Luis Borges, PhD.Executive Director, Five Prime Therapeutics

Narrative description

Last year, I moved from Amgen to Five Prime to help build the cancer immunotherapy program. This is a relatively new area of research for Five Prime and it will be the main driver for our portfolio in the future. Ever since I arrived at Five Prime, I have been re-building the research pipeline and I have added several new programs. I have implemented novel screening approaches and new global strategies to help diversify our portfolio. We now have a larger number of programs that target both inhibitory and stimulatory pathways in various immune cell subsets. We are currently focused on T cells, both effector and regulatory T cells, NK cells, tumor infiltrating macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs). In addition, my group is exploring different approaches to redirect T cells to eliminate tumor cells using CD3-bispecific antibodies.

My group at Five Prime is responsible for implementing new projects and advancing them from discovery to the IND stage. I have taken advantage of the strengths of our company to de-orphanize immune receptors and ligands in order to build therapeutic candidates that target novel immune checkpoint molecules and co-stimulatory receptors. Our therapeutic candidate molecules are biologics and they include engineered antibodies and in a few cases, soluble ligands or Fc-based constructs containing the extracellular domains of transmembrane proteins. Our antibody candidates include canonical antibodies, ADCC- enhanced molecules and bi-specific antibodies. The Antibody Engineering Group reports directly to me and this group is responsible for the engineering of our candidate antibodies, identifying new industry partners and helping manage our current antibody collaborations with Adimab and Vaccinex.

Besides managing my group, I am part of the senior leadership group at Five Prime; I am a member of the Research Steering Committee, which is responsible for overseeing all research programs at the company. I also work closely with both the Clinical and Business development groups and part of this work involves exploring in-licensing and out-licensing opportunities for both oncology and inflammation programs. I was part of the diligence team that developed the recently announced collaboration with Bluebird for a CAR T cell program and the team that negotiated a clinical collaboration with BMS to explore the combination of our anti-CSF1R antibody and nivolumab. I am also a member of the Joint Steering Committee for a second collaboration with BMS that is focused on two research stage immune-therapy targets.

Prior to Five Prime, I worked at Amgen from 2002 to 2014. At the time when I left Amgen, my group was focused on the development of new immunotherapy approaches to engage different

immune cell subsets to eliminate malignant cells. About half of the group was focused on novel ways to engage co-stimulatory molecules on T and NK cells and the second half was focused on re-direct T cell targeting approaches. Our group was in charge of developing the next generation BiTE (Bi-specific T-cell engager) antibodies for the treatment of cancer and inflammatory conditions. The BiTEs were originally developed by Micromet; they are bispecific scFv’s that re-direct T cells to kill tumors. They have shown significant clinical efficacy in particular for the treatment of hematological malignancies such as ALL and NHL. The BiTE technology became part of the Amgen portfolio when Amgen acquired Micromet in March, 2012. At the time of the Micromet acquisition, I was the scientific leader for the Amgen/Micromet collaboration and shortly after the incorporation of Micromet, my group was assigned the responsibility of engineering and developing the second generation BiTE molecules to better position the platform for use in both liquid and solid malignancies.

During my tenure at Amgen, I was involved in a large number of hematology and oncology programs including pre-clinical discovery programs and clinical stage programs. These programs comprised the development of novel biologic agents that agonize EpoR, the use of human antibodies that target TRAILR and induce tumor apoptosis (AMG655), antibody drug conjugates for the treatment of ovarian cancer, ADCC-engineered antibodies for the treatment of various malignancies, and small molecule inhibitors of IDO to promote anti-tumor immune responses. I supported late stage drug clinical candidates and approved molecules, including Epogen, Aranesp, Neupogen, Neulasta, and Kepivance.

Prior to working at Amgen, I worked at Immunex in projects centered on immunology and cancer immunotherapy. I identified and cloned several members of a new family of immuno-receptor molecules that we named LIRs (Leukocyte Immunoglobulin-like Receptors, also known as ILTs or LILRs). In addition to the LIRs, I did a series of other studies at Immunex to develop cancer immunotherapies based on the modulation of dendritic and T cell functions. These studies relied on the combination of various cytokines including FLT3L and CD40L, to stimulate the adaptive immune system to recognize and kill tumor cells. After Immunex was acquired by Amgen, I moved to the company headquarters in Thousand Oaks, California where I worked for over three years. I gained significant experience at this site dealing with late stage drug development and supporting clinical approved molecules, including Kepivance, a biological agent used for the treatment of oral mucositis. I was part of large project teams involving members from several functions including Clinical, Regulatory, Commercial, Product Development and Safety. My group in Thousand Oaks provided all the non-clinical support to the Kepivance program and I was responsible for all non-clinical materials for filings and reports with regulatory agencies both in the US and overseas. In 2006, I moved back to the Amgen Seattle site to help build the Oncology group and drive new projects focused on the discovery and development of novel biological agents for cancer therapy. In 2011, I transitioned to the newly created Therapeutic Innovation Unit at Amgen where I led a multifunctional program aimed at exploring various immune effector warheads to engineer cancer immune-therapeutic agents.

I have worked in the Biotechnology industry for over eighteen years. I have a strong and proven track record of effectively leading a wide array of projects encompassing diverse groups of scientists, moving molecules through the pipeline and supporting pre-clinical and clinical stage programs. I have significant experience working in matrix organizations and leading major projects where the success depends on effectively bringing together large numbers of scientists and functions and staying focused on the key deliverables and go/no go decision points. I am thoughtful leader, extremely organized, highly motivated and a positive thinker. I am pro-active and I constantly play with different scenarios as I look ahead and build back-up plans to improve the chances for project success. I have worked in large (Amgen), medium (Immunex) and small (Five Prime) size Biotech companies and I have been successful in all environments leading programs and managing large and diverse multifunctional teams.