Periodic Reporting for period 4 - TIGER (Proof of Principle of the best-in-class therapeutic mRNA cancer vaccine)
Período documentado: 2024-02-01 hasta 2025-07-31
TIGER was planned to deliver proof of principle (PoP) in humans for a novel best-in-class mRNA cancer vaccine platform optimized for intravenous (IV) administration, with the aim to show major clinical efficacy.
The antigens to be used used for the PoP consisted of mRNAs encoding the proteins E6 and E7 of Human Papilloma Virus strain 16 (HPV16), and TriMix mRNAs that stimulate dendritic cells to start strong T cell responses. The mRNAs were to be formulated in a novel patented lipid nanoparticle format shielding the mRNA, and delivering it to immunoactive antigen presenting cells, vastly enhancing T-cell response.
Safety and best-in-class efficacy of our IV mRNA product have been demonstrated in rodent experiments. Furthermore, preclinical to clinical translation has been shown for our TriMix based vaccines using different delivery strategies. Based on the preclinical and prior clinical data, our platform has the potential to cure cancer patients.
The PoP study was to be in patients with recurrent HPV16 positive cancer, which is categorised as a non-communicable disease by the WHO, without and with a PD-1 checkpoint inhibitor. Safety, immunogenicity and clinical benefit will be key endpoints of the study. Biomarker and PROM research will allow future informed therapeutic and care decisions by both patient and care team. Recruitment and stratification plans were put in place. Interactions with regulatory, reimbursement and ethical authorities together with patients and carers were planned to help laying out the route to the patient not only for our product but also for all other mRNA cancer vaccines. The set-up and regulatory approvals were in place for multiple sites. A strategic change in project planning led to the cancellation of the clinical trial.
Additionally, the project encompasses all essential elements for preparing therapy validation in later stage clinical studies, while addressing patient needs, values and choices. Upscaling mRNA vaccine GMP-productionwas planned to enable these further clinical studies. Once validated, our platform was to be easily translatable to a wide range of cancers using other tumour antigens, be they TAAs or neoantigens.
The project successfully developed biomarkers to early stages of testing. This included advances exciting and innovative biomedical diagnostics to provide new tools to support later stage clinical studies, future oncology therapy development and patient stratification. This included a ctDNA assay, radiomics based approaches and immune monitoring. In addition successful outreach work included online and printed materials and a workshop on cancer biomarkers.
The antigens to be used used for the PoP consisted of mRNAs encoding the proteins E6 and E7 of Human Papilloma Virus strain 16 (HPV16), and TriMix mRNAs that stimulate dendritic cells to start strong T cell responses. The mRNAs were to be formulated in a novel patented lipid nanoparticle format shielding the mRNA, and delivering it to immunoactive antigen presenting cells, vastly enhancing T-cell response.
Safety and best-in-class efficacy of our IV mRNA product have been demonstrated in rodent experiments. Furthermore, preclinical to clinical translation has been shown for our TriMix based vaccines using different delivery strategies. Based on the preclinical and prior clinical data, our platform has the potential to cure cancer patients.
The PoP study was to be in patients with recurrent HPV16 positive cancer, which is categorised as a non-communicable disease by the WHO, without and with a PD-1 checkpoint inhibitor. Safety, immunogenicity and clinical benefit will be key endpoints of the study. Biomarker and PROM research will allow future informed therapeutic and care decisions by both patient and care team. Recruitment and stratification plans were put in place. Interactions with regulatory, reimbursement and ethical authorities together with patients and carers were planned to help laying out the route to the patient not only for our product but also for all other mRNA cancer vaccines. The set-up and regulatory approvals were in place for multiple sites. A strategic change in project planning led to the cancellation of the clinical trial.
Additionally, the project encompasses all essential elements for preparing therapy validation in later stage clinical studies, while addressing patient needs, values and choices. Upscaling mRNA vaccine GMP-productionwas planned to enable these further clinical studies. Once validated, our platform was to be easily translatable to a wide range of cancers using other tumour antigens, be they TAAs or neoantigens.
The project successfully developed biomarkers to early stages of testing. This included advances exciting and innovative biomedical diagnostics to provide new tools to support later stage clinical studies, future oncology therapy development and patient stratification. This included a ctDNA assay, radiomics based approaches and immune monitoring. In addition successful outreach work included online and printed materials and a workshop on cancer biomarkers.
- The clinical trial was advanced to start-up ready status. All medicine is ready, the study sites are selected and we have ethical and regulatory approvals in multiple countries.
- eTheRNA decided to stop clinical development of EI-201. The clinical development programme did not advance.
Radiomics worked towards advancing innovative work leading to novel non-invasive biomarker discoveries based on medical imaging. The intention remained to improve individualised patient treatment decision making for HPV positive patients, which are metastatic, treated with immune therapy.
The Amsterdam UMC team developed immune monitoring methodologies to monitor immune responses in women with HPV+ early-stage cervical cancer receiving intratumorally delivered durvalumab, an antibody blocking the PD-L1 immune checkpoint. The proposed immune monitoring studies aimed to provide evidence of the locoregional and systemic biological activity of locally delivered immune checkpoint inhibitors. Ultimately this could provide antitumor efficacy without the immune related adverse events accompanying systemic administration.
SAG developed the SAGAsafe HPV16 assay. this was ready for the analysis of clinical trial samples already during reporting period 1. The lack of clinical samples prevented validation.
- eTheRNA decided to stop clinical development of EI-201. The clinical development programme did not advance.
Radiomics worked towards advancing innovative work leading to novel non-invasive biomarker discoveries based on medical imaging. The intention remained to improve individualised patient treatment decision making for HPV positive patients, which are metastatic, treated with immune therapy.
The Amsterdam UMC team developed immune monitoring methodologies to monitor immune responses in women with HPV+ early-stage cervical cancer receiving intratumorally delivered durvalumab, an antibody blocking the PD-L1 immune checkpoint. The proposed immune monitoring studies aimed to provide evidence of the locoregional and systemic biological activity of locally delivered immune checkpoint inhibitors. Ultimately this could provide antitumor efficacy without the immune related adverse events accompanying systemic administration.
SAG developed the SAGAsafe HPV16 assay. this was ready for the analysis of clinical trial samples already during reporting period 1. The lack of clinical samples prevented validation.
The TIGER project faced significant setbacks during its third and fourth reporting periods, ultimately leading to its early termination in October 2024. The clinical development was halted following eTheRNA’s decision to suspend the EI-201 product, prompting the consortium to seek alternative solutions. Despite initial optimism with a potential new partner the consortium were unable to proceed with the planned clinical activities.
Efforts shifted toward advancing innovative biomarker research by RADIOMICS and VUMC using samples from other HPV16-positive cancer studies. The consortium secured sufficient samples and imaging data for the initial radiomics objectives. The project was closed before this work could be completed.
During RP4, clinical activities in Work Packages (WPs) 1–3 were suspended. WP4 saw some progress, particularly in biomarker and radiomics research, but the early closure prevented full execution.
Updated Impact and Legacy
Biomarker Innovation: Research by RADIOMICS, SAGA and VUMC all have the potential to continue to support improved clinical trial design and patient stratification, accelerating immunotherapy development.
RADIOMICS advances remain aligned with original project goals, offering non-invasive imaging biomarkers for HPV-positive cancers to guide treatment decisions.
Immune Monitoring: VUMC’s data holds promise for future proof-of-concept studies. Although the trial was not advanced, the methodologies developed may be applicable across immunotherapy studies for HPV-related and unrelated cancers.
SAGA Diagnostics: Whilst the assay was developed as planned SAGA was unable to validate its HPV+ assay within TIGER, SAGA continues to lead in offering ultra-sensitive ctDNA analysis for other cancer recurrence and treatment monitoring.
eTheRNA’s mRNA-LNP Progress: Despite the halted clinical trial, eTheRNA made substantial strides in GMP manufacturing and LNP platform development. These advancements support a broad pipeline of mRNA-based therapies and reinforce eTheRNA’s position as a key player in European biotech.
Cancer Vaccine Awareness: TIGER helped elevate the profile of cancer vaccines among regulators, clinicians, and patients, contributing to renewed interest in this therapeutic area and informing stakeholders. Linked rare cancers were highlighted at rare disease showcases. Although no mRNA therapies for cancer have yet received regulatory approval, multiple candidates are in clinical trials, with several in late-stage development.
Efforts shifted toward advancing innovative biomarker research by RADIOMICS and VUMC using samples from other HPV16-positive cancer studies. The consortium secured sufficient samples and imaging data for the initial radiomics objectives. The project was closed before this work could be completed.
During RP4, clinical activities in Work Packages (WPs) 1–3 were suspended. WP4 saw some progress, particularly in biomarker and radiomics research, but the early closure prevented full execution.
Updated Impact and Legacy
Biomarker Innovation: Research by RADIOMICS, SAGA and VUMC all have the potential to continue to support improved clinical trial design and patient stratification, accelerating immunotherapy development.
RADIOMICS advances remain aligned with original project goals, offering non-invasive imaging biomarkers for HPV-positive cancers to guide treatment decisions.
Immune Monitoring: VUMC’s data holds promise for future proof-of-concept studies. Although the trial was not advanced, the methodologies developed may be applicable across immunotherapy studies for HPV-related and unrelated cancers.
SAGA Diagnostics: Whilst the assay was developed as planned SAGA was unable to validate its HPV+ assay within TIGER, SAGA continues to lead in offering ultra-sensitive ctDNA analysis for other cancer recurrence and treatment monitoring.
eTheRNA’s mRNA-LNP Progress: Despite the halted clinical trial, eTheRNA made substantial strides in GMP manufacturing and LNP platform development. These advancements support a broad pipeline of mRNA-based therapies and reinforce eTheRNA’s position as a key player in European biotech.
Cancer Vaccine Awareness: TIGER helped elevate the profile of cancer vaccines among regulators, clinicians, and patients, contributing to renewed interest in this therapeutic area and informing stakeholders. Linked rare cancers were highlighted at rare disease showcases. Although no mRNA therapies for cancer have yet received regulatory approval, multiple candidates are in clinical trials, with several in late-stage development.