A) Pre-clinical: The remainder of the IND-enabling studies for the development candidate MSC/VEGF were designed in consultation with Biologics Consulting Group (BCG). The project will begin with the IND-enabling phase and transition through regulatory approvals and through the Phase I clinical trial. The project has a Preclinical unit under the leadership of co-PI Dr. Jan Nolta, and a Clinical unit under the leadership of PI Dr. John Laird. The two units are well integrated, since the team has been meeting frequently since 2008 to plan the testing of the current and prior development candidates. The team is currently performing a Phase I stem cell therapy to test a medical device, as the result of those interactions. During the planning phase we met weekly, and worked continually on the MSC/VEGF project.
Co-PI Jan Nolta, Ph.D. is Scientific Director of the UC Davis/CIRM GMP Facility. Dr. Nolta’s team is expert in translational applications of gene-modified MSC at the level of GLP. The Pre-Clinical team is performing all IND-enabling studies for MSC/VEGF, and will manufacture and qualify the MSC and MSC/VEGF products in the GMP facility at UC Davis that is directed by Dr. Bauer (CMC lead). These studies are ongoing and we have been advised by BCG consulting lead Andra Miller, who was formerly Gene Therapy Group Leader at the FDA, CBER, Division of Cell and Gene Therapies. BCG is assisting with preIND preparation, through the planning grant period funding for this project.
B) Clinical: The Clinical team is led by PI John Laird MD, Medical Director of the UCD Vascular Center, who is an internationally recognized leader in the field of peripheral vascular interventions. He is the PI for multicenter and multinational trials to evaluate novel treatments for peripheral arterial disease. He has led clinical trials investigating the use of FGF-1, Hif, and VEGF to treat claudication and CLI. Christy Pifer is the experienced Project Manager who will guide the entire process. She is the Vascular Center’s clinical trials manager and orchestrates accrual of patients to all trials, including one ongoing Phase I stem cell clinical trial and another pending, as well as a Phase III gene transfer clinical trial. Ms. Pifer has coordinated over 100 Phase I, II and III clinical trials over the past 12 years. The planning grant allowed Ms. Pifer to contribute significant amounts of time to conducting meetings and designing the clinical study with Dr. Laird and other Vascular Center faculty. We had weekly meetings with the clinical and translational team members to finalize the CIRM Disease Team Grant Application.
C) Consultant meetings conducted through the Planning Grant Mechanism:
– Paragon was chosen as our CRO for the proposed trial. We had on-site meetings and conference calls with Paragon during the planning phase.
– Our consultant Dr. Andy Balber, was a Founder, and for ten years served as the CSO of Aldagen, Inc. At Aldagen since 2000, he helped the Company establish and maintain a clinical program during which patients were treated with stem cell products under seven cleared INDs. Dr. Balber has assisted our team with preparation of the preIND application, and will assist with further dialog with the FDA. We met frequently through conference call and email, and he edited our Disease Teams Grant proposal.
– Andra Miller, Director, Cell and Gene Therapy, Biologics Consulting Group, Inc, is a consultant for the development of regulatory strategies to facilitate rapid development of our cell and gene based therap. She and her team are providing support for CMC submission, pre-IND, RAC and IND preparation, Phase I product development strategies and assessment of cGLP compliance. Dr. Miller was Gene Therapy Group Leader for the Division of Cellular and Gene Therapies, Office of Therapeutics of FDA’s Center for Biologics Evaluation and Research, for ten years. We met through conference call and email during the Planning Grant period and she edited our Disease Teams grant application.
Partner PI group: Dr. Herrera from the Reina Sofia Hospital, Cordoba University, Andalucia, is our partner, identified through the planning grant phase. Her team is currently performing clinical trials of MSC injections for CLI using intra-arterial administration. Now, using the strong development candidate MSC/VEGF, the two teams will each embark upon parallel clinical trials in their respective countries, each capitalizing on their own team’s stem cell delivery strengths to patients at the same stage of no option CLI. The two teams will use similar inclusion and exclusion criteria and will work closely together, if funded, to develop Phase I trials that are highly similar except for the route of injection. We had Skype and conference call meetings with interpreters, and frequent email contact during the Planning Grant phase. This partnership would not have been possible without the CIRM Planning Award.