GEN-004 Shown to Induce Antibody and TH17 Responses
September 6, 2014
Genocea Biosciences, Inc., a biopharmaceutical company developing T cell-directed vaccines and immunotherapies, today presented data from a Phase 1 study of GEN-004, an investigational vaccine designed to prevent disease caused by all serotypes of pneumococcus (Streptococcus pneumoniae) The poster (G-291), titled “Safety and Immunogenicity of a Novel Lipidated Protein Subunit Streptococcus Pneumoniae vaccine,” was presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, DC.
Data presented at ICAAC showed the GEN-004 study met safety, tolerability and immunogenicity goals, including increases in the blood of T helper 17 (TH17) cells, a rare cell type that provides immunity at epithelial and mucosal surfaces. By generating a TH17 T cell-mediated immune response, immunization with GEN-004 may prevent or reduce pneumococcus colonization in the nasopharynx, a precursor to infection caused by all serotypes of pneumoccocus.
The Phase 1 study was a randomized, double-blind, dose-escalation, placebo-controlled clinical trial that enrolled 90 healthy adult volunteers. The primary objective was to evaluate safety and tolerability of GEN-004, which is comprised of three protein antigens, SP0148, SP2108 and SP1912, when administered with and without aluminum hydroxide as an adjuvant. Subjects were randomized to receive 10, 30 or 100µg of each protein/dose with or without 350µg aluminum hydroxide, or placebo, and received three doses, each four weeks apart. GEN-004 was administered by an intramuscular injection.
The study showed that at 85 days after administration, GEN-004 was safe and well tolerated at all doses. The most common side effects were pain, tenderness, muscle aches and fatigue. Most were mild or moderate in intensity. There were no serious adverse events related to the vaccine.
As a secondary objective, the study measured peripheral TH17 levels, by means of IL-17 responses, and IgG (serum antibody) immune responses. IgG responses were observed at all doses tested, both in the presence and absence of the adjuvant. IL-17 responses were observed in the 100 µg dose group and were dependent on the presence of aluminum hydroxide.
The highest dose from this trial of 100µg will be further evaluated in an upcoming Phase 2a study.
GEN-004, Genocea’s second clinical candidate, is a potential universal pneumococcal vaccine designed with insights from the Company’s ATLAS™ platform. GEN-004 contains three unique conserved pneumococcal protein antigens, SP0148, SP1912, and SP2108, shown by ATLAS™ to be associated with TH17 T cell responses against pneumococcus in humans. ATLAS profiles the comprehensive spectrum of actual T cell responses mounted by humans in response to disease, enabling the identification of antigen targets with which to design new vaccines and immunotherapies. The Company plans to initiate a Phase 2a to study GEN-004’s impact on the prevention or reduction of pneumococcus colonization in the nasopharynx in the third quarter of 2014. For more information about GEN-004, please visit http://www.genocea.com/platform-pipeline/pipeline/gen004-for-pneumococcus/.
About Pneumococcus (Streptococcus pneumoniae)
Streptococcus pneumoniae, also known as pneumococcus, is a major cause of infectious disease-related death worldwide. The World Health Organization (WHO) estimates that up to 1.6 million people, including 800,000 children, die each year globally as a result of pneumococcal infection.
Pneumococcus naturally colonizes the nasopharynx, or nose and throat, as a precursor to infection. Pneumococcus causes non-invasive pneumococcal disease (NIPD) when it spreads from the nasopharynx into the upper and lower respiratory system to cause diseases such as otitis media (ear infection) and non-bacteremic pneumonia. When it enters the bloodstream, pneumococcus can cause invasive pneumococcal disease (IPD), including life-threatening illnesses such as sepsis, meningitis and bacteremic pneumonia.
In childhood, immunity to pneumococcus is developed prior to the establishment of protective antibody responses. Scientists believe that this immunity is driven by a rare type of T cells called TH17 CD4+ T cells, which prevent establishment of disease by clearing pneumococcus from the nasopharynx.
Genocea is harnessing the power of T cell immunity to develop life-changing vaccines and immunotherapies. T cells are increasingly recognized as a critical element of protective immune responses to a wide range of diseases, but traditional discovery methods have proven unable to identify the targets of such protective immune response. Using ATLAS™, its proprietary technology platform, Genocea identifies these targets to potentially enable the rapid development of medicines to address critical patient needs. Genocea’s pipeline of novel clinical stage T cell-enabled product candidates includes GEN-003 for HSV-2 therapy, GEN-004 to prevent infections caused by pneumococcus, and earlier-stage programs in chlamydia, HSV-2 prophylaxis, malaria and cancer immunotherapy. For more information, visit www.genocea.com.