Driving Therapeutic Innovations: Academic Institutions Can Help Lessen Development Risks

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During the Biotech Week in Boston this past October, I had a chance to talk with David DiGiusto (Stanford University) about his work toward advancing bioprocessing and cell therapy development. I asked him to comment on points from his keynote presentation about how academic research groups can sustainably cycle assets into the biopharmaceutical pipeline. University research departments have long made innovative technologies available for commercial licensing. But in the excerpt below, he details ways in which such groups are further supporting and driving clinical evaluations, derisking potentially life-saving therapeutic candidates, and thereby shortening the time to commercial launch. (You can find the video of our full conversation at http://www.youtube.com/watch?v=5rpCzljZ6tI.)

An Engine for Innovation
Stanford University is an engine for innovation centered in the Silicon Valley. With the large number of investigators at Stanford, we have a vast pipeline of cell and gene therapy applications and products that we hope to move to the market. I originally came to Stanford to develop the infrastructure for translating those cell and gene therapy products to the clinic and, ultimately, to develop them as the standard-of-care treatment for a number of diseases, including cancer, immune disorders, and monogenic diseases and for regenerative medicine. Our infrastructure comprises manufacturing and clinical facilities and programs for staff training. We are developing ways to select products to move into the clinic and reinvest revenues from our industrial partnerships to keep our development engine going.

Dedicated infrastructure, funding, and expertise are essential for moving products forward into the clinic and managing clinical trials. One of our biggest issues is how to prioritize which candidates to move into clinical trials first. We developed algorithms that include maximizing the value of our products when we evaluate them for entry into the queue. For each product, we want to come up with a value proposition that is attractive to our commercial partners down the road. We intend to take these candidates forward through phase 2 clinical trials and proof-of-concept, then partner with the biopharmaceutical industry to develop them further as commercial products.

Regenerative Medicine: Among the products that we are developing are those that will modify hematopoietic stem cells to correct genetic diseases, develop regulatory immune cells or T-regulatory cells, suppress graft-versus-host disease, and treat immune-based disorders such as lupus and type-1 diabetes. We also are working on creating skin grafts for children with epidermolysis bullosa, a devastating skin disease in which a patient’s skin falls off because that person doesn’t produce collagen 7. We are making good progress, but we need to expand it from a clinical experiment to a standard of care so that we can treat more patients. Additional applications may include creating skin grafts for burns and other types of wounds.

We are developing gene therapies for treating thalassemia, sickle cell anemia, and other diseases that require correction of a monogenic defect (a condition in which one gene is defective). These include both ex vivo manipulations (requiring removal and retransplantation of a patient’s cells) and in vivo delivery (directly injecting a gene-carrying virus to correct a disease).

Stanford Hospital, the Lucile Packard Children’s Hospital, and the Stanford School of Medicine together are supporting early development by covering the cost of translating products to the clinic and providing the clinical space to conduct the trials. Through initial testing, we hope to demonstrate safety and proof-of-concept or efficacy. These candidates then can be moved to commercial entities for further development.

One big difference between traditional therapeutics — whether they be chemotherapy, radiation therapy, or small molecules — and these new therapies is how long treatment lasts. When you administer a traditional drug or treatment, as soon as that drug leaves the body or the x-ray beam is turned off, the treatment ends. What we are proposing with cellular therapeutics is a long-lasting curative therapy that engineers an immune system to provide a corrective activity. A single treatment might lead to a life-long cure or long-term treatment that would have to be readministered only over long time intervals. For example, we previously worked on a gene therapy for HIV in which transplanted cells provide patients with a source of HIV-resistant T-cells. Patients with such genes engineered to prevent viral infection would never become immunodeficient and thus never succumb to an infectious disease — the usual cause of death for an HIV patient. The hope is that we can provide long-term treatments and take compliance out of the picture: A cell therapy has an advantage over a traditional therapy in that it is designed to be either curative with one dose or require very few doses and little to no patient compliance with ongoing therapy administration. Therefore, rather than relying on a generic approach, a customized approach to treat disease is the essential basis for precision medicine.

David DiGiusto, PhD, is the executive director of stem cells and cellular therapeutic operations at Stanford University and Stanford Hospital and Clinic. He has spent the past 25 years developing cells as therapeutic agents, specifically for the next generation of treatments for neoplastic monogenic diseases and for regenerative medicine; [email protected].

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