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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: Andrew H who wrote (21281)	5/21/1998 5:33:00 AM
From: Henry Niman	Respond to of 32384

So far not that much has come out on LGD1550. It activates all three RARs as does Vesanoid (tretinoin or all-trans retinoic acid) and 13-cis retinoic acid (isotretinoin). The oral formulation of 13 cis-retinoic acid is in several clinical trials, including the trial on brain cancer. Vesanoid has been approved for treating APL, but can produce a fatal reaction: pharminfo.com LGND didn't present much on LGD1550 efficacy. It does seem to be fairly well tolerated and LGND is planning Phase II trials using it in combination with more conventional chemotherapy to treat head & neck and cervical cancer, where promising pre-clinical data has been generated: ncbi.nlm.nih.gov ncbi.nlm.nih.gov

To: Andrew H who wrote (21281)	5/22/1998 4:24:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Good news for LGND's IL-4 antagonist program to treat asthma: Thursday May 21 6:03 PM EDT Asthma-triggering cell identified NEW YORK (Reuters) -- The cause of the chronic inflammation that underlies asthma has long been a mystery, but now researchers believe they have identified the type of immune cell that may be responsible for the lung disorder. According to a report in the May 22nd issue of Science, a subset of white blood cells, known as gamma delta T cells, appear to drive the reaction that results in two of the hallmarks of asthma: the infiltration of the lungs with inflammatory cells and the lung's hypersensitive response to allergens or toxins. Dr. Claudia Zuany-Amorim and colleagues at the Institut Pasteur in Paris, France, bred a special strain of mouse that lacked gamma delta T cells. Unlike normal mice, the T cell-deficient mice did not have a dramatic increase in inflammatory cells in the lungs and blood after exposure to an asthma-inducing protein. An analysis of lung fluid showed that the T cell-deficient mice also produced lower levels of certain growth factors, including interleukin 5 (IL-5), interleukin 4 (IL-4) and interferon, as well as less IgE, an antibody responsible for allergic reactions. However, injecting the T cell-deficient mice with IL-4 restored the asthma-like reaction, suggesting that the growth factor plays a key role in the immune reaction. Further research into the function of gamma delta T cells "...will represent an important step for understanding and modulating" the immune response that leads to asthma, the researchers concluded. SOURCE: Science 1998;280:1265-1267.

To: Andrew H who wrote (21281)	5/22/1998 4:34:00 AM
From: Henry Niman	Respond to of 32384

Here's the abstract: Requirement for T Cells in Allergic Airway Inflammation Claudia Zuany-Amorim, * Claude Ruffi‚, Solomon Hail‚, B. Boris Vargaftig, Pablo Pereira, Marina Pretolani The factors that contribute to allergic asthma are unclear but the resulting condition is considered a consequence of a type-2 T helper (TH2) cell response. In a model of pulmonary allergic inflammation, mice that lacked T cells had decreases in specific immunoglobulin E (IgE) and IgG1 and pulmonary interleukin-5 (IL-5) release as well as in eosinophil and T cell infiltration compared with wild-type mice. These responses were restored by administration of IL-4 to T cell-deficient mice during the primary immunization. Thus, T cells are essential for inducing IL-4-dependent IgE and IgG1 responses and for TH2-mediated airway inflammation to peptidic antigens. C. Zuany-Amorim, C. Ruffi‚, B. B. Vargaftig, M. Pretolani, Unit‚ de Pharmacologie Cellulaire, Unit‚ Associ‚e Institut Pasteur/INSERM U485, Paris, France. P. Pereira, Unit‚ d'Immunobiologie, CNRS URA 1961, Institut Pasteur, Paris, France. S. Hail‚, Unit‚ d'Histopathologie, Institut Pasteur, Paris, France. * Present address: Novartis Horsham Research Centre, Horsham, UK.

To: Andrew H who wrote (21281)	5/22/1998 4:39:00 AM
From: Henry Niman	Respond to of 32384

Here's the Science summary: Lung allergies and gamma delta T cells Allergic asthma is initiated with the inhalation of an allergen. In a mouse model system in which mice are allergic to the protein ovalbumin, the role of T cells was tested. By comparing mice genetically deficient in T cells to wild-type mice, Zuany-Amorim et al. (p. 1265) show that these cells supply the cytokine interleukin-4 (IL-4) during the sensitization process. IL-4 is the component critical for setting up a T helper type 2 (TH2) response in the lung, which becomes infiltrated by inflammatory cells that produce cytokines and secrete immunoglobulin E (IgE), one of the hallmarks of the response. The identity of the cells that provide the IL-4 to push any immune response in the direction of TH2 has been elusive; at least in this system, it appears that the T cell, which previously had few definitive responsibilities, is the culprit.

To: Andrew H who wrote (21281)	5/22/1998 6:48:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

This is from thestreet.com review on asthma treatments: A new class, and one that is likely to perform the best, attacks the most fundamental of the mediators, IL-4. IL-4 is the first mediator to be released, and it starts the chain of events that ultimately results in the symptoms of asthma. Inhibiting or circumventing IL-4 will be critical. From this perspective, I give a thumbs up to Glaxo Wellcome, Ligand (LGND:Nasdaq) and Immunex (IMNX:Nasdaq). Of these three, Immunex is the furthest along in the development process, and its data, to be presented at the American Association of Allergy, Asthma and Immunology conference this March, will be most interesting.

To: Andrew H who wrote (21281)	5/22/1998 7:16:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Here's more on Asthma: By Sarah Wyatt The Associated Press W A S H I N G T O N,ÿÿÿMay 21 - Hillary Rodham Clinton today called for better education and preventive measures against asthma, a disease that affects about 5 million children in the United States. ÿÿÿÿ While most children celebrate the freedom that comes with the dog days of summer, others lament the smog, ozone and other allergens in the air that can cause frightening asthma attacks. Cases of asthma among preschoolers rose 160 percent from 1980 to 1994, Health and Human Services Secretary Donna Shalala said. ÿÿÿÿ "We know asthma is the most common medical threat to America's children and the problem is getting worse. That is why we are trying to sound the alarm," Clinton said. ÿÿÿÿ Asthma is a chronic lung disease that triggers episodes of wheezing, breathlessness, tightness of the chest and coughing. People with asthma spend almost 100 million days of restricted activity each year, and children who suffer from asthma miss about twice as many school days as other children. ÿÿÿÿ Clinton announced efforts to educate parents and communities about how to handle and prevent asthma attacks. A new National Ozone Map gives ozone levels and forecasts daily and will be provided to local weather broadcasts and on the Internet by the Environmental Protection Agency. Pilot Program to Come The Clinton administration will also conduct a pilot program to identify and prevent environmental risks to children in 11 communities. Local health care providers, teachers, government officials and business owners will work together to reduce children's health risks. ÿÿÿÿ Sesame Street's Elmo and Luis joined Clinton for the announcements at Children's National Medical Center. Children's Television Workshop and the American Lung Association have created a multimedia packet called "Sesame Street A is for Asthma," a nationwide, bilingual childhood asthma awareness project. ÿÿÿÿ Luis sang "The Breathing Song" while the children and Clinton impersonated elephants to show the importance of breathing deeply. ÿÿÿÿ Luis noted that the cast of Sesame Street sent their best wishes, with the exception of the notorious Oscar the Grouch. Luis quoted him as saying: "Try to imagine how little I care." ÿÿÿÿ Apparently, Oscar is not an asthma sufferer.