Dr. Kannan Rangaramanujam, JHU
Development and Translation of Cell-Targeted Systemic Nanomedicines
Abstract: Dendrimers offer unique nanoscale attributes (e.g., surface group density) that can ‘tune’ their interactions with disease tissue and cells. Taking advantage of this, we have developed dendrimers that target reactive microglia/macrophages, ‘injured’ neuronal cells, adipocytes and more, from systemic administration, without a need for targeting ligands or antibodies. Through extensive collaboration with physicians, this has been validated in more than 55 animal models in six species, and human tissue. Building on such selective ‘disease biophysics’ uptake, we have designed dendrimer-drug conjugates which have shown significant promise in clinical trials, addressing decades-old medical challenges, including overcoming the blood-brain barrier and developing systemic treatments for retinal disorders. These results not only provide unique insights into the role of reactive microglia and neurons in disease and repair, but also offer opportunities for developing potent therapies for unmet needs, in many neurological, ocular, and cardiometabolic disorders. Recent efforts to develop new applications in antibody delivery will also be highlighted. Significant, positive outcomes have been seen in six Phase 1 and two phase 2 results. OP-101@ (dendrimer-NAC conjugate), a product developed from his group showed significant promise in Phase 2 trials for severe COVID-19, and was the only drug to address the neurological consequences of COVID-19. Migaldendranib@ (dendrimer-sunitinib analog conjugate), a subcutaneous, once-a-month, cell-targeted therapy showed remarkable results in wet age-related macular degeneration and diabetic retinopathy in Phase 2 trials, addressing a many decade old challenge. Examples of the remarkable promise of this approach in inflammatory, obesity, mental health, retinal, and brain disorders will be discussed.
Biography: Dr. Kannan Rangaramanujam is the Arnall Patz distinguished professor of ophthalmology and co-director of center for nanomedicine at the Wilmer Eye Institute at Johns Hopkins School of Medicine. He is a chemical engineer by training [PhD (Caltech);  BE(Hons.)(BITS, Pilani)]. His research interests are in the field of translational nanomedicine centered on novel approaches to target specific cells at the site of injury. His team has developed and extensively validated the hydroxyl dendrimer and glucose dendrimer platforms through Hopkins-wide collaborations in many animal models of ocular, brain disorders, pain, depression, and cancer. These have the opportunity to address long standing challenges in the field, and will lead to medicines that are easy to administer (e.g., oral pills for AMD and diabetic retinopathy), have minimal side effects, and affordable to large fractions of the world population. He is leading the translation of his research to the clinic, through start-ups and partnerships. He is the co-founder of Ashvattha Therapeutics Inc. and Samata Therapeutics (>$150M raised) – Johns Hopkins spinoffs that are translating some of his team’s patented dendrimer technologies to the clinic, with three products that have completed, or in Phase 2 trials. Dr. Rangaramanujam is an author of >150 patents (issued and pending, licensed), more than 150 peer-reviewed publications, and is supported by significant NIH and federal funding. He has won several recognitions, including fellowship of the American Institute of Medical and Biological Engineers (AIMBE), Controlled Release Society, and Distinguished Alumni Award from BITS (Pilani). He is on the editorial boards of Biomaterials, Advanced Drug Delivery Reviews, and Theranostics.