
Aviara is leading the development of small molecule integrin inhibitors that modulate the activity of stem cells and inflammatory cells.
Aviara’s lead clinical candidate, AVA4746, is being developed for the mobilization of hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with leukemia or lymphoma. In addition to AVA4746, Aviara is also developing a portfolio of small-molecule antagonists against a variety of integrin targets involved in the modulation of cell therapies and inflammatory disease such as minimal residual disease in cancer, cardiac stem cell transplant, dry eye disease and inflammatory bowel disease.
Aviara has a collaboration with the Texas Heart Institute (THI) to explore the roles of integrins and other adhesion molecules in the development and trafficking of stem cells. Aviara and THI have entered into a joint discovery, development and cross-license agreement that provides access to THI research for the purpose of further development and commercialization.
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Management |
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George W. Holland, PhD, Cofounder, President and CEO
Prior to co-founding Aviara, George served 9 years at Encysive Pharmaceuticals, Inc. (formerly Texas Biotechnology Corp.) where he was Vice President of Chemical Sciences. Previous to Encysive, Dr. Holland was for 26 years with Hoffmann-La Roche (Nutley) where he served both as senior therapeutic area management and leader of medicinal/synthetic chemistry groups working on a broad range of synthetic and therapeutic targets. At Encysive he was involved in all phases of the drug discovery and development effort that resulted in the regulatory approval and commercialization of the endothelin antagonist Thelin™ in North America, Europe and Australia. Dr. Holland has more than 36 publications and 50 patents. He earned a PhD in organic chemistry from the Iowa State University and conducted postdoctoral studies at Purdue University with Nobel Laureate Herbert C. Brown.
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Richard A.F. Dixon, PhD, Cofounder, and Chairman of BOD
Richard is a cofounder of Aviara and is Director of Molecular Cardiology Research, Texas Heart Institute, Houston, Texas. Formerly he was a Founder, Director, Senior Vice President and Chief Scientific Officer of Encysive Pharmaceuticals, Inc. Prior to that, he held various management positions, including head of the molecular biology department at Merck and Co. where his basic research efforts focused on the molecular biology and pharmacology of intracellular signaling and cell trafficking, leading to become the first group to clone and characterize a G-protein coupled receptor, the beta2 adrenergic receptor (resulting in 2012 Nobel Prize in Chemistry to Kobilka and Lefkowitz). He conducted postdoctoral research Johns Hopkins University School of Medicine with the Nobel Laureate Daniel Nathans. He and his research groups have produced 10 NCEs which have entered into human testing, one of which has led to the approved drug Thelin™. He has also been directly involved with 4 other NDA programs that have resulted in the approved drugs Argatroban™, Crixivan™, Singular™, and Zocor™. While at Encysive, Dr. Dixon was involved in an IPO, several public stock offerings, and PIPEs which raised more than $340M over the 18 year history of Encysive. He is currently Director of the Wafic Said Molecular Cardiology Research Laboratories at the Texas Heart Institute (THI) in Houston, Texas, where he is involved in discovery and development of small molecule, gene and cell therapies for heart, lung and vascular diseases. At THI, he directs a large medicinal chemistry group which is actively involved in the discovery of small molecule therapeutic and diagnostic agents for application in regenerative medicine.
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Patrick Ward, Cofounder and Director
Patrick is the former President and COO of Ocusoft, Inc., a specialty ophthalmic pharmaceutical distributor. At Ocusoft, he was responsible for management of the organization with over 120 employees and a $30 million operating budget. He was also responsible for product development, manufacturing and regulatory affairs for a variety of pharmaceutical, cosmetic and nutritional supplement products.
Prior to joining Ocusoft, he was Executive Director of Business development at Encysive Pharmaceuticals where he spent 13 years in business development, finance and marketing, with responsibility for strategic financial planning, new business deal activities, licensing transactions and alliance management. He was also involved in the development and commercialization of two approved drugs – Argatroban™ and Thelin™ – in the U.S. and Europe. Prior to joining Encysive, he was with Owen Healthcare (now Cardinal Health) where he served in multiple roles in hospital pharmacy management. He received a B.S. in Pharmacy from The University of Houston and an M.B.A. in Finance from the University of St. Thomas. |
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Board of Directors |
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Richard A.F. Dixon, PhD
Chairman |
George Holland, PhD
Director |
Patrick Ward
Director |
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Our research focuses on modulating the activity of integrins. Integrins are a large family of adhesion molecules that are found on the surfaces of nearly all cells, mediating a wide variety of physiological processes, including cell adhesion, migration, survival and differentiation. Integrins play a key role in the inflammatory and immune response to disease. Consequently, integrins are involved in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders.
We are also exploring new ways of modulating the effects of stem cells and the stem cell niche. A stem cell is a unique cell that can proliferate and differentiate into other cell types with specialized functions such as those of muscle, brain, blood or skin. In adults, they contribute to the repair of damaged tissue by regenerating those cell types necessary for proper organ function. The stem cell niche is the microenvironment located within the bone marrow where the stem cells reside. The niche supports the maintenance of stem cell identity and regulates the function of stem cells. |
AVA4746 – Hematopoietic Stem Cell Mobilization |
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Aviara’s lead clinical candidate, AVA4746, is being developed for use as a mobilization agent in cancer patients undergoing autologous hematopoietic stem cell (HSC) transplantation. Each year, an estimated 35,000 autologous stem cell transplants are performed worldwide. HSC are the stem cells that mature to form blood and immune cells such as erythrocytes, leukocytes, etc. They are produced in the bone marrow, where they egress into the circulation and are ultimately responsible for the constant renewal of blood – the production of billions of new blood cells each day. But because only a small amount of HSC circulate in the peripheral blood at any time, it is necessary to use mobilization agents to drive them to the peripheral circulation where they can be collected for transplantation.
Recent research has shown a strong role for integrin antagonists to be used in the role of HSC mobilization. Aviara has conducted multiple studies of AVA4746 in preclinical models of HSC mobilization, results of which demonstrate a clear opportunity for the use of AVA4746 in HSC mobilization. The development goal of the program is to increase the yield of HSC in the peripheral blood so that fewer collection procedures are needed to collect the required number of HSC needed for transplantation.
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Cell Mediated Drug Resistance and Minimal Residual Disease |
Another area of particular interest for integrin antagonists is in the area of cell mediated drug resistance (CAM-DR). CAM-DR is developed when some cancerous cells remain sequestered and viable in the bone marrow and not affected by chemotherapy. These cells have been shown to act as the source for a relapse of the cancer, referred to as Minimal Residual Disease (MRD). We believe the use of integrin antagonists may play a key role in overcoming chemotherapy resistance and disease relapse by inhibiting the bond between the cancerous cells and the bone marrow niche, making the cancerous cells more susceptible to chemotherapeutic agents.
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Inflammatory Bowel Disease |
Inflammatory Bowel Disease (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract. The α4β7 integrin is considered to be the adhesion molecule principally involved in inflammation of the intestinal lining. Recently, a human monoclonal antibody to the α4β7 integrin was approved by the Food and Drug Administration, providing further validation of targeting the α4β7 integrin clinically.
It is estimated that as many as 1.4 million persons in the United States suffer from IBD, and IBD is one of the five most prevalent gastrointestinal disease burdens in the United States. Aviara is developing an oral, small molecule inhibitor of the α4β7 integrin as an alternative to injectable biologic products currently used in IBD. The market for pharmaceuticals indicated for the treatment of IBD and symptoms is estimated to reach $7.70 billion by 2017.
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Dry Eye Syndrome |
Dry eye syndrome (DES) or keratoconjunctivitis sicca, is a common ocular surface disease affecting tens of millions of people worldwide. It is one of the leading reasons for patients seeking treatment of symptoms of ocular discomfort and visual disturbance, and commonly leads to problems with activities that require sustained visual attention such as reading and driving. One of the mechanisms underlying the symptoms of DES is chronic inflammation of the ocular surface caused by an integrin-mediated response. Recent studies using a topically applied integrin antagonist demonstrated a significant reversal in corneal epithelial damage, a key driver of the chronic symptoms associated with dry eye.
With the worldwide market opportunity for dry eye treatments being in excess of $1 billion, we believe a topically applied integrin antagonist would represent a significant improvement in currently used therapies. Aviara will be developing the topical form of AVA3486 for use in the treatment of DES with the help of a corporate partner specializing in diseases of the eye.
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November 10, 2020 - Aviara Pharmaceuticals, Inc receives grant to collaborate with the Texas Heart Institute
December 14, 2014 - Aviara to Present at the Biotech Showcase 2015 Annual Conference

For information, please contact:
Aviara Pharmaceuticals, Inc.
3331 Green Tree Park
Houston, TX 77007
info@aviarapharma.com
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