We even have John Hopkins and Duke Medical Centers in our corner.
• Under our license agreement, as amended, with Johns Hopkins University (“JHU”), JHU has granted us an exclusive, worldwide license, under its patents relating to flow sorting of stem cell populations based on a fluorescent ALDH substrate (the “JHU Patents”). Under the terms of the JHU license agreement, as amended, we are obligated to pay a 3% royalty on revenues relating to therapeutic products based on the JHU Patents, and up to 7% on revenues relating to other products based on the JHU patents, subject to an annual minimum of $10,000. We must also pay up to $222,500 in the aggregate upon the satisfaction of specified development milestones. The Company bears all costs to maintain the patents. This agreement terminates with the expiration of the patents in 2016.
• Under our license agreement with Duke University (“Duke”), Duke has granted us an exclusive, worldwide license under its patents and applications that relate to methods for isolating and manufacturing ALDHbr cell populations (the “Duke Patents”). Under the terms of the Duke license agreement, we are obligated to pay up to a 1% royalty to Duke on all revenues relating to the Duke Patents, subject to an annual minimum or $5,000 (which will increase to $25,000 upon the achievement of specified development and commercialization milestones). The Company bears all costs to maintain the patents. This agreement terminates with the expiration of the patents in 2018.
First Stroke Patients in Florida Treated in Miller School Stem Cell Trial
"Yavagal performed Anderson’s study procedure on January 11, making him the second person to be enrolled in the University of Miami/Jackson Memorial Hospital arm of the nationwide trial known as RECOVER-stroke. Approximately 100 patients in the U.S. will be enrolled and randomized within the trial. About 60 of those patients will receive an intra-carotid infusion of stem cells, while the others will receive a placebo. None will know what they received until the trial’s end. Twenty patients are expected to be enrolled in the Miller School trial".
The first two stroke patients have been enrolled in a phase 2 clinical trial of a revolutionary new treatment for ischemic stroke being conducted at the University of Miami/Jackson Memorial Hospital.
The trial, using a patient’s own bone marrow stem cells, is the first intra-arterial stroke stem cell trial in the U.S., and the two UM/Jackson patients are the first in Florida to participate.
Led by Dileep Yavagal, M.D., assistant professor of neurology and neurological surgery, the trial is examining the efficacy of ALD-401, derived from bone marrow, to repair and regenerate tissue following an ischemic event.
James Anderson, a physical education teacher from Maine, is hopeful that participating in the double-blind study will help him recover more quickly. “Stroke is not an easy problem. I liked something that was progressive and I could be involved in.”
Four days before Christmas, Anderson and his wife Barbara had just arrived in Naples to visit his mother-in-law when he suddenly grew very pale. Having run three miles the day before, they had no warning that he was having a major stroke. Anderson was given tissue plasminogen activator (tPA) at a West Coast hospital, but was soon airlifted to Jackson Memorial Hospital, a comprehensive stroke center, because of the severity of the stroke. That’s when Yavagal, who is also Director of Interventional Neurology at UHealth, visited the 58-year-old to explain the study.
Once either tPA is administered to break up a blocked artery or a clot-removal procedure is performed, there are no approved therapies for persisting neurological disabilities seen in a significant number of stroke patients despite treatment and rehabilitation. Yavagal believes ALD-401, which is derived from ALDHbr cells isolated from bone marrow and is injected within weeks of a primary ischemic stroke, has the potential to be one. Manufactured by Aldagen, a wholly-owned subsidiary of Cytomedix, Inc., ALD-401 contains all cell types thought to repair and regenerate tissue following an ischemic event and offers multiple mechanisms of action.
The middle school teacher’s wife, Barbara, said they discussed it with the family and she and James “felt it was right and a way to help others as well…. We really want to be in on the beginning of this so others can benefit.”
Yavagal performed Anderson’s study procedure on January 11, making him the second person to be enrolled in the University of Miami/Jackson Memorial Hospital arm of the nationwide trial known as RECOVER-stroke. Approximately 100 patients in the U.S. will be enrolled and randomized within the trial. About 60 of those patients will receive an intra-carotid infusion of stem cells, while the others will receive a placebo. None will know what they received until the trial’s end. Twenty patients are expected to be enrolled in the Miller School trial.
Yavagal is a leader in research of the intra-arterial delivery of stem cells for stroke and has been funded for this research over the last four years. He works in close collaboration with Joshua M. Hare, M.D., Director of the Interdisciplinary Stem Cell Institute, to translate the promise of stem cells for stroke patients. He is on the national steering committee of the RECOVER-Stroke trial.
With intra-arterial delivery, the cells are delivered directly to the brain via the carotid artery, avoiding their becoming trapped in the lungs and liver, which occurs when stem cells have been administered intravenously. Yavagal, who is also Co-Director of Endovascular Neurosurgery and a faculty member of the Interdisciplinary Stem Cell Institute, says this trial is “hugely significant” because of its delivery method. Despite the availability of tPA and clot-removal procedures, fewer than 40 percent of stroke patients regain their independence.
Anderson was left paralyzed along his left side but can speak. The first person to be enrolled, a 60-year-old Hialeah man, is using a walker but has lost his speech for now. The study is blinded, so neither patient knows whether they received the stem cells or not. They will receive MRI and CT scans regularly to monitor their progress.
An avid fisherman, Anderson instills exercise as a way of life to his students. For now, he’s receiving occupational and recreational therapy along with speech and physical therapy. He is hopeful that his rehabilitation and the stem cell treatment will decrease his recovery time, allowing him to return to his “regular life” sooner. Anderson says he finds encouragement from Yavagal. “I’m inspired by him whenever I see him and talk to him. He’s progressive and cares about people.”
University of Miami
Cytomedix, Inc. (OTCQX: CMXI) (the "Company"), a regenerative therapies company commercializing and developing innovative platelet and adult stem cell technologies, announced today the signing of an agreement with NIH to collaborate on a Phase 2 clinical study in patients with intermittent claudication (IC). IC is caused by peripheral arterial disease (PAD), a condition causing reduced flow of blood and oxygen to muscles of the leg. The study is being funded by NHLBI/NIH and managed by the Cardiovascular Cell Therapy Research Network (CCTRN), which is also responsible for enrolling patients. The CCTRN is a network that includes seven centers in the United States with experience and expertise in stem cell clinical trials studying treatments for cardiovascular heart diseases.
The Phase 2 PACE (Patients with Intermittent Claudication Injected with ALDH Bright Cells) study is an 80 patient, double-blind, placebo-controlled clinical trial intended to demonstrate the safety and efficacy of ALD-301 (Bright Cells) in patients diagnosed with IC. The primary endpoints of the study are safety and the change in peak walking time at 6 months compared to baseline. Additionally, changes in leg collateral arterial anatomy, calf muscle blood flow, and tissue perfusion as determined by magnetic resonance imaging (MRI) will be examined. These novel MRI techniques are incorporated into the study to assess perfusion, providing a unique set of data potentially supporting the angiogenic mechanism of Bright Cells. The clinical study has received Investigational New Drug approval from the U.S. Food and Drug Administration (FDA) and is expected to begin enrollment in Q1 2013 upon the Investigational Review Board approvals from the participating centers.
Martin P. Rosendale, Chief Executive Officer of Cytomedix, stated, "We are delighted that the CCTRN has chosen to collaborate with Cytomedix on this study. Our February acquisition of Aldagen and the Bright Cell technology has positioned us well to play a leading role in investigating promising clinical paths in regenerative medicine where there exists significant unmet medical need. We look forward to supplying a highly differentiated personalized cell therapy product to the participating CCTRN centers involved with this important PAD indication. Intermittent claudication is a serious consequence of arteriosclerosis which, if left untreated, will likely progress to pain at rest and possibly open wounds. Our experience with the AutoloGel product and the clinical treatment of lower extremity wounds resulting from CLI has provided us with a full appreciation of the difficult clinical outcomes associated with this compromised patient population. We are hopeful that improvements in lower leg blood flow will lead to increased peak walking time which has been accepted as an FDA approvable endpoint in pivotal Phase 3 trials in IC."
"This is the first randomized clinical trial to look at the benefits of autologous stem cell therapy in PAD patients with IC. It will collect important mechanistic and clinical information on the efficacy and safety of the direct injection of Bright Cells into these patients. It will also evaluate the utility of advanced imaging endpoints that could be used in the future to further understand the impact of novel therapies in this patient population," added Lem Moyé, M.D., Ph.D., professor of biostatistics at the University of Texas School of Public Health, Houston, and co-author of the study protocol.
PAD is a major unmet medical need affecting approximately 8 to 10 million patients in the U.S. IC is a significant subset of the PAD population and is characterized by pain in the lower legs while in motion that resolves upon rest. Critical limb ischemia (CLI) is the advanced form of PAD, and is associated with poor clinical outcomes and increased morbidity. An important goal of medical intervention is to attempt to prevent the progression of patients from IC to CLI. This clinical study builds on the strong data showing increased blood flow and improved clinical status from Cytomedix's previous Phase 1/2 study of ALD-301 in CLI published last year ("A Randomized, Controlled Study of Autologous Therapy with Bone Marrow-Derived Aldehyde Dehydrogenase Bright Cells in Patients with Critical Limb Ischemia" Catheterization and Cardiovascular Interventions 2011). In the PACE study, ALD-301 will be delivered in the same manner, via direct, intramuscular injection in a grid pattern of the affected lower limb. Cytomedix will be responsible for manufacturing ALD-301 for the clinical trial and will have certain rights to data generated during the trial.
About ALD-301/ALDH Bright Cells
ALD-301 is a population of autologous pluripotent stem cells isolated from the patients' bone marrow using Cytomedix' proprietary Bright Cell technology. These adult stem cells express high levels of the enzyme ALDH, an indicator of biological activity in heterogeneous early stage stem cells. Preclinical research suggests that ALD-301 may promote the repair of ischemic tissue damage by producing signaling molecules that are involved in cell recruitment, cell adhesion, and angiogenesis.