SLC4A1

Researchers have identified the structure of a special transporter found in red blood cells and how it interacts with drugs. Details on the findings could lead to the development of more targeted medicines. The research team found that this transporter facilitates the movement of a substance called bicarbonate, which certain drugs can inhibit. They discovered how these drugs block the transporter and devised novel compounds capable of achieving the same effect. Researchers at the Icahn School of Medicine at Mount Sinai have identified the structure of a special transporter found in red blood cells and how it interacts with drugs. Details on the findings, which were reported in the September 7 issue of Nature Structural & Molecular Biology, could lead to the development of more targeted medicines. The research team, led by Daniel Wacker, PhD, Bin Zhang, PhD, and Avner Schlessinger, PhD, found that this transporter facilitates the movement of a substance called bicarbonate, which certain drugs can inhibit. They discovered how these drugs block the transporter and devised novel compounds capable of achieving the same effect. "Our findings provide a detailed understanding of how bicarbonate transporters work, and the newly identified tool compounds open doors to studying conditions involving red blood cells, including hemolytic anemias," says Dr. Wacker, corresponding author and an Assistant Professor of Pharmacological Sciences, Neuroscience, and Genetic and Genomic Sciences at Icahn Mount Sinai. Previously, human bicarbonate transporters were poorly understood, despite being involved in many aspects of human physiology, including regulating pH that involves keeping the level of acidity within a specific range. Using cryo-electron microscopy, the team identified high-resolution structures revealing bicarbonate and inhibitor binding, and their impact on the transport mechanism. With these insights, the researchers used computer simulations to analyze millions of compounds that could interact with the substrate binding site. Their experiments pinpointed a group of innovative chemical inhibitors specifically designed for anion exchanger 1, a protein that is crucial for maintaining the proper function of the blood and red blood cells. "Our study also demonstrates the potential for developing new inhibitors with medical potential for other solute carrier (SLC) proteins, a protein family gaining importance in drug development," says co-author Dr. Zhang, the Willard T.C Johnson Research Professor of Neurogenetics and Director of the Mount Sinai Center for Transformative Disease Modeling at Icahn Mount Sinai. Next, the researchers plan to expand their studies to other SLC proteins involved in a variety of disorders including neurodegenerative diseases, psychiatric maladies, and cancer. "This study effectively paves the way to using atomic-level insights toward the rapid development of promising drug-like molecules for SLC proteins," says co-author Dr. Schlessinger, Associate Professor of Pharmacological Sciences and Associate Director of the Mount Sinai Center for Therapeutics Discovery at Icahn Mount Sinai. The paper is titled "Substrate binding and inhibition of the anion exchanger 1 transporter." Additional co-authors, all with Icahn Mount Sinai except where indicated, areMichael J. Capper, PhD; Shifan Yang, PhD; Alexander C. Stone; Sezen Vatansever, MD, PhD (Amgen); Gregory Zilberg, PhD Candidate; Yamuna Kalyani Mathiharan, PhD; Raul Habib, (University of California, Berkeley); Keino Hutchinson, PhD; Yihan Zhao, PhD Candidate; Mihaly Mezei, PhD; and Roman Osman, PhD. The project was supported by National Institutes of Health grants R35GM133504, R01GM108911, U01AG046170, RF1AG057440, R01AG068030, R01DK073681, R01DK067555, R01DK061659, T32GM062754, T32DA053558, as well as a Sloan Research Fellowship in Neuroscience, an Edward Mallinckrodt, Jr. Foundation Grant, and a McKnight Foundation Scholars Award.

PRINCETON, N.J., July 9, 2018 /PRNewswire/ -- Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, announced today that it has received notice of allowance for European (application No. 12786638.2) and Canadian (application No. 2836273) patent applications further extending protection around ThermoVax® including coverage of the Company's ricin toxin vaccine, RiVax®. ThermoVax® is a proprietary vaccine heat stabilization platform technology and the patent, titled "Thermostable vaccine compositions and methods of preparing same," has been previously allowed in Japan, Australia and New Zealand with applications pending in China, United States (US) and other worldwide jurisdictions. The issued patent is complementary to previous patents, including US patents 8,444,991 granted on May 21, 2013 and 8,808,710 granted on August 19, 2014, that include claims for methods of making stabilized vaccines and their attendant compositions. In this new patent, the main claims cover formulations of Soligenix's proprietary thermostabilized ricin toxin vaccine, RiVax®. The thermostable formulation of RiVax® has been shown to be stable for at least 12 months at temperatures up to 40 degrees Celsius (104 degrees Fahrenheit) and to provide 100% protection to non-human primates exposed to aerosol ricin challenge in preclinical studies. Recent developments in the RiVax® program have also described immune correlates of protection for the ricin toxin vaccine, which are important to facilitating potential approval of thermostabilized RiVax® via the US Food and Drug Administration (FDA) "Animal Rule". As a biodefense vaccine, RiVax® also has the potential to qualify for a priority review voucher (PRV) upon FDA approval. Recent PRVs have sold for as much $350 million. "Soligenix continues to advance its RiVax® program with funding from the US government." stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "Soligenix is a world leader in ricin toxin vaccine development, with a Phase 2 clinical trial planned to begin this year." About Ricin Toxin Ricin toxin is a lethal plant-derived toxin and potential biological weapon because of its stability and high potency, and the fact it is readily extracted from by-products of castor oil production. Ricin comes in many forms including powder, mist or pellet. Ricin can also be dissolved in water and other liquids. The US Centers for Disease Control and Prevention estimates that the lethal dose in humans is about the size of a grain of salt. Ricin toxin illness causes tissue necrosis and general organ failure leading to death within several days of exposure. Ricin is especially toxic when inhaled. Ricin works by entering cells of the body and preventing the cells from making the proteins it needs. Without the proteins, cells die, which is eventually harmful to the entire body. There are currently no effective treatments for ricin poisoning. The successful development of an effective vaccine against ricin toxin may act as a deterrent against the actual use of ricin as a biological weapon and could be used to vaccinate military personnel and civilian emergency responders at high risk of potential exposure in the event of a biological attack. About RiVax® RiVax® is Soligenix's proprietary heat stable recombinant subunit vaccine developed to protect against exposure to ricin toxin. With RiVax®, Soligenix is a world leader in the area of ricin toxin vaccine research. RiVax® contains a genetically altered version of a Ricin Toxin A (RTA) chain containing two mutations that inactivate the toxicity of the ricin molecule. A Phase 1A clinical trial was conducted with a formulation of RiVax® that did not contain an adjuvant. This trial revealed dose dependent seroconversion as well as lack of toxicity of the molecule when administered intramuscularly to human volunteers. The adjuvant-free formulation of RiVax® induced toxin neutralizing antibodies that lasted up to 127 days after the third vaccination in several individuals. To increase the longevity and magnitude of toxin neutralizing antibodies, RiVax® was subsequently formulated with an adjuvant of aluminum salts (known colloquially as Alum) for a Phase 1B clinical trial. Alum is an adjuvant that is used in many human vaccines, including most vaccines used in infants. The results of the Phase 1B study indicated that Alum-adjuvanted RiVax® was safe and well tolerated, and induced greater ricin neutralizing antibody levels in humans than adjuvant-free RiVax®. In preclinical animal studies, the Alum formulation of RiVax® also induced higher titers and longer-lasting antibodies than the adjuvant-free vaccine. Vaccination with the thermostabilized Alum-adjuvanted RiVax® formulation in a large animal model provided 100% protection (p<0.0001) against acute exposure to aerosolized ricin, the most lethal route of exposure for ricin. The protected animals also had no signs of gross lung damage, a serious and enduring ramification with long-term consequences for survivors of ricin exposure. These results are described in a publication available here. Heat stabilization of RiVax® is achieved with the Company's proprietary ThermoVax® technology, designed to eliminate the cold-chain production, distribution and storage logistics required for most vaccines. The technology utilizes precise lyophilization of protein immunogens with conventional aluminum adjuvants in combination with secondary adjuvants for rapid onset of protective immunity with the fewest number of vaccinations. By employing ThermoVax® during the final formulation of RiVax®, the vaccine has demonstrated enhanced stability and the ability to withstand temperatures at least as high as 40 degrees Celsius (104 degrees Fahrenheit) for up to one year. The development of RiVax® has been sponsored through a series of grants from both National Institute of Allergy and Infectious Diseases (NIAID), and the FDA and ongoing development is sponsored by NIAID contract #HHSN272201400039C. The Phase 2 clinical trial planned for the second half of 2018 is contingent upon exercise of the final option by the US government under NIAID contract #HHSN272201400039C and/or through other funding sources. RiVax® potentially would be added to the Strategic National Stockpile and dispensed in the event of a terrorist attack. RiVax® has received orphan drug designation in the United States and in Europe. As a new chemical entity, an FDA approved RiVax® vaccine has the potential to qualify for a biodefense PRV, which allows the holder accelerated review of a drug application. Approved under the 21st Century Health Cures Act in late 2016, the biodefense PRV is awarded upon approval as a medical countermeasure when the active ingredient(s) have not been otherwise approved for use in any context. PRVs are transferable and can be sold, with sales in recent years ranging between $125 million to $350 million. When redeemed, PRVs entitle the user to an accelerated review period of six months, saving a median of seven months' review time as calculated in 2009. However, the FDA must be advised 90 days in advance of the use of the PRV and the use of a PRV is associated with an additional user fee ($2.7 million in 2017). About Soligenix, Inc. Soligenix is a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need. Our BioTherapeutics business segment is developing SGX301 as a novel photodynamic therapy utilizing safe visible light for the treatment of cutaneous T-cell lymphoma, our first-in-class innate defense regulator (IDR) technology, dusquetide (SGX942) for the treatment of oral mucositis in head and neck cancer, and proprietary formulations of oral beclomethasone 17,21-dipropionate (BDP) for the prevention/treatment of gastrointestinal (GI) disorders characterized by severe inflammation including pediatric Crohn's disease (SGX203) and acute radiation enteritis (SGX201). Our Vaccines/BioDefense business segment includes active development programs for RiVax®, our ricin toxin vaccine candidate, OrbeShield®, our GI acute radiation syndrome therapeutic candidate and SGX943, our therapeutic candidate for antibiotic resistant and emerging infectious disease. The development of our vaccine programs incorporates the use of our proprietary heat stabilization platform technology, known as ThermoVax®. To date, this business segment has been supported with government grant and contract funding from the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA). For further information regarding Soligenix, Inc., please visit the Company's website at . This press release may contain forward-looking statements that reflect Soligenix, Inc.'s current expectations about its future results, performance, prospects and opportunities, including but not limited to, potential market sizes, patient populations and clinical trial enrollment. Statements that are not historical facts, such as "anticipates," "estimates," "believes," "hopes," "intends," "plans," "expects," "goal," "may," "suggest," "will," "potential," or similar expressions, are forward-looking statements. These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements. Soligenix cannot assure you that it will be able to successfully develop, achieve regulatory approval for or commercialize products based on its technologies, particularly in light of the significant uncertainty inherent in developing therapeutics and vaccines against bioterror threats, conducting preclinical and clinical trials of therapeutics and vaccines, obtaining regulatory approvals and manufacturing therapeutics and vaccines, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that it will be able to successfully obtain any further funding to support product development and commercialization efforts, including grants and awards, maintain its existing grants which are subject to performance requirements, enter into any biodefense procurement contracts with the U.S. Government or other countries, that it will be able to compete with larger and better financed competitors in the biotechnology industry, that changes in health care practice, third party reimbursement limitations and Federal and/or state health care reform initiatives will not negatively affect its business, or that the U.S. Congress may not pass any legislation that would provide additional funding for the Project BioShield program. In addition, there can be no assurance as to timing or success of the preclinical/clinical trials of RiVax®, that RiVax® will be approved for the PRV program or the amount for which a PRV for RiVax® can be sold. These and other risk factors are described from time to time in filings with the Securities and Exchange Commission, including, but not limited to, Soligenix's reports on Forms 10-Q and 10-K. Unless required by law, Soligenix assumes no obligation to update or revise any forward-looking statements as a result of new information or future events. View original content: SOURCE Soligenix, Inc.

WEST LAFAYETTE, Ind., Sept. 7, 2015 (GLOBE NEWSWIRE) -- Endocyte, Inc. (Nasdaq:ECYT), today presented the final overall survival (OS) analysis from the Phase 2b TARGET trial evaluating its small molecule drug conjugate (SMDC) vintafolide in combination with docetaxel in patients with FR positive recurrent NSCLC at the World Conference on Lung Cancer in Denver, Colorado. Vintafolide plus docetaxel improved overall survival by 2.7 months in NSCLC regardless of histology (Median OS 11.5 vs. 8.8 months, OS HR=0.86, 95% CI [0.58, 1.26]). In the predefined subset analysis of patients with adenocarcinoma, which expresses higher levels of folate receptor, vintafolide plus docetaxel improved OS by 5.9 months (12.5 vs. 6.6 months, HR=0.72, 95% CI [0.44, 1.16]). OS for vintafolide as single agent was similar to docetaxel (OS 8.4 vs. 8.8 months, HR=1.02, 95% CI [0.70, 1.50]). The study previously reported that the PFS primary endpoint was met, (HR=0.75, 95% CI [0.52, 1.09]) regardless of histology and in the adenocarcinoma subgroup (HR=0.73, 95% CI [0.46, 1.16]). The safety pro the combination arm was consistent with those observed with docetaxel alone and vintafolide alone, though a higher rate of hematologic and peripheral neuropathy adverse events were observed in the combination arm. "The final OS results are consistent with the biology of the folate receptor target, with higher expression levels in the adenocarcinoma subgroup. These data are important in guiding our future studies in NSCLC," said Ron Ellis, president and CEO at Endocyte. "Based on the results to date from the ongoing Phase 1 dose escalation trial of EC1456, we are optimistic that this agent will represent an important improvement in the treatment landscape for NSCLC," said Alison Armour, chief medical officer. EC1456 is a second generation folate-targeted SMDC, which delivers a more potent drug payload at higher doses than vintafolide. About Vintafolide and Etarfolatide Vintafolide is an investigational, proprietary, injectable SMDC consisting of folate (vitamin B9) linked to a potent vinca alkaloid cytotoxic agent, desacetylvinblastine hydrazide (DAVLBH). Vintafolide is designed to selectively target the folate receptor to deliver the anti-cancer agent to the cancerous tissue. Tumors that have high concentrations of the folate receptor are identified by etarfolatide, a non-invasive imaging diagnostic agent. About EC1456 EC1456 is a second generation SMDC consisting of folate (vitamin B9) linked to a potent cytotoxic agent, tubulysin B hydrazide (TubBH). EC1456 includes an advanced spacer/linker to allow for potentially higher dosing in spite of a more potent payload than vintafolide. EC1456 is currently being evaluated in a Phase 1 study in patients with advanced solid tumors (ClinicalTrials.gov Identifier: NCT01999738). About Endocyte Endocyte is a biopharmaceutical company and leader in developing targeted small molecule drug conjugates (SMDCs) and companion imaging agents for personalized therapy in cancer and other serious diseases. Endocyte uses its proprietary technology to create novel SMDCs and companion imaging agents for personalized targeted therapies. The company's SMDCs actively target receptors that are expressed or over-expressed on diseased cells, relative to healthy cells. This targeted approach is designed to enable the treatment of patients with highly potent drugs into these cells. The companion imaging agents are designed to identify patients whose disease expresses the molecular target of the therapy and who therefore may be more likely to benefit from treatment. For more information, visit . Endocyte Forward-Looking Statement Certain of the statements made in this press release are forward looking, such as those relating to the company's future development plans and those relating to possible future clinical trial results. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include risks that early stage clinical data may not be indicative of subsequent clinical data, that trials of earlier stage agents may not be successful or may take longer to complete than anticipated, and that actual cash needs and financial results may differ from the Company's expectations. More information about the risks and uncertainties faced by Endocyte, Inc. is contained in the company's periodic reports filed with the Securities and Exchange Commission. Endocyte, Inc. disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. CONTACT: Stephanie Ascher Stern Investor Relations, Inc. (212) 362-1200 stephanie@sternir.com jobs and post your resume.