Oncology
Despite the availability of a number of new targeted therapies, many cancers remain intractable to effective treatment.  FivePrime is using three complementary approaches to find the most medically-relevant growth factors and signaling pathways that drive tumor growth and metastases.

• Targeted screens: While work over the past two decades has identified a number of pathways that are crucial for tumor initiation, growth and maintenance, not all components of these pathways are known.  Our targeted screens are focused on these validated cancer pathways, with the goal of discovering novel ways to modulate these pathways for therapeutic benefit.
• Cell-based screens: Recent research has highlighted substantial differences between primary cancer cells and cancer cell lines.  In addition, it has become increasingly clear that many cancers are driven by sub-populations of cancer initiating cells that have features distinct from the bulk of the tumor, and are resistant to many cancer drugs.   Our cell-based screens are focused on identifying factors that inhibit primary cancer cells as well as specific sub-populations within those tumors.
• In vivo ligand traps:Tumors are products of a complex set of interactions between the cancer cells and their host environment.   To find proteins able to disrupt these interactions, we are using in vivo tumor models to identify extracellular domains that can act as inhibitors of ligands that drive tumor survival, growth, angiogenesis and metastasis.
  

In addition to these screening approaches, FivePrime also uses a variety of bioinformatics and biostatistical approaches to identify pathways and factors that tumors selectively require to grow and metastasize.  Our lead oncology product, FP-1039 and FPT040, were identified using this approach.

Metabolic Diseases
Our initial focus has been on diabetes, where our goal has been to identify proteins capable of modulating the metabolic state in selected cell types, especially properties such as insulin signaling, glucose uptake and lipid homeostasis. Initial assays have uncovered secreted proteins which selectively stimulate glucose uptake in skeletal muscle, and novel proteins that inhibit gluconeogenesis by hepatocytes. Screens in this area are ongoing.  We are also actively developing screens in the area of pancreatic beta cell regeneration.

Recently, FivePrime has expanded its metabolic discovery program beyond diabetes into obesity.  Initial screens in this area are focused on modulating the properties of adipocytes, such as their metabolic rate.

Regenerative Medicine
The ability to repair and re-grow tissues is a promising new frontier of vast potential and is especially suited to protein-based therapeutics given their prominent role in developmental biology.  Based on recent scientific findings that adult stem cells reside in a wide variety of tissues and organs, we are seeking protein factors that can stimulate these progenitor cells to repopulate organs and tissues damaged by disease, injury or aging.  Many of these indications are amenable to local delivery, which may streamline their development and regulatory approval.  Our comprehensive protein library, coupled with our expertise in cell-based assays, uniquely positions us to pursue a wide variety of indications in this field. 

The lead compounds in our regenerative medicine program are FPT033 and FPT057 to treat acute myocardial infarction.  We also have two lead compounds in our epithelial restitution program, FPT042 and FPT046. Both of these compounds are being investigated for intestinal bowel disease and other GI indications.

The table below lists our specific focus areas in regenerative medicine.  

Immunotherapeutics are one of the largest classes of marketed biologics, yet development paths for these products have often been long and circuitous.  Recognizing this challenge, FivePrime is building its immunotherapy screens around product profiles targeted to specific indications and key immunological pathways. 

Our lead product in immunology, FPT025, is a novel secreted cytokine that was identified in an assay designed to find factors that would enhance the proliferation or survival of monocytes.  FPT025 provided an important proof-of-principle that novel proteins within our library could have powerful, but heretofore undiscovered, biological activities. 

Our current screens are focused on rheumatoid arthritis, pulmonary fibrosis and enhancing the response of the innate immune system to treat diseases such as hepatitis C infection.  FivePrime is also developing screens to identify proteins in emerging, high potential areas such as modulation of T-regulatory cells and macrophage subsets.