Type | Public |
---|---|
Industry | Biotechnology |
Founded | 2001 |
Founders | |
Headquarters | Charlottesville, Virginia, U.S. |
Key people | Robert Cobuzzi, Jr (President and CEO) Jane H. Hollingsworth (Chairman of the Board) Christopher D. Galloway (Chief medical officer) [1] |
Products | Trans sodium crocetinate. |
Website | diffusionpharma.com |
Diffusion Pharmaceuticals Inc (NASDAQ:DFFN) is a publicly traded biotechnology and drug development company based in Charlottesville, Virginia, U.S. [2] It was co-founded in 2001 by American life sciences entrepreneur David Kalergis and University of Virginia Chemical Engineering Professor John L. Gainer. [2] Gainer is the inventor of the company’s platform technology of oxygen diffusion-enhancing compounds and its lead drug, trans sodium crocetinate (TSC). [3] TSC acts to increase the rate at which oxygen moves through blood plasma by the process of diffusion, [4] a phenomenon that forms the basis for the company's name. On January 8, 2016, the formerly privately-held company merged with Restorgenex Cororation to become a publicly-traded NASDAQ-listed company with the trading symbol DFFN. [5] TSC and other oxygen diffusion-enhancing compounds, including bipolar trans carotenoid salts (the subclass to which TSC belongs), have been investigated by Diffusion Pharmaceuticals for treatment of conditions associated with reduced oxygen availability in tissues (hypoxia). [2] Most recently, Diffusion has begun the initiation of clinical trials in the U.S. and Eastern Europe for the use of trans sodium crocetinate in the treatment of COVID-19 patients suffering from respiratory distress-related oxygen deficiency and the risk of multiple organ failure. [6]
Gainer invented the concept of oxygen diffusion-enhancing compounds and its specific embodiment, TSC, while a Professor of Chemical Engineering at the University of Virginia. He secured the first patent on the molecule and its uses in 2000. Before TSC's invention, he and colleagues conducted research on the effects of oxygen diffusion-enhancing compounds in various animal disease models, including atherosclerosis, arthritis and cancer. At that time, crocetin, a naturally occurring carotenoid compound, was the focus of their research. With the invention of TSC, their research turned to the potential use of this synthetic oxygen diffusion-enhancing compound for the improved treatment of hemorrhagic shock (shock caused by the loss of a large volume of blood) on the battlefield. [3] [4] [7] This research, which was supported financially by the United States Office of Naval Research (ONR), was conducted in Gainer’s University of Virginia laboratory. Following the company's formation by Kalergis and Gainer in 2001, both ONR [8] and private funding [9] was obtained, enabling company researchers to set up their own laboratory and, along with collaborators, perform further preclinical studies into uses of TSC in the treatment of hemorrhagic shock and other hypoxic conditions, such as ischemic stroke, central nervous system (CNS) disorders, and cancer. [4] [10] [11] [12]
In 2007, TSC was advanced into clinical trials in humans. Clinical investigation first centered on the drug's safety and pharmacokinetic (PK) parameters in normal healthy volunteers. This was followed in 2009-2010 by a multi-center, randomized, placebo-controlled clinical trial examining TSC’s safety and efficacy in the re-oxygenation of tissues in patients affected by peripheral artery disease. [13] The company is currently investigating the use of trans sodium crocetinate in the treatment of COVID-19, acute stroke, and solid cancerous tumors. [14]
Between 2008 and 2017, Diffusion Pharmaceuticals expanded its intellectual property portfolio, having been awarded new patents (in the United States and internationally) that covered the synthesis and uses of bipolar trans carotenoid salts and related compounds in peripheral artery disease, cancer and other indications. [15] In 2011, TSC received an orphan drug designation from the United States Food and Drug Administration for the use of TSC as a radiosensitizer in the treatment of newly diagnosed GBM patients. In accordance with standard practice, the Orphan Drug designation for TSC confers benefits including enhanced patent protection and marketing rights, waiver of certain FDA filing fees and favorable tax treatment. [16] By mid-2017, the company had been issued 14 U.S. and 46 international patents. [15] [17]
In 2012, Diffusion Pharmaceuticals won the Virginia Healthcare Innovators award in the “Medical Product or Device ” category for its development of TSC. [18]
An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases.
Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic microenvironements in solid tumors are a result of available oxygen being consumed within 70 to 150 μm of tumour vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue. In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism. Furthermore, hypoxia is known to change cell behavior and is associated with extracellular matrix remodeling and increased migratory and metastatic behavior.
The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered to patients, with the aim to cure them, vaccinate them, or alleviate the symptoms. Pharmaceutical companies may deal in generic or brand medications and medical devices. They are subject to a variety of laws and regulations that govern the patenting, testing, safety, efficacy and marketing of drugs.
Clopidogrel, sold under the brand name Plavix among others, is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following the placement of a coronary artery stent. It is taken by mouth. Onset of effects is about two hours and lasts for five days.
Gilead Sciences, Inc., is an American biopharmaceutical company headquartered in Foster City, California, that focuses on researching and developing antiviral drugs used in the treatment of HIV, hepatitis B, hepatitis C, and influenza, including Harvoni and Sovaldi.
CX717 is an ampakine compound created by Christopher Marrs and Gary Rogers in 1996 at Cortex Pharmaceuticals. It affects the neurotransmitter glutamate, with trials showing the drug improves cognitive functioning and memory.
Sodium oxybate, sold under the brand name Xyrem among others, is a medication used to treat two symptoms of narcolepsy: sudden muscle weakness and excessive daytime sleepiness. It is used sometimes in France and Italy as an anesthetic given intravenously; it is also used in Italy to treat alcohol addiction and alcohol withdrawal syndrome.
Crocetin is a natural apocarotenoid dicarboxylic acid that is found in the crocus flower and Gardenia jasminoides (fruits). It forms brick red crystals with a melting point of 285°C.
Zomepirac is an orally effective nonsteroidal anti-inflammatory drug (NSAID) that has antipyretic actions. It was developed by McNeil Pharmaceutical, approved by the FDA in 1980, and sold as the sodium salt zomepirac sodium, under the brand name Zomax. Due to its clinical effectiveness, it was preferred by doctors in many situations and obtained a large share of the analgesics market; however, it was subsequently withdrawn in March 1983 due to its tendency to cause serious anaphylaxis in a small, but unpredictable, subset of the patient population.
A radiosensitizer is an agent that makes tumor cells more sensitive to radiation therapy. It is sometimes also known as a radiation sensitizer or radio-enhancer.
Genta Incorporated was a biopharmaceutical company started in La Jolla, California, which discovered and developed innovative drugs for the treatment of patients with cancer. Founded in 1989 by a highly skilled entrepreneur, the company focused on a novel technology known as antisense, which targets gene products that are associated with the onset and progression of serious diseases. At that time, only Ionis Pharmaceuticals, Inc. was conducting significant research with this technology. Antisense is a short span of oligonucleotides – modified DNA structures ranging from about 12-24 bases that selectively bind to specific RNA. The intent is to block expression of an aberrant protein that contributes to the disease of interest. Genta in-licensed three different antisense molecules that blocked Bcl-2, a fibroblast growth factor (FGF), and the gene c-myb, respectively.
Temozolomide (TMZ), sold under the brand name Temodar among others, is a medication used to treat some brain tumors such as glioblastoma multiforme or anaplastic astrocytoma. It is taken by mouth or via intravenous infusion.
Varespladib is an inhibitor of the IIa, V, and X isoforms of secretory phospholipase A2 (sPLA2). The molecule acts as an anti-inflammatory agent by disrupting the first step of the arachidonic acid pathway of inflammation. From 2006 to 2012, varespladib was under active investigation by Anthera Pharmaceuticals as a potential therapy for several inflammatory diseases, including acute coronary syndrome and acute chest syndrome. The trial was halted in March 2012 due to inadequate efficacy. The selective sPLA2 inhibitor varespladib was studied in the VISTA-16 randomized clinical trial and the results were published in 2014. The sPLA2 inhibition by varespladib in this setting seemed to be potentially harmful, and thus not a useful strategy for reducing adverse cardiovascular outcomes from acute coronary syndrome. Since 2016, scientific research has focused on the use of Varespladib as an inhibitor of snake venom toxins using various types of in vitro and in vivo models. Varespladib showed a significant inhibitory effect to snake venom PLA₂ which makes it a potential first-line drug candidate in snakebite envenomation therapy. In 2019, the U.S. Food and Drug Administration (FDA) granted varespladib orphan drug status for its potential to treat snakebite.
An oxygen diffusion-enhancing compound is any substance that increases the availability of oxygen in body tissues by influencing the molecular structure of water in blood plasma and thereby promoting the movement (diffusion) of oxygen through plasma. Oxygen diffusion-enhancing compounds have shown promise in the treatment of conditions associated with hypoxia and ischemia. Such conditions include hemorrhagic shock, myocardial infarction, and stroke.
Crofelemer is a botanical drug for the treatment of diarrhea associated with anti-HIV drugs such as nucleoside analog reverse transcriptase inhibitors and protease inhibitors. Other possible uses include diarrhea in children, acute infectious diarrhea, and diarrhea in patients with irritable bowel syndrome. It is a purified oligomeric proanthocyanidin from "dragon's blood", the sap of the South American tree Croton lechleri.
John L. Gainer is an American chemical engineer and co-founder and former chief scientific officer of Diffusion Pharmaceuticals, a biotechnology and pharmaceutical company based in Charlottesville, Virginia, U.S. Professor Gainer retired from his position as Chief Science Officer of Diffusion Pharmaceuticals in March, 2020.
David Kalergis is an American life sciences entrepreneur and the Co-founder, Chairman and Chief Executive Officer of Diffusion Pharmaceuticals Inc, a Charlottesville, Virginia, U.S.-based biotechnology and pharmaceutical company. He co-founded the company in 2001 with American chemical engineer John L. Gainer. Kalergis became Diffusion's CEO in 2004, a position in which he has drawn extensively on his career in law, business, and clinical trials implementation. Under Kalergis' leadership, Diffusion Pharmaceuticals has been cited for advancing improved cancer treatments and is currently conducting multicenter clinical trials of a novel therapeutic for brain cancers, including glioblastoma multiforme. Diffusion Pharmaceuticals is also currently conducting clinical trials for the treatment of oxygen deficiencies associated with COVID-19 and acute stroke.
Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein. During the COVID-19 pandemic, remdesivir was approved or authorized for emergency use to treat COVID‑19 in around 50 countries. Updated guidelines from the World Health Organization in November 2020 include a conditional recommendation against the use of remdesivir for the treatment of COVID-19.
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COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research, with 419 potential COVID-19 drugs in clinical trials, as of April 2021.