Periodic Reporting for period 2 - CureGLIO (Clinical validation of GLIX1: a small molecule that targets epigenetic changes in cancer cells to treat glioblastoma multiforme (GBM), the highest global unmet need in oncology.)
Berichtszeitraum: 2024-01-01 bis 2024-12-31
The prognosis of glioblastoma (GBM) is exceedingly poor. Even with the best available treatment options, a patient is expected to live 16.5 months on average. The front-line drug, Temozolomide (TMZ), improves lifespan by a mere 2.5 months. However, between 50-75% of these patients have tumours that are resistant to TMZ treatment. The other three drugs on the market display even worse improvements in the overall survival rate.
Because of the lack of effective treatment options and the severity of the disease, GBM is often cited as the highest unmet need in oncology. All drugs specifically designed for the treatment of GBM are more than 20 years old and as such are off patent, which reflects the lack of innovation in the GBM space. This is mainly due to the constant failure of the clinical pipeline (97.6% of the candidate drugs failed from 1983 to 2020 and the last approval was in 2004). The alternatives under development are associated with several limitations, including low applicability.
The GLIX family of molecules are designed to treat cancers with high unmet needs — including glioblastoma, pancreatic and ovarian cancers among others. We are presently advancing our lead asset, GLIX1, towards the clinic for the treatment of GBM. Among all the GLIX molecules, GLIX1 shows highest efficacy against GBM and it has the simpler synthesis process, which is highly valued by potential partners.
Through the completion of the killGLIO project, Hemispherian will:
1. Determine the optimal delivery route for GLIX1 (either IV or oral) through additional non-clinical studies.
2. Conduct Phase 1 clinical trials to determine the recommended dose for the Phase 2 clinical trials.
3. Conduct a double-blinded randomized controlled Phase 2 clinical trial, against TMZ, with GBM patients.
Because of the lack of effective treatment options and the severity of the disease, GBM is often cited as the highest unmet need in oncology. All drugs specifically designed for the treatment of GBM are more than 20 years old and as such are off patent, which reflects the lack of innovation in the GBM space. This is mainly due to the constant failure of the clinical pipeline (97.6% of the candidate drugs failed from 1983 to 2020 and the last approval was in 2004). The alternatives under development are associated with several limitations, including low applicability.
The GLIX family of molecules are designed to treat cancers with high unmet needs — including glioblastoma, pancreatic and ovarian cancers among others. We are presently advancing our lead asset, GLIX1, towards the clinic for the treatment of GBM. Among all the GLIX molecules, GLIX1 shows highest efficacy against GBM and it has the simpler synthesis process, which is highly valued by potential partners.
Through the completion of the killGLIO project, Hemispherian will:
1. Determine the optimal delivery route for GLIX1 (either IV or oral) through additional non-clinical studies.
2. Conduct Phase 1 clinical trials to determine the recommended dose for the Phase 2 clinical trials.
3. Conduct a double-blinded randomized controlled Phase 2 clinical trial, against TMZ, with GBM patients.
The overall objective of this project is to undertake all the required activities associated with the GLIX1 clinical validation and business development. Hemispherian has already obtained robust and promising pre-clinical results with GLIX1 using human cancer cell lines and mouse xenograft models. Therefore, the ample pre-clinical data, both in terms of efficacy and safety, support the advance towards first in human clinical studies. However, before the clinical trials, Hemispherian will have to invest in additional pharmacokinetics and toxicology studies to gather all the documentation needed for the investigational new drug (IND) application, including the determination of the route of administration.
The work plan is composed of ten work packages (WPs): WP1-8 from TR5 to 8 and WP9-10 to reach TRL9. The first six WPs are technological and include the non-clinical studies, the development of a CDx assay, and the Phase 1 and Phase 2 clinical trials for validation of GLIX1.
The non-clinical studies for the Development of GLIX1 include the assessment of GLIX1 pharmacokinetics and toxicology in rats, dogs, and human samples, which will enable us to determine the best administration route and the LD10 and, consequently, to gather all the info required to conduct a Phase 1 clinical trial.
WP7 is market-oriented, and it includes a continuous market overview by focusing on strategic information, such as opportunities/competition. Dissemination and Communication activities are also planned to engage with the different stakeholders. Furthermore, structured monitoring of internal processes to ensure the protection of IPR prior to the disclosure is also planned. WP8 is dedicated to project coordination, risk management and contingency planning, and administration and communication with the European Commission.
WP9 is focused on mapping potential partners, preparation of the business development package, and business development activities, paving the way to establish a deal. WP10 is dedicated to establishing a licensing or a partnership deal for efficient market launch and global commercialization.
The work plan is composed of ten work packages (WPs): WP1-8 from TR5 to 8 and WP9-10 to reach TRL9. The first six WPs are technological and include the non-clinical studies, the development of a CDx assay, and the Phase 1 and Phase 2 clinical trials for validation of GLIX1.
The non-clinical studies for the Development of GLIX1 include the assessment of GLIX1 pharmacokinetics and toxicology in rats, dogs, and human samples, which will enable us to determine the best administration route and the LD10 and, consequently, to gather all the info required to conduct a Phase 1 clinical trial.
WP7 is market-oriented, and it includes a continuous market overview by focusing on strategic information, such as opportunities/competition. Dissemination and Communication activities are also planned to engage with the different stakeholders. Furthermore, structured monitoring of internal processes to ensure the protection of IPR prior to the disclosure is also planned. WP8 is dedicated to project coordination, risk management and contingency planning, and administration and communication with the European Commission.
WP9 is focused on mapping potential partners, preparation of the business development package, and business development activities, paving the way to establish a deal. WP10 is dedicated to establishing a licensing or a partnership deal for efficient market launch and global commercialization.
The results obtained through the completion of this project will provide sufficient information for an accelerated market authorisation for GLIX1 under an orphan drug designation. Such an accelerated market authorisation will require the successful completion of IND-studies/filings, Phase I and II clinical trials and meeting FDA/EMA requirements for orphan designation.