Type 2 diabetes is one of the world’s most common diseases. A company that wants a piece of the diabetes market pie is Malmö-based Pila Pharma, which is currently conducting preclinical studies with its candidate XEN-D0501. BioStock has taken a closer look at the clinical concept that underpins Pila Pharma’s development.
Diabetes is a collection of diseases where the common denominator high levels of blood sugar, i.e., glucose concentration in the blood exceeds desirable levels. Glucose plays a vital role in the functioning of the body and is used to form the energy that cells need to function properly. The body uses the hormones insulin and glucagon to regulate the uptake and secretion of glucose, and it is when this regulation does not work that diabetes occurs.
Today’s treatments focus on insulin
In the most common form of diabetes – type 2 – the body can no longer produce enough insulin for the cells to absorb glucose properly, or the cells’ insulin sensitivity has deteriorated. It is these two aspects of the disease that today’s treatments focus on – to help the body produce insulin or increase the cells’ insulin sensitivity.
The market for the treatment of diabetes was estimated to be worth just under USD 70 billion in 2019 and continued growth is expected, driven by increased obesity and a sedentary lifestyle.
A changing treatment landscape
In addition to a healthy diet and exercise, first-line treatment today consists of metformin, which works by both increasing the cells’ insulin sensitivity and reducing the liver’s own sugar production. In some patients, however, the effect of metformin decreases over time, which means that they need to move on to other treatment options.
For patients with advanced disease, the addition of insulin has long been the standard procedure, but in recent years it has become increasingly common with treatments that instead help the body’s own insulin production. A good example is the emergence of GLP1 analogues, which, among other things, increases the pancreas’ production of insulin.
Targeting the chili receptor
There are of course numerous players on the diabetes market, and one company that wants to break in among the competition is Malmö-based Pila Pharma. With its treatment concept, the company hopes to affect both insulin production and the insulin sensitivity of cells. Founder and CEO Dorte X Gram has attacked the problem via the so-called “chili receptor,” TRPV1, whose main function is to react to injuries, for example by sending pain signals and boost local inflammation.
The discovery of the TRPV1 receptor at the end the 1990s represented a significant breakthrough leading to the identification of more receptors in the body – a scientific advancement that was awarded the Nobel Prize in Medicine in 2021.
TRPV1 also plays a role in diabetes
Gram believes that TRPV1, in addition to its main role as a mediator of sensations, also plays a role in diabetes. Her hypothesis is that a fat tissue that is too fat causes the TRPV1 receptors to be more stimulated than usual. This leads to a persistent low-intensity inflammatory response, which in turn inhibits insulin production and insulin sensitivity. She believes that this can lead to a vicious spiral where the body tries to compensate by producing more insulin, which in turn further adds to the abnormal inflammatory response.
According to Gram, prolonged overstimulation can also mean that the receptors eventually wear out, which can lead to nerve damage, chronic pain and chronic foot ulcers.
Aiming to inhibit TRPV1
Inhibiting the TRPV receptor should then make it possible to avoid the persistent inflammatory response and stimulate both insulin production and insulin sensitivity. This is exactly what Pila Pharma’s drug candidate XEN-DO501 is supposed to do.
There is evidence supporting this hypothesis. The company have seen a correlation between inhibited TRPV1 and increased insulin production and increased insulin sensitivity in animal models, where e.g., mice whose TRPV1 was knocked out and that were given a high-fat diet did not develop any glucose intolerance and at the same time showed an improved insulin secretion.
In addition, Pila Pharma has also received preliminary efficacy results in humans. In a phase IIa study, diabetic patients were given tablets of 4 mg XEN-D0501 (one in the morning and one in the evening?) for 28 days. After the treatment cycle, they showed a significantly higher insulin level compared to a group of patients who received placebo after an “oral glucose load” or during a so-called “oral glucose tolerance test.”
Phase IIb is the next milestone
The next major step in the development is to confirm the preliminary efficacy results in humans. Preparations are in full swing, with the start of a longer preclinical study of 13 weeks being the next milestone, which you can read more about here. If everything goes as it should, the company is expected to be able to enter phase IIb sometime next year, where the hope is to obtain further evidence that it is on the right track.The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.