Periodic Reporting for period 1 - PARAGON NOVEL VACCINE (Paragon Novel Vaccine (PNV) an effective protection against all serotypes of five deadly bacteria to eradicate Antimicrobial Resistance (AMR))
Période du rapport: 2023-01-01 au 2024-03-31
Antimicrobial Resistance (AMR) is leading to an uncontrolled rise of superbugs. This worldwide threat kills around 1.27 million people/year and it is estimated to increase by 8-fold until 2050, surpassing 10 million deaths/year. Today AMR costs around $30 billion/year to health systems in the EU/USA. According to the CDC, 5 bacteria (Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli and Streptococcus agalactiae) are responsible for 80% of all life-threatening infections in humans and over 60% of deaths. The therapies used to fight superbugs are antibiotics (treatment) and vaccines (prevention). Antibiotics are increasingly more ineffective (4 of the bacteria mentioned are highly resistant to antibiotics) and contribute to AMR growth. The vaccines available only target S.pneumoniae (e.g. Prevenar/Pfizer). Yet, they cover only up to 20 of its 95 known serotypes. Attempts to create vaccines against the other 4 bacteria have failed. The industry ceased developing new antibiotics given their very limited lifetime efficacy against superbugs.
As a society, we are on the verge of going back to the times when simple infections became deadly to humans. If we can’t develop solutions that can overcome the increasing resistance of bacteria, society will be highly vulnerable to these infections again with death rates comparable to those of one century ago.
AMR is a major threat to public health, but resistance is not the cause of human susceptibility to bacteria. Individuals at risk may develop recurrent infections caused by the same bacteria (even the same serotype) without signs of an effective (protective) immunological memory. This indicates that our immune system is not able to develop a protective immune response against bacteria associated with AMR crisis.
At Immunethep we focused on understanding how these bacteria escape from our immune system and discovered a mechanism of immune suppression that is conserved among the 5 bacteria mentioned above.
This mechanism consists of the excretion of a highly immunosuppressive protein, that shifts the host immune response towards an anti-inflammatory state. By blocking this protein, instead of directly addressing the bacteria, we allow the immune system to respond and control the infection without creating pressure on the bacteria, and therefore not inducing resistance.
PNV aims at stopping the progression of AMR and avoiding millions of deaths globally with a single product that provides effective protection against bacterial infections caused by 5 bacteria responsible for 60% of AMR deaths. PNV may become the world’s first vaccine to prevent multiple bacterial infections, including multi-resistant strains. PNV will contribute to significantly reducing bacterial Sepsis, for which there is no effective treatment available on the market.
The project will enable Immunethep to validate its clinical roadmap for Phases 1 and 2 of clinical trials while supporting GMP production of the vaccine and contributing to support the Phase 1 clinical trial with the product. This first-in-human trial is critical to de-risk the project and allow for the entrance of private investors to move forward in the clinical roadmap ahead. The project also aims at validating the clinical roadmap (e.g. Phase 2) for PNV to streamline its approval process and make it reach the market in a timely fashion to maximize its impact.
As a society, we are on the verge of going back to the times when simple infections became deadly to humans. If we can’t develop solutions that can overcome the increasing resistance of bacteria, society will be highly vulnerable to these infections again with death rates comparable to those of one century ago.
AMR is a major threat to public health, but resistance is not the cause of human susceptibility to bacteria. Individuals at risk may develop recurrent infections caused by the same bacteria (even the same serotype) without signs of an effective (protective) immunological memory. This indicates that our immune system is not able to develop a protective immune response against bacteria associated with AMR crisis.
At Immunethep we focused on understanding how these bacteria escape from our immune system and discovered a mechanism of immune suppression that is conserved among the 5 bacteria mentioned above.
This mechanism consists of the excretion of a highly immunosuppressive protein, that shifts the host immune response towards an anti-inflammatory state. By blocking this protein, instead of directly addressing the bacteria, we allow the immune system to respond and control the infection without creating pressure on the bacteria, and therefore not inducing resistance.
PNV aims at stopping the progression of AMR and avoiding millions of deaths globally with a single product that provides effective protection against bacterial infections caused by 5 bacteria responsible for 60% of AMR deaths. PNV may become the world’s first vaccine to prevent multiple bacterial infections, including multi-resistant strains. PNV will contribute to significantly reducing bacterial Sepsis, for which there is no effective treatment available on the market.
The project will enable Immunethep to validate its clinical roadmap for Phases 1 and 2 of clinical trials while supporting GMP production of the vaccine and contributing to support the Phase 1 clinical trial with the product. This first-in-human trial is critical to de-risk the project and allow for the entrance of private investors to move forward in the clinical roadmap ahead. The project also aims at validating the clinical roadmap (e.g. Phase 2) for PNV to streamline its approval process and make it reach the market in a timely fashion to maximize its impact.
The main activities and achievements so far are related to Intellectual Property (IP), Clinical Assessment, Regulatory approval and the preparation for GMP production of PNV.
Concerning IP, a new composition of matter patent was filed in September 2023. This patent will allow us to further extend the current protection of an “umbrella patent” that limits the different ways of blocking the GAPDH immunosuppressive mechanism.
The Clinical Assessment, which is meant to provide data for the Clinical Trials, has been instrumental in further validating in humans the underlying mechanism which supports the science behind the design of the PNV vaccine. These studies have been also important for the assessment of different biomarkers to be used in the clinic. Additionally, it has also provided data that will allow preliminary efficacy indication of the vaccine already in Phase 1 clinical trials.
The work related to the Regulatory activities has also been intense, both with the help of our consultants (Granzer – Regulatory Consulting & Services), and in the interactions with the Irish regulatory agency (HPRA) which led to the Regulatory and Scientific Advice Report where we could validate the work developed so far and the clinical roadmap ahead.
In the preparation of the GMP production of the vaccine, we have had discussions with the prospective suppliers and designed the specifications and procedures for this production.
Concerning IP, a new composition of matter patent was filed in September 2023. This patent will allow us to further extend the current protection of an “umbrella patent” that limits the different ways of blocking the GAPDH immunosuppressive mechanism.
The Clinical Assessment, which is meant to provide data for the Clinical Trials, has been instrumental in further validating in humans the underlying mechanism which supports the science behind the design of the PNV vaccine. These studies have been also important for the assessment of different biomarkers to be used in the clinic. Additionally, it has also provided data that will allow preliminary efficacy indication of the vaccine already in Phase 1 clinical trials.
The work related to the Regulatory activities has also been intense, both with the help of our consultants (Granzer – Regulatory Consulting & Services), and in the interactions with the Irish regulatory agency (HPRA) which led to the Regulatory and Scientific Advice Report where we could validate the work developed so far and the clinical roadmap ahead.
In the preparation of the GMP production of the vaccine, we have had discussions with the prospective suppliers and designed the specifications and procedures for this production.
The most relevant results of the project so far are:
1) A new composition of matter patent filed in September 2023 related to the final formulation of the PNV vaccine ensures stronger protection for the product, not only in terms of scope but also concerning time;
2) The observational studies performed with human blood samples (WP2) allowed defining preliminary thresholds of antibody concentration which correlate with protection from infection and can enable efficacy indication in Phase 1 clinical trial;
3) The validation of the clinical roadmap by the regulatory agency (HPRA) indicates that Phase 1 is following what has been planned, and then we should go directly to a Phase 2 trial, instead of conducting an intermediate Phase 2A trial (as foreseen in the project). This has a significant impact in reducing the time-to-market of the product (up to 2 years) and has no impact on the project since Phase 2 is already outside the scope of the Grant. Moreover, the new clinical roadmap will most probably entail a Phase 3 single pivotal study, a much smaller study than the usual studies at this stage, since a large stack of data will be already collected in Phase 2.
1) A new composition of matter patent filed in September 2023 related to the final formulation of the PNV vaccine ensures stronger protection for the product, not only in terms of scope but also concerning time;
2) The observational studies performed with human blood samples (WP2) allowed defining preliminary thresholds of antibody concentration which correlate with protection from infection and can enable efficacy indication in Phase 1 clinical trial;
3) The validation of the clinical roadmap by the regulatory agency (HPRA) indicates that Phase 1 is following what has been planned, and then we should go directly to a Phase 2 trial, instead of conducting an intermediate Phase 2A trial (as foreseen in the project). This has a significant impact in reducing the time-to-market of the product (up to 2 years) and has no impact on the project since Phase 2 is already outside the scope of the Grant. Moreover, the new clinical roadmap will most probably entail a Phase 3 single pivotal study, a much smaller study than the usual studies at this stage, since a large stack of data will be already collected in Phase 2.