Approach to stimulate testosterone production instead of synthesis on the horizon

Acesis Biomed’s lead candidate has the potential to provide a safer solution for treating low testosterone and hypogonadism compared to existing treatments by requiring the body’s own cells to naturally produce testosterone. Image source: Shutterstock

Low testosterone in men is a widespread clinical problem with obesity, high blood pressure, and type 2 diabetes. Almost 39 percent of the global male population aged 45 and over suffers from hypogonadism. But, despite this, there is a serious lack of innovation in the field, with all current therapies available being based on synthetic testosterone developed in the 1930s.

Hypogonadism is widely referred to as male menopause because it primarily begins to affect men in their forties, affecting their mood, energy, fertility and can lead to osteoporosis. However, low testosterone and hypogonadism can also affect younger men.

“After the age of 30, testosterone levels decrease by an average of 1 to 2% per year, depending on ethnicity and several other conditions or co-morbidities,” says CEO and co-founder of Acesis Biomed, Dr Costas Karatzas in an interview with Pharmaceutical technology.

The company is unique in its approach to treating low testosterone, “without being a testosterone company” and is developing a first-class non-steroidal oral peptide therapy designed to induce endogenous testosterone production in testosterone deficient men .

Currently in preclinical development, Acesis ACE-167 lead candidate has the potential to provide a safer solution for treating low testosterone and hypogonadism compared to existing treatments by instructing the body’s own cells to naturally produce blood. testosterone. This will contrast with AKA synthetic testosterone testosterone replacement therapy (TRT) or anabolic steroids which can have serious side effects and high potential for abuse as performance enhancing drugs.

“Many symptoms associated with low testosterone have been lumped together under a depressive disorder. So, many people with hypogonadism are given antidepressants, which makes some problems worse – their sex drive never returns and their ability to function is even worse.

In March 2019, the FDA approved the TRT capsule from Clarus Therapeutics to treat men with certain forms of hypogonadism. It was the first and only oral soft gel approved by the FDA for TRT, but as Karatzas says, it “is still based on chemistry that is 70 years old.” As with other TRTs on the market, it is also only indicated for the 40-65 age group, thus excluding younger and older men. For those 65 and over, the agency postulates that the process of lowering testosterone is part of normal aging.

A New Testosterone Therapy Paradigm on the Horizon?

Acesis Biomed’s main candidate, ACE-167, is an oral non-steroidal treatment that asks the testis to produce its own testosterone. The testosterone (T) peptide modulator is developed under the expertise of Dr. Vassilios Papadopoulous, dean of the School of Pharmacy at the University of Southern California and co-founder of Acesis. He has received millions of dollars in funding from multiple sources to support research that has led to the understanding of the mechanism underlying steroidogenesis, its regulation, and the identification of a new molecular therapeutic target for T restoration.

Karatzas says that since the company’s asset is not a steroid like testosterone, it does not have the side effects seen with widely used TRTs, including enlarged breasts, high blood pressure, breast problems. bone growth and acne. “It is a peptide which, when taken orally, is designed to instruct the testes to produce testosterone at normal physiological levels.”

“The transport of cholesterol to the mitochondrial membrane is the limiting factor in the amount of steroids produced by the testes,” explains Karatzas. There is a protein complex that affects the way cholesterol is transported in the mitochondria, and Dr. Papadopoulos has discovered a negative regulator of these cholesterol-transporting proteins, he explains. The company’s intellectual property relates to “peptides which can eliminate this negative regulator and allow cholesterol to move through the mitochondria to control the maximum amount of steroids produced.”

The TRTs currently on the market involve the delivery of testosterone to the body via a gel, injection, patch, or as mentioned more recently, a pill.

Their administration can be almost as problematic as the TRTs themselves. Injections may require patients to see their doctor every two weeks or six months. In the weeks leading up to the next stroke, men may suffer from the effects of lowered testosterone levels. In addition, they run the risk of being addictive and abused, which requires close monitoring of recipients.

Over the past few years, there has been a huge increase in the off-label use, abuse and abuse of testosterone which is often presented to men for the improvement of things related to facets. desirable aspects of male masculinity – energy, hair growth, sexual performance and muscle gains.

Steroids, differentiated only from TRT by being illegal, without medical supervision, and usually given in much higher doses, were popularized by bodybuilders in the ’80s and’ 90s. They quickly became attractive to young men who wanted drugs. more muscular physique.

When abused or taken in large doses, not only can it become very addicting, but it can also stop the organic production of testosterone in the body, leading to reduction in testicular size and infertility. It is also accompanied by an increased risk of blood clots and heart attack and can lead to paranoia and aggression.

Patches and gels, on the other hand, can cause cross-contamination of partners and children. Oral treatment that encourages the body to make its own testosterone could be a game-changer. Karatzas says ACE-167 is not conducive to abuse or cross-contamination due to this unique protein-to-protein interaction.

There are nine therapies for the treatment of low testosterone and hypogonadism in preclinical development or in Phase I trials, including Acesis, but the company is the only one developing an oral treatment that encourages the production of testosterone by the body rather than administering a synthetic hormone.

“Based on our preclinical data to date, there is no excessive increase in testosterone. The limit on the amount of testosterone you produce is personalized and depends on your own machine.

A myriad of risk factors = huge market value

Karatzas says that experts and pharmaceutical companies have only recently realized the central role that testosterone plays as a protagonist in many co-morbidities. Aside from hypogonadism, it has been shown in recent years that low levels of testosterone in the blood are also an independent predictor of a number of cardiovascular risk factors. This includes the metabolic syndromes in general – obesity, abnormal cholesterol levels, high blood pressure, and hypertension – all of which can lead to type 2 diabetes and heart disease.

“The prevalence of hypogonadism appears to be close to 50% in people with type 2 diabetes and obesity. In terms of development space for hypogonadism, Karatzas says the market is between $ 3-4 billion per year for the FDA-approved indication in the 40-65 age group. But, there will be more demand if regulators allow use outside this age threshold, and there is potential for other comorbidities as well, he adds.

Acesis’ current clinical development plan is to demonstrate the safety and early efficacy of ACE-167 in people with hypogonadism in this age group of 40 to 65 years, where there is already a approval route. A phase I trial is expected to begin within the next two years.

After that, Acesis will evaluate the peptide in a number of secondary markets, including obesity, prediabetes, type 2 diabetes, and reversible non-alcoholic fatty liver disease (NAFLD). The company also plans to collaborate with foundations for patients with Klinefelter syndrome, a condition in which an extra X chromosome is present in addition to the XY, resulting in low testosterone. Boys with Kleinfelter are put on TRT but they often face the problem of infertility, and Acesis’ approach can help promote sexual maturity.

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Shawn Beecher

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