Clinical Milestones
compiled by ARM

March 2012: Organogenesis Inc., announces U.S. FDA approval of GINTUIT,TM a cell-based product that generates new and aesthetically appealing oral gum tissue. GINTUITTM is a cellular sheet that contains human fibroblasts, keratinocytes, human extracellular matrix proteins and bovine collagen. GINTUITTM is the first approval of an allogeneic cell product via the Center for Biologics Evaluation and Research (CBER) arm of the FDA, and the first cell-based technology that is FDA-approved for use in the dental market.

February 2012: Aastrom Biosciences, Inc. initiates patient enrollment in the REVIVE Phase III clinical trial to assess the efficacy and safety of ixmyelocel-T in the treatment of patients with critical limb ischemia (CLI).The study is the largest randomized, double blind, placebo- controlled, multicenter trial ever conducted, with more than 80 sites in the U.S. including 594 CLI patients who have no option for revascularization. The trial’s primary endpoint is amputation-free survival at 12 months.

February 2012: Baxter International Inc. announces the initiation of a Phase III pivotal clinical trial to evaluate the efficacy and safety of adult autologous CD34+ stem cells to increase exercise capacity in patients with chronic myocardial ischemia (CMI). Progenator Cell Therapy, LLC is Baxter’s manufacturing partner for this trial.The study is enrolling approximately 450 patients across 50 clinical sites in the U.S.

February 2012: StemCells, Inc. announces the FDA has authorized the initiation of a Phase I/II clinical trial of the company’s proprietary HuCNS-SC® product candidate (purified human neural stem cells) in dry age-related macular degeneration (AMD), the most common form of AMD. The company’s human neural stem cell platform is now being studied for all three elements of the central nervous system: the brain, spinal cord and eye.The trial is an open- label, dose-escalation study, and is expected to enroll a total of 16 patients. Preclinical data submitted as part of the company’s IND application demonstrated that HuCNS-SC cells protect host photoreceptors and preserve vision in a well-established animal model of retinal disease that is relevant to dry AMD.

February 2012: Zimmer Holdings, Inc. and ISTO Technologies, Inc., announce a Phase III clinical study to evaluate DeNovo® ET Engineered Tissue Graft, an engineered cartilage implant for the repair of cartilage defects in the knee. DeNovo ET Graft is being developed under a collaborative relationship between ISTO and Zimmer.The Phase III study comprises a randomized, controlled clinical trial involving 225 patients at up to 25 centers in the U.S.The program is designed to demonstrate superiority over the current standard of care (microfracture) for articular cartilage defects.

January 2012: Advanced Cell Technology, Inc. (ACT) announces Phase I/II clinical data published in The Lancet demonstrating the safety of ACT’s human embryonic stem cell (hESC)-derived retinal pigment epithelium cells for the treatment of Stargardt’s macular dystrophy and dry age-related macular degeneration. Results were reported for two patients, the first in each of the Phase I/II clinical trials. In addition to showing no adverse safety issues, structural evidence confirmed that the hESC-derived cells survived and continued to persist during the study period reported. Both patients had measurable improvements in their vision that persisted for more than four months.

January 2012: Amorcyte, LLC, a NeoStem, Inc. company, announces the enrollment of the first patient in the Amorcyte PreSERVE Phase II trial for acute myocardial infarction. The study is a multicenter, randomized, double blind, placebo-controlled clinical trial to evaluate the safety and efficacy of infarct-related artery infusion of AMR-001, an autologous bone marrow derived cell therapy enriched for CD34+ cells. Approximately 160 subjects, age 18 and older, will be enrolled. Progenitor Cell Therapy, also a NeoStem company, is supporting the manufacturing, product supply and logistics for the trial.

January 2012: AxoGen, Inc. reports that the Avance® Nerve Graft is achieving meaningful recovery in 87 percent of patients with peripheral nerve injuries. The study is being conducted at 12 leading U.S. surgical sites and led by the Buncke Clinic in San Francisco. It is also the first multi-center clinical trial on processed nerve allografts. A summary of the findings have been published in the January 2012 issue of Microsurgery.

January 2012: Cytori Therapeutics receives an Investigational Device Exemption (IDE) approval from the U.S. FDA to begin the ATHENA trial to investigate the use of the Celution® System, a medical device to prepare adipose-derived stem and regenerative cells (ADRCs) to treat chronic myocardial ischemia (CMI). The trial is enrolling up to 45 patients who have limited therapeutic options.The study is evaluating clinical and
functional outcomes, including safety, peak oxygen consumption (mVO2) and clinical outcomes at 12 months.

January 2012: Sangamo BioSciences, Inc. an- nounces the initiation of two new Phase II clinical studies in its program to develop a “functional cure” for HIV/AIDS. Sangamo’s ZFPTherapeutic® approach generatesT-cells that are resistant to HIV infection using its zinc finger nuclease technology to permanently disrupt the DNA sequence encoding CCR5, a co-receptor used by HIV to enter cells. In Sangamo’s Phase I trial, the viral load of an SB-728-T treated-subject de- creased to undetectable levels during a sched- uled treatment interruption.The research and pre-IND work is supported through a collabora- tion with scientists at City of Hope and the University of Southern California, under a $14.5 million CIRM DiseaseTeam Research Award.

November 2011: Harvard Bioscience, Inc., a developer of tools to advance regenerative medicine, announces that its “InBreath” bioreactor was used for the world’s second successful transplantation of a synthetic tissue- engineered windpipe at the Karolinska University Hospital in Stockholm, Sweden—the tracheas
in both procedures were grown in Harvard Bioscience’s bioreactors. Patient-derived cells were grown on the scaffold inside the bioreactor for two days before transplantation.

November 2011: Mesoblast’s Phase II 60-patient clinical trial results show that RevascorTM increases blood supply to damaged heart muscle. After one year of treatment RevascorTM reduces the rate of major adverse events including heart attack, cardiac death and need for artery clearing procedures by 78% when compared with patients who received the current standard of care.

September 2011: ReNeuron announces that the Pilot Investigation of Stem Cells in Stroke (PISCES) trial’s independent Data Safety Monitoring Board recommends that the ReN001 stem cell therapy trial for disabled stroke patients advance to the evaluation of a higher dose of cells based on safety data from the first dose cohort of three patients treated with ReN001. In this Phase I single administration, dose escalation study, ReNeuron’s stem cell therapy is being administered to a total of 12 stroke patients who have been left disabled by an ischemic stroke.The PISCES study is the world’s first fully regulated clinical trial of a neural stem cell therapy for disabled stroke patients.

August 2011: Healthpoint Biotherapeutics announces positive top line results for its Phase IIb clinical trial investigating the efficacy of HP802-247 in venous leg ulcers. HP802-247 is an investigational allogeneic living cell suspension containing keratinocytes and fibroblasts. Overall, HP802-247 is achieving statistical significance, as compared with control plus standard care, with the safety profile of the active groups being similar to placebo.

May 2011: Aldagen, Inc. announces Phase I/ II clinical trial results for ALD-301, a stem cell therapy being developed as a treatment for critical limb ischemia.The Phase I/II study is a multi-center study and includes Cardiology PC, Duke University,Texas Heart Institute and St. Joseph’s Research Institute.The Phase I/ II double-blind study includes a total of 21 subjects.The primary objective of the trial is to evaluate the safety of ALD-301. Overall, ALD- 301 is showing to be well tolerated, with no therapy-related adverse events and also shows significant improvements in three efficacy endpoints compared to baseline at 12 weeks.

April 2011: Juventas Therapeutics announces completion of its Phase I clinical trial evaluating the safety and preliminary efficacy of JVS-100 for treatment of patients with heart failure.The trial included 17 NYHA Class III heart failure patients. Results from several pre-clinical studies demonstrated cardiac repair following
a myocardial infarction through activation of natural stem-cell repair pathways, promotion of new blood vessel formation and prevention of ongoing cell death.

March 2011: Athersys, Inc. announces the initiation of patient enrollment, and dosing of the first patient for a Phase II clinical trial evaluating the safety and efficacy of administration of MultiStem,® Athersys’ allogeneic cell therapy product for the treatment of ulcerative colitis. This Phase II clinical trial is part of a strategic global collaboration between Athersys and Pfizer Inc. to investigate MultiStem for the treatment of inflammatory bowel disease.The trial is being conducted at multiple clinical sites in North America and Europe, and will include up to approximately 126 patients.

March 2011: StemCells, Inc. announces the initiation of a Phase I/II clinical trial of its proprietary HuCNS-SC® human neural stem cells in chronic spinal cord injury.The trial is enrolling 12 patients with thoracic (chest-level) spinal cord injury who have a neurological injury level ofT2-T11, and will include both complete and incomplete injuries as classified by the American Spinal Injury Association (ASIA) Impairment Scale.The trial is being conducted in Switzerland at the Balgrist University Hospital at the University of Zurich, a world leading medical center for spinal cord injury and rehabilitation.