AKAO 2017 Annual Report

17 The C-Scape Phase 1 clinical trial was a double-blind, randomized, placebo-controlled, parallel group study to assess the safety, tolerability and clinical pharmacology of C-Scape, administered orally, in 41 healthy subjects. An overview of the clinical trial data is as follows: • The combination of ceftibuten and clavulanate was well tolerated when administered for 14 days across all dosing regimens tested. • No serious adverse events (“SAEs”), grade 3 or 4 adverse events, or adverse events leading to discontinuation of study drug were observed. • Safety profile was consistent with expectations for ceftibuten and clavulanate when administered based on existing product labels. • The most commonly reported adverse events included vascular access site bruising, headache, diarrhea, gastroenteritis and nausea. The incidence of each of the most common adverse events was comparable between the active treatment groups and placebo. • Preliminary PK following administration of ceftibuten and clavulanate in combination were similar to those following administration of each compound alone, indicating no drug-drug interaction between ceftibuten and clavulanate. • We continue to evaluate safety and pharmacokinetic data and plan to present these at an upcoming scientific and/or investor meeting. Therapeutic Antibody Discovery Program • Antibacterial monoclonal antibodies: Our antibody discovery platform aims to generate antibodies that can treat infections caused by MDR gram-negative pathogens. We have built an antibody discovery platform that allows the rapid identification of rare antibodies that disrupt bacterial membrane biogenesis, leading to bacterial cell death. The platform leverages recent advances in microfluidics, single B cell antibody cloning, and our deep expertise in bacterial genetics, to directly screen millions of single B cells for functional bactericidal antibodies within hours, making rare functional antibody discovery possible. This antibody discovery platform is currently funded, in part, by the Bill & Melinda Gates Foundation. • Other monoclonal antibody programs: In May 2016, we announced that we entered a collaboration and license agreement with Crystal Bioscience (now a wholly-owned subsidiary of Ligand Pharmaceuticals) to identify and develop therapeutic antibodies against multiple novel targets. We are using Crystal Bioscience’s humanized chicken platform to seek to identify therapeutic antibodies to validated human targets that have proved difficult to target utilizing traditional antibody discovery methods in mice. We have initiated antibody discovery efforts on three targets under this agreement. Other Small Molecule Development Programs We continue to work on several research programs related to antibiotics directed against gram-negative MDR bacterial infections in our research group. In November 2017, we announced that we discontinued our work on one of these programs, the LpxC inhibitor research and development efforts, due in part to toxicity of the compounds we were evaluating. Other than the wind-down of these efforts, we do not expect to continue work on LpxC inhibitors at this time. Government and Non-Profit Foundation Contracts and Grants Bill & Melinda Gates Foundation (the “Gates Foundation”) Our therapeutic antibody program utilizes a built-for-purpose discovery platform to identify and develop monoclonal antibodies for the treatment of MDR bacterial infections and other significant unmet medical needs. To further support that program, we entered into a research agreement with the Gates Foundation on May 4, 2017 to n discover drug candidates against gram-negative bacterial pathogens intended to prevent neonatal sepsis i $10.5 developing countries. Pursuant to the Grant Agreement, the Gates Foundation awarded us up to approximately