Periodic Reporting for period 1 - INGSIGHT (Selective Inhibition of NOTCH by novel γ-Secretase Inhibitors in Tumours)
Reporting period: 2021-04-01 to 2023-03-31
Cancer is a major cause of global mortality, resulting in millions of diagnosed cases and deaths annually. Treatment failure and metastasis are primary factors contributing to cancer-related deaths. The development of resistance to therapies and the limited effectiveness of treatments in relapsed and metastatic cases remain significant challenges. Moreover, the adverse effects on patients' quality of life and normal bodily functions often necessitate dose and duration limitations in cancer treatments, leading to non-durable responses and reduced long-term survival
Our research aims to address these issues by focusing on developing tumour-specific anti-cancer drugs. Such therapies can be administered to cancer patients at high doses and duration without affecting normal tissues. Specifically, we have concentrated on targeting the Notch pathway, which plays a crucial role in many human cancers but is also important in normal tissues. Previous drugs targeting the Notch pathway (i.e Notch inhibitors) have faced limitations due to their impact on normal tissues and are not yet approved for clinical use.
In our project, we have obtained compelling scientific evidence for tumour-specific inhibitors of the Notch pathway that demonstrate minimal side effects even at very high doses. These inhibitors have been designed and developed based on a deep understanding of the differences in Notch signaling between normal and tumour cells. Through one approach, we discovered and developed a molecule that acts as a Notch inhibitor specifically activated by the tumour milieu, a unique environment not present in healthy tissue, thus releasing an active Notch inhibitor. Our findings indicate that these novel inhibitors can be administered to laboratory animals at significantly higher doses and for longer durations compared to clinically failed Notch inhibitors without causing harmful side effects.
Thus, the results from our cell-model based and in vivo analyses are promising, and we remain committed to further developing and improving these inhibitors. Concurrently, we are establishing a spin-out company to secure public-private funding, which will expedite the identification development of a clinical candidate for first-in-human studies within the next 5-10 years.
Our research aims to address these issues by focusing on developing tumour-specific anti-cancer drugs. Such therapies can be administered to cancer patients at high doses and duration without affecting normal tissues. Specifically, we have concentrated on targeting the Notch pathway, which plays a crucial role in many human cancers but is also important in normal tissues. Previous drugs targeting the Notch pathway (i.e Notch inhibitors) have faced limitations due to their impact on normal tissues and are not yet approved for clinical use.
In our project, we have obtained compelling scientific evidence for tumour-specific inhibitors of the Notch pathway that demonstrate minimal side effects even at very high doses. These inhibitors have been designed and developed based on a deep understanding of the differences in Notch signaling between normal and tumour cells. Through one approach, we discovered and developed a molecule that acts as a Notch inhibitor specifically activated by the tumour milieu, a unique environment not present in healthy tissue, thus releasing an active Notch inhibitor. Our findings indicate that these novel inhibitors can be administered to laboratory animals at significantly higher doses and for longer durations compared to clinically failed Notch inhibitors without causing harmful side effects.
Thus, the results from our cell-model based and in vivo analyses are promising, and we remain committed to further developing and improving these inhibitors. Concurrently, we are establishing a spin-out company to secure public-private funding, which will expedite the identification development of a clinical candidate for first-in-human studies within the next 5-10 years.