Paul Stephen Marinec
Senior Scientist, Reflexion Pharmaceuticals
Beyond Biologics: Targeting VEGF-A with Synthetic D-Proteins
Small proteins have historically been under-utilized as human therapeutics because they are rapidly metabolized, have short half-lives and can be neutralized by anti-drug immune responses. However, proteins composed entirely of D-amino acids (“D-proteins”) are resistant to proteases, have longer half-lives and significantly reduced immunogenicity. These properties also enable D-proteins to better penetrate tissues and solid tumors. Because D-proteins are chemically manufactured they can be engineered in ways not possible using biologic manufacturing. Mirror image phage display technology was used to create D-proteins that are potent inhibitors of VEGF-A, an important therapeutic target for treating cancer and eye diseases. This presentation will focus on the development of D-protein inhibitors to VEGF-A.
Dr. Marinec is a senior scientist at Reflexion Pharmaceuticals and has over twenty years of experience in biotechnology. He received his B.Sc. in Neuroscience at the University of Michigan. Dr. Marinec then returned to the University of Michigan Medical School to obtain his Ph.D. in chemical biology. For his postdoctoral training, Dr. Marinec received an NIH NRSA fellowship to work with Jim Wells at UCSF on engineering recombinant antibody frameworks capable of intracellular expression for use as next-generation immunotherapeutics. He also constructed a suite of antibodies against the RAS oncoprotein that demonstrated exquisite mutational and conformational specificity, and developed a methodology for delivering these into malignant cancer cells. Immediately prior to joining Reflexion, Dr. Marinec was spearheading a project to engineer antibodies capable of crossing the blood-brain barrier at Denali Therapeutics.