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

The research was conducted under a partnership with BCI Pharma

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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).

Pregnancy

Climbing during pregnancy may be safer than long assumed, study finds

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Climbing during the third trimester was not linked to higher rates of self-reported pregnancy complications in a global study.

The findings provide direct evidence on an activity pregnant women have traditionally been advised to avoid because of concerns about falls.

Researchers surveyed 692 people about climbing during pregnancy, falls, maternal and baby health outcomes and their return to the activity after giving birth.

The study recorded almost 64,000 hours of climbing among participants.

During that time, participants reported 155 “hard falls”, defined as falls or catches forceful enough to be remembered or cause concern.

The rate of adverse clinical events, meaning negative medical outcomes affecting the pregnancy or baby, was 0.03 per 1,000 hours of climbing exposure. All babies in the study were born live.

Researchers found no significant difference in pregnancy or foetal health outcomes between participants who stopped climbing at or before 27 weeks and those who continued beyond that point.

The findings suggest continuing the activity into the third trimester was not associated with increased self-reported complications among those surveyed.

The survey also found 96 per cent of participants said that, despite concerns about climbing while pregnant, they felt “happy” or “very happy” that they had continued.

Margie Davenport, professor in the Faculty of Kinesiology, Sport, and Recreation and lead author of the study, said the preliminary findings challenge an assumption about maternal exercise that had been based on opinion rather than research.

She said: “For decades we have restricted pregnant women from activities like climbing due to concern for their health and the health of the baby, but our evidence suggests it’s beneficial for both mental and physical health.”

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Entrepreneur

Peripear wins Innovate UK Women in Innovation Award

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Medtech startup Peripear has won an Innovate UK award for developing a wearable designed to prevent perineal trauma during childbirth.

The Oxford-based company is developing a hands-free warm compress device for use on the perineum during the second stage of labour.

 

Peripear describes its product as the world’s first automated perineal thermotherapy wearable, designed to prevent perineal trauma during childbirth.

The device is intended to reduce severe tearing and episiotomies while improving maternal comfort.

Peripear has secured an Innovate UK Women in Innovation Award and a £74,974 grant.

The funding will support further product development ahead of the company’s planned first-in-human study.

Nina van Schaick, co-founder and chief operating officer of Peripear and midwife, said: “I’m sure I wasn’t the only one to see this gap.

“I was incredibly lucky to meet my co-founder, Eviatar Natan, right as my frustration about the lack of translation of evidence into practice had peaked.

“There was a proven mechanism that could reduce injuries occurring in up to 90 per cent of vaginal births, and it was being left out of clinical pathways simply because no standardised tool existed to deliver it.

 “I’m a farmer’s granddaughter, and when I started practising over 14 years ago, I asked: where is the tool I need to implement this evidence? I looked around and realised we were still asking clinicians to improvise.

“Peripear is what happens when the person who has lived the problem, both personally and professionally, meets the person who can help her build the solution.”

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Hormonal health

Coffee linked to healthier body composition and distinct sex hormone changes – study

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Higher coffee consumption has been linked to lower body fat, greater muscle mass and differing sex hormone patterns in men and women in a Finnish study.

Researchers found people who drank more coffee had lower levels of total and visceral fat, the fat stored around internal organs, as well as greater skeletal muscle mass.

These associations were seen even though participants had a similar body mass index (BMI), a measure of weight relative to height.

The University of Oulu study analysed data from 2,264 people aged 46 who were part of the Northern Finland Birth Cohort 1966, looking at habitual consumption alongside circulating metabolites, cardiometabolic risk markers and sex hormones.

In both men and women, higher consumption was correlated with lower circulating levels of branched-chain amino acids.

Persistently high levels of these molecules have previously been linked to insulin resistance, when the body responds less effectively to insulin, and a higher risk of type 2 diabetes.

The strongest differences between the sexes were seen in men. Higher consumption was linked to a more favourable glucose and insulin profile, higher total and bioavailable testosterone and increased levels of sex hormone-binding globulin (SHBG).

SHBG is a protein that carries sex hormones such as testosterone through the bloodstream and influences how much hormone is available for the body to use.

At the same time, free testosterone and the free androgen index were modestly lower in men.

Among women, hormone associations were more limited, mainly involving higher SHBG and lower measures of free androgens, a group of hormones that includes testosterone.

Luca Verroest, lead author of the study and doctoral researcher at the University of Oulu, said: “Coffee is consumed by millions of people every day, yet we still know surprisingly little about how it relates to our metabolism and hormones.

“What stood out in our findings was a distinct hormonal signature that didn’t disappear even after we took into account BMI and lifestyle factors, with several of these associations differing between men and women.”

The researchers said hormonal pathways could partly explain the relationship between consumption and metabolic health.

However, the research was observational, meaning it can identify associations but cannot establish that drinking coffee caused the biological differences seen among participants.

The study is particularly relevant in Finland, one of the world’s highest coffee-consuming countries, where annual consumption averages around 11.8 kilograms per person.

Researchers are now investigating whether coffee itself drives the biological changes and which compounds could be responsible, initially using animal models.

The longer-term aim is to move to human intervention studies, although the researchers said further research would be needed before the findings could be used to inform dietary recommendations.

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