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One of the characteristic features of cancer is its ability to evade attacks by the immune system. Recent advances in cancer treatment have been the introduction of immunotherapies, drugs that boost the activity of the immune system to fight cancer. However, there is a large proportion of patients who do not respond to this type of treatment. Therefore, there is a strong need to develop new immunomodulatory drugs that can both increase the efficacy of existing therapies and also make insensitive tumours treatable.
Sprint Bioscience was the first in the world to show that small molecules that inhibit the VpS34 protein lead to increased infiltration of immune cells into the tumour. This is a relatively newly discovered mechanism and we aim to be first-in-class with inhibitors of this protein. The increased infiltration of immune cells inhibits tumour growth and has been shown to increase the efficacy of other immuno-oncology drugs. Patients who respond poorly to immuno-oncology treatment today have been shown to have low immune cell infiltration in the tumour.
The objective of the TREX1 programme, which is in the pre-clinical phase, is to develop drugs that inhibit the TREX1 protein in order to enhance the efficacy of immuno-oncology therapy, radiotherapy and chemotherapy in the treatment of cancer.
Cancer cells often have elevated levels of DNA fragments that have mistakenly ended up outside the cell nucleus. Since DNA fragments outside the nucleus can activate the immune system, cancer cells depend on these DNA fragments being cleaned up quickly - if they are not, the body's immune system will attack the cancer cells.
TREX1 is a protein that breaks down DNA fragments outside the cell nucleus, helping cancer cells to escape the immune system. Scientific studies have shown that there is a link between elevated levels of the TREX1 protein and poorer survival for patients with certain types of cancer, including breast cancer, ovarian cancer
and pancreatic cancer.
The NNMT programme aims to develop drugs that inhibit the NNMT protein for the treatment of solid tumours.
An important aspect of tumour development is that cancer cells can influence their own environment to facilitate tumour growth. This environment is called the tumour microenvironment and is different from the environment around healthy cells in the body. The ability of cancer cells to reprogram healthy cells in the tumour facilitates tumour growth and can prevent the body's immune system from attacking the tumour.
NNMT is a protein that has been shown to be important for this reprogramming of the tumour microenvironment. Sprint Bioscience is developing inhibitors of this target protein to block the growth of cancer cells while increasing the ability of the immune system to attack them. High levels of this target protein have been found in tumours from glioblastoma, ovarian cancer, breast cancer and colorectal cancer, among others. Patients with high levels of this protein have a poorer survival prognosis.
MASH (Metabolic dysfunction-associated steatohepatitis) is a serious liver disease for which there is currently no treatment. In our MASH programme, we are working on a novel mechanism of action and target protein, STK25, which is involved in fat deposition in liver and other tissues, inflammatory response and fibrosis in MASH. This gives us the opportunity to develop treatments that can slow down the progression of both early and late stages of MASLD (Metabolic dysfunction-associated steatotic liver disease)/MASH, either as monotherapy or in combination with other MASH drugs.
The MASH programme was out-licensed to LG Chem in 2019 and a preclinical in vivo proof-of-concept study was conducted in late 2022. The purpose of the study was to study the long-term effect of the new promising compounds developed in the programme. The results showed a reduction in all the parameters used to diagnose MASH and also a reduction in fibrosis in the liver. The study was conducted in a well-established MASH model and was performed in an external European laboratory. Despite these promising results, LG Chem announced in May 2023 that it does not intend to continue the MASH programme. The programme therefore reverts to Sprint Bioscience, with no financial obligations to LG Chem. Sprint Bioscience is now working to find a new partner for the programme.
**The terms MASLD and MASH have replaced NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis). Although the names have changed, the diseases are the same.