The first year of the project was used to establish the infrastructure needed to drive three AMR drug development projects. The original GNA NOW portfolio included three natural-product derived assets all exerting a novel mechanism of action on the bacteria. These programmes were NOSO-502 – bringing an odilorhabdin derivative from Late Lead to completed phase 1 study, NOSO-2G – Lead optimisation to find a second generation odilorhabdin with a complementary microbiological profile and/or improved DMPK characteristics, and CORRA – bringing a corramycin derivative from Late Lead to Clinical Candidate stage.
In the second and third year, two of the three original programmes, CORRA and NOSO-2G, received a no-go decision, as they were unlikely to reach the set objective within the GNA NOW project term and budget, thereby de-risking the GNA NOW portfolio. In the fifth reporting period, a patent was submitted for NOSO-2G on “New odilorhabdins analogues as antibiotics against multi-resistant bacteria”.
Despite promising results of preclinical studies of NOSO-502, two major deviations from the CMC plan triggered a No-Go decision. One of GSK's Gram- antibiotic programmes Global Health Infectious Disease (GHID, WP7) was adopted as it fulfilled the criteria for a replacement programme. The Scientific Lead role was transferred to GSK from Evotec, who left the consortium.
In the fifth year, activities in WP7 GHID started. The goal of this WP is to generate enough information through pre-clinical activities in GNA NOW to fully assess the suitability of novel compounds to treat severe bacterial enteric infections in LMICs, primarily paediatric populations, to inform decisions on subsequent progression to clinical phases. GNA NOW’s activities in the fifth reporting period has focussed on selection, collection, and characterisation of relevant strains and developing an antibiotic panel. Several microbiology and PK/PD experiments have been conducted to assess the profiles of standard of care antibiotics to use later as reference. This is preparatory work, to establish baselines and protocols, so that in the next reporting period work with GSK's investigational drug, Gepotidacin, could start.
In the sixth reporting period, three main activities dominated: 1) inter-laboratory quality control of PKPD protocols; 2) microbacterial and PKPD characterization of Gepotidacin to complete its profile for future reference; and 2) establishing a reliable platform with validated methods for testing future compounds for enteric infections, including investigating the translatability of several animal models. To complete these tasks, an extension of the GNA NOW project was requested and approved.
