Summary of the pipeline
Thanks for the info. It's nice to see other sites with MS clinical trial lists. On the 2 you mention that aren't in our list, if you check out some posts on page 11 of the thread, these trials appear to have failed, so I think we are just more up to date than the other list. I will change the name of 2007 to 2077.
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CureOrBust
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what about SB-683699? I couldnt find it in the list.
http://www.clinicaltrials.gov/ct/show/N ... 17?order=3
Is it there, or do you wait until the trial actually starts in Jan?
http://www.clinicaltrials.gov/ct/show/N ... 17?order=3
Is it there, or do you wait until the trial actually starts in Jan?
A new approach in pre-clinical.
Dipeptidyl peptidase IV (DP IV, CD26) and aminopeptidase N (APN, CD13) as regulators of T cell function and targets of immunotherapy in CNS inflammation.
Int Immunopharmacol. 2006 Dec 20;6(13-14):1935-42.
Reinhold D, Biton A, Pieper S, Lendeckel U, Faust J, Neubert K, Bank U, Tager M, Ansorge S, Brocke S.
Institute of Immunology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
The ectoenzymes dipeptidyl peptidase IV (DP IV, CD26) and aminopeptidase N (APN, CD13) have been implicated in the regulation of T cell activation and function. Both DP IV and APN serve as targets of efficient enzymatic inhibitors which induce autocrine production of TGF-beta1 and subsequent suppression of T cell proliferation and cytokine release.
Here, we tested the hypothesis that the simultaneous inhibition of DP IV and APN enzymatic activity on leukocytes potentiates the anti-inflammatory effect of single DP IV or APN inhibitors. Our data show that the combined application of DP IV and APN inhibitors increased suppression of DNA synthesis in human peripheral blood mononuclear cells and isolated T cells in vitro when compared to the use of a single ectopeptidase inhibitor. Moreover, the combined action of DP IV and APN inhibitors markedly increased TGF-beta1 production associated with the observed immunosuppressive effects.
In vivo, targeting DP IV and APN provided a potent therapeutic approach for the treatment of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Taken together, our study suggests that combined DP IV and APN inhibition on pathogenic T cells represents a novel and efficient therapy for autoimmune disease of the central nervous system by a mechanism that involves an active TGF-beta1-mediated anti-inflammatory effect at the site of pathology.
Pubmed reference
Dipeptidyl peptidase IV (DP IV, CD26) and aminopeptidase N (APN, CD13) as regulators of T cell function and targets of immunotherapy in CNS inflammation.
Int Immunopharmacol. 2006 Dec 20;6(13-14):1935-42.
Reinhold D, Biton A, Pieper S, Lendeckel U, Faust J, Neubert K, Bank U, Tager M, Ansorge S, Brocke S.
Institute of Immunology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
The ectoenzymes dipeptidyl peptidase IV (DP IV, CD26) and aminopeptidase N (APN, CD13) have been implicated in the regulation of T cell activation and function. Both DP IV and APN serve as targets of efficient enzymatic inhibitors which induce autocrine production of TGF-beta1 and subsequent suppression of T cell proliferation and cytokine release.
Here, we tested the hypothesis that the simultaneous inhibition of DP IV and APN enzymatic activity on leukocytes potentiates the anti-inflammatory effect of single DP IV or APN inhibitors. Our data show that the combined application of DP IV and APN inhibitors increased suppression of DNA synthesis in human peripheral blood mononuclear cells and isolated T cells in vitro when compared to the use of a single ectopeptidase inhibitor. Moreover, the combined action of DP IV and APN inhibitors markedly increased TGF-beta1 production associated with the observed immunosuppressive effects.
In vivo, targeting DP IV and APN provided a potent therapeutic approach for the treatment of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Taken together, our study suggests that combined DP IV and APN inhibition on pathogenic T cells represents a novel and efficient therapy for autoimmune disease of the central nervous system by a mechanism that involves an active TGF-beta1-mediated anti-inflammatory effect at the site of pathology.
Pubmed reference
I don't like the looks of this info, AstraZeneca getting out of MS research -- they have 2 substances in phase I for MS and at least one pre-clinical. What will become of these trials? Stay tuned...
The chief executive of AstraZeneca has said that the company intends to reduce the number of diseases for which it develops new drugs and concentrate on acquisitions and licensing deals in its core areas.
David Brennan told the Financial Times of the firm's intention to withdraw from hypertension, functional gastro-intestinal disorders, inflammatory bowel diseases, Parkinson's disease, multiple sclerosis, addiction, insomnia and stroke. From now on, it will concentrate on diabetes and obesity, infection, inhalation projects, analgesia and oncology.
"Our primary focus is in areas where we have existing therapies... (and) are most likely to get a hit. Right now we are much more focused on areas where we are strong, rather than in diversity," Mr Brennan said.
His comments seem to rule out any future bid for Shire, as had been rumoured, since it specialises in attention deficit disorder, gastro-intestinal and renal diseases and human genetic therapies.
http://www.pharmatimes.com/WorldNews/Ar ... spx?src=WN
The chief executive of AstraZeneca has said that the company intends to reduce the number of diseases for which it develops new drugs and concentrate on acquisitions and licensing deals in its core areas.
David Brennan told the Financial Times of the firm's intention to withdraw from hypertension, functional gastro-intestinal disorders, inflammatory bowel diseases, Parkinson's disease, multiple sclerosis, addiction, insomnia and stroke. From now on, it will concentrate on diabetes and obesity, infection, inhalation projects, analgesia and oncology.
"Our primary focus is in areas where we have existing therapies... (and) are most likely to get a hit. Right now we are much more focused on areas where we are strong, rather than in diversity," Mr Brennan said.
His comments seem to rule out any future bid for Shire, as had been rumoured, since it specialises in attention deficit disorder, gastro-intestinal and renal diseases and human genetic therapies.
http://www.pharmatimes.com/WorldNews/Ar ... spx?src=WN
Thought I'd check on the status of some phase I drugs. Got off to a bad start, I found that one of the Astrazeneca drugs in phase I failed, although they are getting out of MS treatments, so that might not be a big deal. Also, I could not find any specific references to which drugs in Allon's pipeline are going to be trialled for MS, so I removed AL108 from the pipeline as it is only being tested for Alzheimers right now.
Looking through the phase I list to update it and I found that "DADMe-Immunicillin-H (Albert Einstein College of Medicine)" has been licensed to Biocryst and Roche, who have both taken the trouble to give it their own creative names. For Biocryst, they went with BCX-4808, whereas Roche took a subtler approach and called it R3421. Anyhow, I'll keep it in phase I, even though the focus appears to be on transplant patients and lupus initially.
BCX-4208 (PNP Inhibitor)
BCX-4208, a second generation transition-state analog inhibitor of the enzyme purine nucleoside phosphorylase (PNP), may have the potential to offer greater efficacy and activity in the treatment of autoimmune disease and transplant rejection than currently available therapies. Although BCX-4208 and Fodosine™ are both investigational PNP inhibitors, BCX-4208 differs from Fodosine™ in significant ways. For example, BCX-4208 is more potent, and has the ability to suppress PNP for longer periods of time. Thus, BCX-4208 has potential advantages over Fodosine™ for the treatment of diseases requiring long-term, chronic administration of a PNP inhibitor.
In August 2005, BioCryst initiated a phase Ib trial in healthy volunteers to evaluate the safety, tolerability and pharmacokinetics of multiple oral doses of BCX-4208 with the goal of beginning a Phase II trial in psoriasis patients.
In November 2005, BioCryst entered into an exclusive worldwide licensing agreement with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. (“Roche”) to develop and commercialize BCX-4208 for the prevention of acute rejection in transplantation and for the treatment of autoimmune diseases. This collaboration provided substantial strategic and economic benefit to BioCryst while also providing all the essential elements for the rapid, comprehensive and competitive development of BCX-4208. The two companies have established a joint committee to set the clinical development strategy and the future development program for BCX-4208.
http://www.biocryst.com/bcx_4208.htm
BCX-4208 (PNP Inhibitor)
BCX-4208, a second generation transition-state analog inhibitor of the enzyme purine nucleoside phosphorylase (PNP), may have the potential to offer greater efficacy and activity in the treatment of autoimmune disease and transplant rejection than currently available therapies. Although BCX-4208 and Fodosine™ are both investigational PNP inhibitors, BCX-4208 differs from Fodosine™ in significant ways. For example, BCX-4208 is more potent, and has the ability to suppress PNP for longer periods of time. Thus, BCX-4208 has potential advantages over Fodosine™ for the treatment of diseases requiring long-term, chronic administration of a PNP inhibitor.
In August 2005, BioCryst initiated a phase Ib trial in healthy volunteers to evaluate the safety, tolerability and pharmacokinetics of multiple oral doses of BCX-4208 with the goal of beginning a Phase II trial in psoriasis patients.
In November 2005, BioCryst entered into an exclusive worldwide licensing agreement with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. (“Roche”) to develop and commercialize BCX-4208 for the prevention of acute rejection in transplantation and for the treatment of autoimmune diseases. This collaboration provided substantial strategic and economic benefit to BioCryst while also providing all the essential elements for the rapid, comprehensive and competitive development of BCX-4208. The two companies have established a joint committee to set the clinical development strategy and the future development program for BCX-4208.
http://www.biocryst.com/bcx_4208.htm
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CureOrBust
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My favorite thing to do with this list: move something along the pipeline. Just saw that Incyte is initiating a phase I trial of INCB8696, which was on the list in pre-clinical.
In his presentation at the JPMorgan Conference, Dr. Friedman will also describe progress in several of the company's drug development programs, including:
-- The filing of an Investigational New Drug Application (IND) for its lead CCR2 antagonist, INCB8696, which Incyte intends to develop first as an oral treatment for multiple sclerosis. Incyte may also pursue a second indication, lupus nephritis, and potentially other autoimmune nephritides. The Phase I trial is expected to initiate in the first quarter of this year.
http://www.medadnews.com/News/Index.cfm ... eid=404311
In his presentation at the JPMorgan Conference, Dr. Friedman will also describe progress in several of the company's drug development programs, including:
-- The filing of an Investigational New Drug Application (IND) for its lead CCR2 antagonist, INCB8696, which Incyte intends to develop first as an oral treatment for multiple sclerosis. Incyte may also pursue a second indication, lupus nephritis, and potentially other autoimmune nephritides. The Phase I trial is expected to initiate in the first quarter of this year.
http://www.medadnews.com/News/Index.cfm ... eid=404311
Continuing my review of the phase I's, unfortunately, Genz-29155 appears to have failed a long time ago (2004), oops.
In multiple sclerosis, Genzyme has shifted its focus from Genz-29155 to an alternative internally developed compound due to safety issues observed in the phase 1 trial, which has been suspended.
http://www.biospace.com/news_story.aspx ... 820&full=1
In multiple sclerosis, Genzyme has shifted its focus from Genz-29155 to an alternative internally developed compound due to safety issues observed in the phase 1 trial, which has been suspended.
http://www.biospace.com/news_story.aspx ... 820&full=1
I found another one (NI-0401) in phase I trials for "autoimmune diseases", including MS, so I added it to the list based on this:
http://www.novimmune.com/platforms/humabs/humab9.php
http://www.novimmune.com/platforms/humabs/humab9.php