in 2012. The companies also plan to conduct a Phase 2 study exploring TC-5214 as a monotherapy for MDD.

Details of the Collaboration and License Agreement

As previously announced, Targacept is eligible under the agreement to receive an additional $540 million if specified development, regulatory and first commercial sale milestones are achieved, up to an additional $500 million if specified sales related milestones are achieved and significant stepped double-digit royalties on net sales worldwide. Under the terms of an existing license agreement, Targacept is required to pay a percentage of the upfront payment and each of the milestone payments that may be received from AstraZeneca, as well as royalties, to the University of South Florida Research Foundation. Targacept has retained an option for a co-promotion of TC-5214 to a limited target physician audience in the United States.

Under the terms of the agreement, AstraZeneca is responsible for 80% of the costs of the initial global development program for TC-5214 and Targacept is responsible for the remaining 20%, except that AstraZeneca is responsible for 100% of development costs that are required only to obtain or maintain regulatory approval in countries outside the United States and the European Union. AstraZeneca is also responsible for executing and funding the costs of global commercialization of TC-5214 and has agreed to assume Targacept's manufacturing and supply agreements with third parties in relation to TC-5214. The agreement also provides for a specified period for the parties to negotiate a potential multi-year research program that would be conducted by Targacept to identify and develop additional NNR Therapeutics for MDD and possibly other indications.

Existing Collaboration for Cognitive Disorders

In addition to the TC-5214 collaboration, Targacept and AstraZeneca have a global collaboration focused on cognitive disorders entered into in 2005. Three product candidates in the collaboration are currently in clinical development; including AZD3480 for attention deficit/hyperactivity disorder (ADHD), AZD1446 for Alzheimer’s disease, and TC-5619 for cognitive dysfunction in schizophrenia.