NEWTON, MA, November 27, 2012—AesRx announced it will present data from the recently completed Phase 1 study of its anti-sickling agent Aes-103 at the 2012 American Society of Hematology (ASH) meeting in Atlanta. The data will be presented in a poster session on December 10.
Data shows the drug is safe and well-tolerated. It also shows Aes-103 is biologically active in humans in a manner consistent with its proposed mechanism of action in sickle cell disease.
The first-in-human, double-blind, placebo-controlled clinical trial was conducted in collaboration with the National Institutes of Health (NIH). The trial examined the effects of single doses of Aes-103 at 300 mg, 1000 mg, 2000 mg and 4000 mg or placebo in 20 healthy normal volunteers of African-American descent. Endpoints were focused on safety, pharmacokinetics and pharmacodynamic changes.
The safety measures showed no clinically significant adverse effects on vital signs, ECGs, clinical laboratory tests, physical exams or adverse events. All adverse events were mild and transient. The pharmacokinetics of Aes-103 showed 5-10 fold higher drug concentrations in red blood cells, which is the site of action of Aes-103 on hemoglobin, compared to drug concentrations in plasma. Aes-103 was rapidly absorbed and the amount of Aes-103 in plasma and red blood cells was largely dose proportional.
Pharmacodynamic effects were also examined to determine the ability of Aes-103 to increase the oxygen affinity of the hemoglobin of the healthy volunteers. In a hypoxia challenge test, the subjects inhaled low levels of oxygen (12%) while their blood oxygen levels (SpO2%) were monitored. Aes-103 in 1000-4000 mg doses reduced the hypoxia-related drop in subjects’ SpO2% compared to placebo and the 300 mg dose.
“We are very pleased with the results of our Phase 1 study,” commented Stephen R. Seiler, AesRx’s Chief Executive Officer. “In sickle cell patients, increasing the oxygen affinity of hemoglobin is known to prevent red blood cell sickling. The ability of Aes-103 to provide protection in a hypoxia challenge of healthy volunteers indicates biological activity in humans in a manner consistent with Aes-103’s proposed mechanism of action in sickle cell disease.”
Based on these positive results, a second trial of similar design enrolling patients with sickle cell disease has been initiated at the NIH Clinical Center in Bethesda, MD and is currently ongoing (see http://www.clinicaltrials.gov/ct2/show/NCT01597401?term=aes-103&rank=1).
The reported Phase 1 study and the ongoing Phase 1/2a study in sickle cell patients are part of a multi-institute, public-private translational research collaboration involving AesRx and two separate NIH components—the National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences (NCATS) through its Therapeutics for Rare and Neglected Diseases (TRND) program.
AesRx is a biopharmaceutical company dedicated to the development of treatments for two orphan diseases. The Company’s lead program (Aes-103) is targeted to the treatment of sickle cell disease. Sickle cell disease is a recessive disorder of the hemoglobin which can lead to a wide range of serious, sometimes life-threatening, conditions including: chronic hemolytic anemia, chronic pain and acute painful crisis, stroke, acute chest syndrome, and cumulative damage to tissues and organs. More than 13 million individuals world-wide are afflicted with sickle cell disease. Aes-103 works by increasing the affinity of sickle hemoglobin for oxygen. Because only red blood cells with no bound oxygen will sickle, increasing the ability of the sickle red blood cells to bind oxygen reduces the number of cells that can sickle. AesRx is developing Aes-103 in collaboration with the National Institutes of Health. AesRx’s second development program, Aes-210, is targeted to treat certain inflammatory diseases of the lower intestine, including distal ulcerative colitis, pouchitis and radiation induced proctitis.
For more information about AesRx and Aes-103, see http://aesrx.com.