Biotech company publishes new positive preclinical data to better understand endometriosis and inflammatory disorders

The biotech company Mithra has announced new positive data from preclinical studies on inhibitors of CSF-1R in development for the treatment of endometriosis, oncology and inflammatory disorders.

Colony-stimulating factor 1 receptor (CSF-1R) is a cell-surface tyrosine kinase receptor and a key regulator of macrophage biology and homeostasis.

Tumour-associated macrophages are key components of the tumour microenvironment and have emerged as a promising avenue for discovery of novel cancer immunotherapies. CSF-1R kinase inhibition is therefore a promising therapeutic strategy for cancer treatment.

“We are encouraged that the lead CSF-1R inhibitor demonstrated efficacy as a single agent in three different preclinical cancer models and that the data suggest it may be synergistic when used in combination with PD-1 inhibitors,” said Graham Dixon, chief scientific officer of Mithra.

“This provides a strong rationale supporting further development of CSF-1R inhibitors in combination with immune checkpoint inhibitors.

“We look forward to further evaluating and advancing these promising small molecule therapeutic candidates.”

According to Mithra, a first study, conducted in a widely used preclinical immune-oncology model, demonstrated that the lead compound, as well as several back-ups, showed anti-tumour activity as a single agent.

The well tolerated compounds demonstrated pronounced and consistent modulation of the tumour microenvironment, including an increase of T cells, which mediate anti-tumour immune responses, and infiltration of natural killer (NK) cells, containing enzymes that can kill tumour cells, into the tumours.

Data showed a decrease in tumour-infiltrating macrophages, a type of white blood cell that plays an important role in the human immune system, and repolarisation of the tumour-supportive M2 macrophage to the tumour-suppressive M1 macrophage. These results are consistent with anti-tumour activity, and tumour growth inhibition of up to 59 per cent.

The efficacy of the lead compound was further assessed as a single agent or in combination with anti PD1 therapeutic antibody in additional preclinical studies using three different cancer models: MC38 (colorectal), 4T1 (orthotopic triple negative breast) and EMT6 (triple negative breast).

The significant anti-tumour activity of the lead compound used as a single agent was confirmed and was further enhanced with twice daily administration, compared to once daily.

Additivity or synergy on tumour growth inhibition was observed when the lead compound was used in combination with anti-PD1 therapy; the triple negative breast cancer model showed that 50 per cent of the animals achieved a complete tumour regression after the combination treatment. Further data will be presented in a peer-reviewed setting.

The research was conducted under a partnership with BCI Pharma, first announced in November 2021.

Mithra’s primary focus is on endometriosis and cancers affecting women, including orphan indications such as triple negative breast cancer (TNBC).