The success of gene therapy requires both an increased understanding of the molecular basis of the target disease and improved technologies to deliver the gene of interest. Adeno-associated virus (AAV) vectors have been a favored delivery vehicle for in vivo gene therapy; however, first generation AAV vectors can have limited utility in many diseases. Improved delivery vehicles (vectors) to shuttle therapeutic genes into the cells of interest in a manner that limits the exposure of non-target organs and increases the efficiency of gene uptake by target organs are needed. Ideally these vectors would be customizable to accommodate the unmet medical needs of patients with a variety of genetic deficiencies resulting in diseases such as hemophilia A and B, muscular dystrophy, and cystic fibrosis.
Using diversity-generating methods initiated at UC Berkeley and expanded upon at 4D Molecular Therapeutics, an initial starting library of ~100 million vectors was developed. This pool, millions of times greater than existing wild type vectors, then goes through a customized selection process. Requiring months of effort, the resulting vectors are optimized for the desired target organ, route of administration, and ability to avoid inhibition by neutralizing antibodies. Following selection, the final product is created by insertion of the therapeutic gene of interest into the vector using well-established methods. Currently, over 10 different discovery processes are underway to support vector development for the potential treatment of cardiovascular, skeletal muscle, retinal, hepatic, CNS and spinal cord diseases.
Dr. Kirn will describe the early research and subsequent development activities at 4D Molecular Therapeutics that have enabled the creation of a diverse product pipeline, and its external validation as evidenced by five collaborations in less than two years, including ones with Pfizer and Roche.
Dr. David Kirn is a physician-scientist, experienced biotech business executive and entrepreneur, and global leader in the design and clinical R&D of viral vector genetic therapies. He was a founder at three successful genetic therapy-viral vector companies, led the development of three novel viral vector-based product platforms resulting in over 10 IND filings, and designed and led roughly 30 clinical trials (Phase 1-3) involving over 800 patients treated with viral vector gene therapies.
At Onyx Pharmaceuticals he was VP, Clinical R&D and the first development employee. During his tenure, the company executed three pharmaceutical partnerships and a successful IPO (eventually sold for ~$10 billion to Amgen). He led over 15 clinical trials involving over 400 patients in Phase 1-3 with an adenovirus-based genetic therapy for cancer. He was then Founder & CEO of Jennerex, a pioneer in oncolytic immunotherapy for cancer with vaccine virus vectors. He successfully raised over $70 million dollars and executed three biotech partnership deals, while leading over 10 clinical trials involving over 250 patients in Phase 1-2b. He sold the company for ~$145 million dollars with earn-out payments. Finally, he co-founded 4D with David Schaffer in 2013. He is also co-Founder and Executive Chairman of Ignite Immunotherapy. In 2013 he was the inaugural recipient of the Johnson & Johnson Entrepreneur-Innovator Award.
Dr. Kirn served as SVP Clinical R&D at Celgene, VP Clinical R&D at Onyx Pharmaceuticals, and consulting clinical project leader for biological therapies at Biogen Idec, Novartis-Cell Genesys, and Intermune.
Dr. Kirn has held academic faculty positions at the University of California, San Francisco (UCSF); Imperial College (London); and the University of Oxford. He co-authored over 100 publications in peer-reviewed journals, including Nature, Nature Medicine, Nature Biotech, Nature Reviews Cancer, Science & Science Translational Medicine.
Dr. Kirn completed a fellowship in oncology at UCSF, internal medicine residency at Harvard Medical School (Brigham and Womenís Hospital), and was chief medical resident at a Harvard teaching hospital. He received his MD from UCSF (AOA Honors) and BA in Physiology from UC Berkeley (Departmental Citation, Phi Beta Kappa).