Periodic Reporting for period 4 - GNA NOW (NOVEL GRAM-NEGATIVE ANTIBIOTIC NOW)
Okres sprawozdawczy: 2022-07-01 do 2023-06-30
Antimicrobial Resistance (AMR) is a global and serious threat to human health. Gram-negative bacteria are widely regarded as the culprit representing one of the gravest dangers. Indeed, there is a dearth of new agents able to address AMR in Gram-negative bacteria, especially compounds with novel modes of action. Finding and developing such compounds represents a huge scientific challenge, one that requires the collaboration of stakeholders bringing many different kinds of expertise. The world is coming together to tackle this issue and public-private partnerships represent an attractive way to hasten the pace and increase the probability of successfully identifying and developing novel antibiotics.
Under the global umbrella of the AMR Accelerator, the Gram-Negative Antibacterials-NOW (GNA NOW) consortium pledges to a 6 years’ commitment bringing together key European academic and private experts in antibiotic discovery and development in order to support and manage a portfolio of novel mode of action drugs against Gram-negative bacteria. Starting with three initial compounds/series, dedicated project teams are working together to define and execute the most efficient project plans.
The consortium has put in place robust governance and management structures to ensure that the most promising compounds are pursued diligently, with clear stage gate criteria, and processes for suspending, replacing and recruiting programmes. Ultimately, the goal of GNA NOW is to progress one compound through completion of Phase I studies plus one compound reaching Investigational New Drug (IND) stage and/or up to two compounds reaching clinical development candidate stage.
Under the global umbrella of the AMR Accelerator, the Gram-Negative Antibacterials-NOW (GNA NOW) consortium pledges to a 6 years’ commitment bringing together key European academic and private experts in antibiotic discovery and development in order to support and manage a portfolio of novel mode of action drugs against Gram-negative bacteria. Starting with three initial compounds/series, dedicated project teams are working together to define and execute the most efficient project plans.
The consortium has put in place robust governance and management structures to ensure that the most promising compounds are pursued diligently, with clear stage gate criteria, and processes for suspending, replacing and recruiting programmes. Ultimately, the goal of GNA NOW is to progress one compound through completion of Phase I studies plus one compound reaching Investigational New Drug (IND) stage and/or up to two compounds reaching clinical development candidate stage.
The first year of the project was used to establish the infrastructure needed to drive three AMR drug development projects by forming all governance bodies, electing external advisors and identifying and consulting a public-patient interaction panel, which was maintained in the second year. The original GNA NOW portfolio included three natural-product derived assets all exerting a novel mechanism of action on the bacteria. As such, they were intended to be complementary to existing treatments and less susceptible for interfering resistance development. The three original 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, it was identified that two of the three programmes were unlikely to reach the set objective within the GNA NOW project term and budget. As a measure to de-risk the GNA NOW portfolio, the programmes were suspended and a process to identify an additional programme was developed and deployed as described in PR3. Slightly later, at the end of the previous reporting period, Evotec disclosed to the consortium that they intended to withdraw from their commitments as the GNA NOW Scientific Lead. Different scenarios for the future of the project were developed and assessed. The most attractive one, was to find a replacement industry partner (EFPIA or Associated Partner) with a viable programme that would fit the GNA NOW objectives and which would benefit from the consortium's expertise. A match was found in one of GSK's Gram- antibiotic programmes. The change of scientific lead, the accession of GSK to the consortium, and the adoption of the partner and the associated new programme has been the focus in past year.
Good progress has been recorded with the NOSO-502 programme, with the last period devoted to CMC activities (synthesis of the GMP batch). Unfortunately, there are two major deviations to the plan: the first batch of drug product is slightly smaller than anticipated and delays in the synthesis of the second batch of drug substance. This is delaying the preparation of phase 1 clinical studies and the consortium has therefor also evaluated of the option of conducting a first-in-man micro dosing (aka phase 0) study. However, after evaluation, the Steering Committee endorsed the Core Teams recommendation to not pursue a Phase 0 study.
The NOSO-2G project has been built to provide a second generation of odilorhabdins with an expanded antibacterial spectrum. Before the no-go decision at the end of 2021, a total of 512 analogues were synthesized d and evaluated for their in vitro and in vivo properties. Despite a no-go decision for the program declared during the third period based on anticipated major timelines and cost deviations to achieve candidate selection within the Consortium, promising analogues were identified. The activities during the fourth period have been devoted to data management and to writing of articles and patents.
The third original asset is a compound derived from the natural product Corramycin. In February 2021, the Steering Committee and the General Assembly decided to discontinue the programme. Therefore, the only ongoing activity during year 3 has been dissemination, writing of articles and various communications (congress and posters).
In the second and third year, it was identified that two of the three programmes were unlikely to reach the set objective within the GNA NOW project term and budget. As a measure to de-risk the GNA NOW portfolio, the programmes were suspended and a process to identify an additional programme was developed and deployed as described in PR3. Slightly later, at the end of the previous reporting period, Evotec disclosed to the consortium that they intended to withdraw from their commitments as the GNA NOW Scientific Lead. Different scenarios for the future of the project were developed and assessed. The most attractive one, was to find a replacement industry partner (EFPIA or Associated Partner) with a viable programme that would fit the GNA NOW objectives and which would benefit from the consortium's expertise. A match was found in one of GSK's Gram- antibiotic programmes. The change of scientific lead, the accession of GSK to the consortium, and the adoption of the partner and the associated new programme has been the focus in past year.
Good progress has been recorded with the NOSO-502 programme, with the last period devoted to CMC activities (synthesis of the GMP batch). Unfortunately, there are two major deviations to the plan: the first batch of drug product is slightly smaller than anticipated and delays in the synthesis of the second batch of drug substance. This is delaying the preparation of phase 1 clinical studies and the consortium has therefor also evaluated of the option of conducting a first-in-man micro dosing (aka phase 0) study. However, after evaluation, the Steering Committee endorsed the Core Teams recommendation to not pursue a Phase 0 study.
The NOSO-2G project has been built to provide a second generation of odilorhabdins with an expanded antibacterial spectrum. Before the no-go decision at the end of 2021, a total of 512 analogues were synthesized d and evaluated for their in vitro and in vivo properties. Despite a no-go decision for the program declared during the third period based on anticipated major timelines and cost deviations to achieve candidate selection within the Consortium, promising analogues were identified. The activities during the fourth period have been devoted to data management and to writing of articles and patents.
The third original asset is a compound derived from the natural product Corramycin. In February 2021, the Steering Committee and the General Assembly decided to discontinue the programme. Therefore, the only ongoing activity during year 3 has been dissemination, writing of articles and various communications (congress and posters).
The GNA NOW consortium will have many important impacts:
- Contribute to the development of a vibrant AMR research environment in the EU and more specifically it will leverage public-private synergies: GNA NOW has put together a consortium of experts with complementary expertise, bringing experience from industrial partners in drug development with more specific experience in innovative technologies along the full length of the value chain. As such, beyond the goal of progressing compounds, the EU will benefit from an improvement in expertise and knowledge on AMR.
- Enhance the overall pipeline of medicines for patients with infections caused by multidrug resistant Gram(-) bacteria and advance new and innovative agents, thus improving European citizens' health. Untreatable Gram(-) infections are predicted to lead to an increase in the number of deaths and a huge economical burden.
- Contribute to the EU’s ambition of being a ‘best practice region’ for addressing AMR, through the contribution, aggregation and reuse of appropriate data sets generated within our projects. These data will be combined with historical and project data from parallel AMR Accelerator projects leading to new scientific findings identified by colleagues in Pillar A and the wider network.
- Strengthen the competitiveness and industrial leadership of Europe in a key societal challenge: Two European companies are involved in this project. Moreover, the project is fully in line with the European plan on AMR - European One Health Action Plan against Antimicrobial Resistance (AMR) and with the UN aim of “Sustainable Development Goal 3, ensure health and well-being for all, at every stage of life”.
- Contribute to one of the key IMI2 objectives in Infectious Diseases by improving the current drug development process via dissemination of best-practices, training early career researchers, developing new therapies against antimicrobial resistance and ensuring exchanges with regulators and patients via Patient and Public Involvement (PPI) to bring new priority medicines to patients.
- Further strengthen the role of Patient and Public Involvement (PPI) in preclinical antibacterial research.
- Contribute to the development of a vibrant AMR research environment in the EU and more specifically it will leverage public-private synergies: GNA NOW has put together a consortium of experts with complementary expertise, bringing experience from industrial partners in drug development with more specific experience in innovative technologies along the full length of the value chain. As such, beyond the goal of progressing compounds, the EU will benefit from an improvement in expertise and knowledge on AMR.
- Enhance the overall pipeline of medicines for patients with infections caused by multidrug resistant Gram(-) bacteria and advance new and innovative agents, thus improving European citizens' health. Untreatable Gram(-) infections are predicted to lead to an increase in the number of deaths and a huge economical burden.
- Contribute to the EU’s ambition of being a ‘best practice region’ for addressing AMR, through the contribution, aggregation and reuse of appropriate data sets generated within our projects. These data will be combined with historical and project data from parallel AMR Accelerator projects leading to new scientific findings identified by colleagues in Pillar A and the wider network.
- Strengthen the competitiveness and industrial leadership of Europe in a key societal challenge: Two European companies are involved in this project. Moreover, the project is fully in line with the European plan on AMR - European One Health Action Plan against Antimicrobial Resistance (AMR) and with the UN aim of “Sustainable Development Goal 3, ensure health and well-being for all, at every stage of life”.
- Contribute to one of the key IMI2 objectives in Infectious Diseases by improving the current drug development process via dissemination of best-practices, training early career researchers, developing new therapies against antimicrobial resistance and ensuring exchanges with regulators and patients via Patient and Public Involvement (PPI) to bring new priority medicines to patients.
- Further strengthen the role of Patient and Public Involvement (PPI) in preclinical antibacterial research.