Her company is developing a new tablet form obesity drug
Av Pila Pharma is built on discoveries made by Dorte X Gram as a PhD student at Novo Nordisk at the turn of the millennium. Her assignment was to develop a method for measuring insulin resistance, and she then tested capsaicin, the substance causing the perceived heat of the chilli fruit.
At the time, the so-called chilli receptor was known to play a role in pain perception and the regulation of inflammation - a discovery that would later earn David Julius the Nobel Prize in Physiology or Medicine.
However, in animal studies, Dorte X Gram found that it also impacted metabolism. She ended up filing a patent application on the mechanism, i.e. blocking of the chilli receptor as a way to treat obesity and obesity-related diseases, particularly diabetes.
“As a result, I got a PhD, got hired by Novo Nordisk, and then I was in the business of diabetes and obesity research.”
At the Danish pharmaceutical giant, she joined a completely different project involving second-generation GLP1 analogues. Her team was researching ways to stabilise the hormone to slow its degradation.
“I would guess we checked about 400 substances, and in that haystack, we found a few that could lower blood sugar for a longer period of time. One of them was number 217, and I was actually the first member of the project to discover that this analogue was exceptional and had all the positive characteristics we were looking for.”
According to Dorte X Gram, this turned out to be the substance that would later become semaglutide, the active ingredient in the future blockbusters Ozempic and Wegovy.
At this point, she suffered a personal bereavement and spent some time away from Novo Nordisk. On her return, her work in the research unit had taken a turn she did not like. This led her to move to another department and eventually chose to leave Novo Nordisk, but prior to that, she had bought out her patent on the chilli receptor.
In 2014, Pila Pharma was founded to further the project. Two years later, the company bought a molecule, XEN-D0501, a so-called TRPV1 antagonist targeting the chilli receptor.
“My patent was about obesity and obesity-related diseases, so I always knew that was the centrepiece. However, when I founded Pila Pharma, obesity was not considered a disease, so I had to target diabetes first.”
To date, the company has conducted two phase IIa studies, which indicated that the treatment was well tolerated by type 2 diabetes patients and enhanced insulin response. Furthermore, a statistically significant effect was found for a biomarker of heart failure.
A phase IIa study is now being prepared, aiming to identify the maximum tolerated dose of XEN-D0501 in obese people with type 2 diabetes and to evaluate the safety profile after three months of chronic treatment. The study will also include sufficient participants to enable efficacy readouts in body weight reduction.
Recently, the company raised SEK 10 million in a private placement to fund the study.
“With so much focus on obesity, we’ve been talking more about it. We don’t have the relevant data yet, but I am very optimistic about the effect of our molecule not only on blood sugar and insulin but also on regulating body weight when we start chronic dosing,” says Dorte X Gram.
She is convinced that the drug candidate could potentially have the same beneficial effects as the GLP1 analogues for obesity but without the side effects of nausea and vomiting.
“However, since the receptor we are targeting is located on pain-sensitive nerves, numbing and pain-relieving effects are plausible. This could be an added benefit, provided we can find a level at which it does not constitute a problem but a benefit for those in pain.”
As for herself, she handed over the CEO position to her son Gustav Gram this spring but continues to work as CSO and Chair of the Board, although it doesn’t make much difference, she says.
“It’s business as usual. The main difference is that Gustav is more interested in the investment part than I am, while I am more focused on the scientific part, so we have divided up the tasks more.”
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