Article in BioStock: Follicum shows rapid progress with diabetes drug candidate

BioStock published an article about Follicum’s diabetes project on 7 January 2019 in Swedish. The article is here translated into English.

Follicum is currently running its flagship drug candidate for hair loss, FOL-005, through Phase II clinical trials and the company has recently received key patent extension in the United States as well as an “intention to grant” in Europe. At the same time, the company’s new diabetes treatment project is rapidly advancing in preclinical development. A drug candidate will be selected in early 2019 and is expected to reach clinical Phase I studies by 2020.

Diabetes: A global health crisis
Diabetes is a chronic disease that affects more than 500 million people worldwide. Globally, the diabetes prevalence among adults has more than doubled since 1980, from 4.3 percent to 9.0 percent in 2014. The prevalence was lowest in North Western Europe (about 5 percent) and highest in Polynesia and Micronesia (almost 25 percent). The situation is not expected to improve in the near future, which means that the economic burden for society continues to mount at an alarming rate.

Different types of diabetes
In type 2 diabetes, the ability to produce insulin is not completely abolished, but the amount of insulin is insufficient for the body’s needs. The body is not only unable to respond with increased insulin production when blood sugar rises after, for example, a meal, the ability of the tissues to utilize the insulin is also reduced. Hence, more than normal amounts of insulin are needed to control blood sugar. Obesity is one of the underlying factors behind the body’s loss of sensitivity to insulin.

Obese individuals who have not contracted type 2 diabetes are able to produce sufficient amounts of insulin, up to five to ten times the normal, to keep blood sugar levels within normal levels despite the reduced sensitivity to insulin in the cells of the body. A sedentary life style, i.e. low levels of physical activity, leads to a further deterioration of the effect of insulin.

In type 1 diabetes, the body’s failure to control blood sugar is due to an inability of the pancreas to produce insulin caused by an autoimmune response resulting in killing of the beta cells in the pancreas. These cells are crucial for the production of insulin, the hormone that regulates blood sugar levels in the body. Consequently, insulin must be administered to such patients throughout their lives.

An expensive, widespread disease
Diabetes-related healthcare costs were estimated to amount to USD 850 billion in 2017. A large proportion of the costs derive from serious complications such as myocardial infarction, stroke, nerve damage or kidney disease caused by the underlying inability of the diabetes patient to utilize sugar (glucose) from the blood and use it as energy for the surrounding cells in the body.

The fight against blood sugar peaks
Medicines that help improve the body’s ability to lower blood sugar levels are already on the market. Examples include metformin, DPP-4 inhibitors, SGL-2 inhibitors and GLP-1 receptor agonists. These treatments are relatively effective at an early stage of type 2 diabetes, but with an aggravated disease, insulin is required.

The major challenge for diabetics is to keep blood sugar levels at an even level. Fluctuating blood glucose levels have a very negative effect on the body’s cells and are a strong contributing factor to diabetes-related sequelae such as cardiovascular disease, kidney complications, liver fatigue, cancer and diabetic leg ulcers. Diabetes-related complications result in severe personal suffering for the individual patient and also increasing costs for society.

Follicum’s goal is to develop drugs that improve the conditions for controlling blood glucose levels in combination with specifically preventing certain diabetic complications.

Follicum’s new peptide class shows promising preclinical results
Follicum is a biotech company based in Lund, primarily known for developing FOL-005, a drug against hair loss. In addition, the company is currently undertaking preclinical studies with a new peptide class, FOL-014 that it hopes will help delay, or even prevent, complications related to diabetes.

The FOL-014 class, a spin-off of the FOL-005 project, has so far produced promising data. In vitro studies have shown that several peptides bind to the beta cells and protect their ability to secrete insulin when exposed to high levels of glucose for a long time (see figure), a simulation of the physiological situation in diabetic patients.

Potential for better treatment outcomes compared to established alternatives
In most cases, Follicum’s peptides exerted a better effect than GLP-1, an efficient, endogenous substance upon which a number of successful drugs have been based. Furthermore, in vitro studies have shown that Follicum’s peptides have the ability to increase insulin levels in response to increasing blood glucose concentrations.

In in vivo models, the peptides have also shown good responses, e.g. to lower blood glucose levels after glucose loading tests. In Type 1 diabetes, the peptides have also shown a very exciting result, namely that they delay the onset of diabetes in an in vivo model. Several in vivo studies are currently ongoing.

Experiments with insulin-producing beta cells show that Follicum's peptides retain the ability to secrete insulin following prolonged exposure to high levels of glucose. The study mimics the physiological situation in diabetic patients, where chronic high glucose levels impair insulin secretion. The white bar represents healthy cells and the dark blue bar represents diabetic cells. The light blue bars represent data showing that treatment of diabetic cells with Follicum's different peptides (bars 1-10) restores the ability of the cells to secrete insulin. The stars (*) on the bars indicate a statistically significant difference to the control (high glucose).

Follicum expands its patent portfolio
The positive results have led to an expansion and broadening of Follicum’s patent portfolio, a new patent application was filed November 12, 2018. The new patent application followed immediately after the publication of the company’s first diabetic patent and will further strengthen Follicum’s role in diabetes.

Good relations with diabetes giants
The company has also expanded its network significantly by entering into a comprehensive diabetes project together with leading pharmaceutical companies such as Novo Nordisk, Pfizer, Johnson & Johnson, Probi, Cardiovax and Region Skåne. The project is funded by a SEK 100 million grant from the Foundation for Strategic Research.

Moreover, Follicum’s research group at Lund University has, for the second time, received funding (DKK 1 000 000) from the Novo Nordisk Foundation; funds that are directly used for the company’s research.

Funding of a post-doc position
On behalf of the diabetes network, Follicum has applied for, and following an evaluation by a group of international advisors, been assigned additional resources in the form of a so-called postdoctoral position. The duration of the position is 2 years and it is fully funded by the diabetes network.

The postdoctoral work will mainly focus on further investigating the molecular mechanisms with which the peptides act to regulate blood glucose levels and how they function to reduce diabetes-related complications. The work will significantly accelerate the development of Follicum’s diabetes project and build further, solid value. An international recruitment process to find the right candidate will be completed during the first quarter of 2019 and the project is expected to run through 2021.

Follicum sees great potential in its moleclues
Follicum has great hopes for its molecules, and with good reason. Although hair loss and diabetes are two widely different indications, there is a biological link between the diseases. Research has shown that men can suffer from hair loss already in early stages of diabetes and that hair loss can even constitute an early sign of type 2 diabetes. Lack of insulin seems to have a negative effect on the transition of the hair follicles to an active growth phase, which may make the hair grow slower or not at all in diabetics.

The hair growth process is reminiscent of tissue repair and many diabetic complications occur due to reduced ability to repair damaged tissue. An improved ability to repair a damaged tissue – e.g. damaged blood vessels that are very common in diabetic patients – will reduce the severity of diabetic complications.

Anna Hultgårdh, one of Follicum’s founders, believes that if the results from subsequent studies are positive, it indicates that treatment with these peptide classes can lead to fewer cases of myocardial infarction and stroke in diabetic patients in the future. Read more (in Swedish).

Aiming for deal following clinical studies
The company’s business strategy is to out-license or sell its pharmaceutical projects to pharmaceutical companies and / or financial investors after completed clinical studies. For the diabetes project there is a large range of potential, global stakeholders. Several of the major pharmaceutical companies have their own diabetes portfolios and are constantly in search of new, innovative candidates to establish or maintain a prominent position within the field in question.

Regarding the diabetes project, Follicum plans to select a drug candidate for further preclinical development at the beginning of 2019 and initiate clinical trials in 2020. Thus, the company will take its pipeline rapidly forward and maintain its positive vision of the future.

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