For the first time in over 70 years, a new testosterone replacement therapy has been unveiled. Dr Vassilios Papadopoulos and Dr Costas Karatzas, co-founders of Acesis BioMed, explain how their ‘first-in-class’ peptide therapeutics could transform men’s health across the world.
Low testosterone is a widespread clinical problem that affects up to 40% of the world’s male population and is linked to obesity, high blood pressure, infertility and other serious health issues. High prevalence of hypogonadism (~ 40%) has been reported in patients with Type 2 Diabetes. New research has also found that men with low testosterone are more likely to die from COVID-19.
Acesis is developing first-in-class non-steroidal oral peptide therapeutics which will induce endogenous testosterone production in testosterone-deficient males. Put simply, they are developing therapies that instruct the body’s own cells to produce testosterone naturally.
All current Testosterone Replacement Therapy (TRT) treatments on the market are exogenous and based on old steroid technology developed in the 1930s. In 2015, potential side effects were flagged up about to their use, including stroke, heart attack, infertility and specific prostate cancer risk.
Acesis BioMed believes its product candidates will have a superior safety profile as the body is using its own cells to produce testosterone naturally.
Acesis Biomed’s science and pipeline product candidates are based on the 30 years of research of Dr Vassilios Papadopoulos, a leading authority in the field of steroidogenesis. Co-founder, Director and Chairman of the Scientific Advisory Board at Acesis, Dr Papadopoulos discovered that a protein (14-3-3ε) acts as a negative regulator of steroidogenesis by forming a scaffold with the outer mitochondrial membrane voltage-dependent anion channel (VDAC1) protein that limits the availability of cholesterol for steroidogenesis.
In 2014/15 Dr Papadopoulos’s team discovered peptides which blocked the 14-3-3ε-VDAC1 interactions while at the same time increased VDAC1-translocator protein interactions that induced steroid formation in rat testes, leading to increased serum T levels.
This platform technology and novel method of inducing steroidogenesis occurred during his time as professor at McGill University, and as executive director at the Research Institute of the McGill University Health Centre, Montreal, where Dr Papadopoulos and Acesis’ current CEO, Dr Costas Karatzas, met. Acesis Biomed was founded shortly after this discovery to advance it through the appropriate drug development program, which involved identification of the lead peptide and extensive in-vitro and in-vivo testing. Our current stage of development is to perform pre-IND and IND-enabling studies with our orally bioavailable tetrapeptide which is demonstrated to be inducing T production in the relevant models.
Why is your peptide product candidate considered “first in class”?
VP: A first-in-class medication is a pharmaceutical that uses a “new and unique mechanism of action” to treat a particular medical condition and is an indicator of the innovative nature of a drug. Our peptide-based product candidate is designed to have a mechanism of action (targeting the 14-3-3ε-VDAC1 protein to protein interaction complex) which is different from those of existing testosterone therapies.
Low testosterone is a major medical problem with a growing demand for effective treatments, so why have there been no similar breakthroughs in over 70 years?
VP: In recent decades, the number of hypogonadal men with low testosterone has grown at a significant rate also due to the increase in the global average age. All existing treatments are exogenous in nature and based on a steroidal chemistry core initially developed in the 1930’s.
As a result, there has been an increasingly growing demand for the development of novel, safer and more effective treatments, a demand which has promoted new research into the field. Acesis is well positioned to service this demand with its peptide-based platform.
Our novel peptide-based product candidates are moving away from this antiquated steroid based chemical core, enabling the “recovery” of T production by the testes rather than replacing endogenous T resulting to supraphysiological levels and side effects.
Congratulations on identifying your lead peptide. Could you explain how treatments based on this product candidate will work and what indications you will be targeting?
CK: Our mission at Acesis is to revolutionise the treatment of male hypogonadism, as well as a variety of other linked co-morbidities and prevalent diseases. Acesis Biomed is looking forward to advancing its core program for the treatment of male hypogonadism and to pursuing partnerships and out-licensing opportunities with significant players in the pharmaceutical and biotechnology industries for the other co-morbidities of T deficiency. Some of these players may have lost market share due to the FDA Black-box warning for their T pipeline and may be seeking safer alternatives to treat hypogonadism or related co-morbidities.
The Company currently owns two patent families which relate to peptide-based compounds, as well as their use for modulating endogenous steroidogenesis. We are in the process to transition our orally bioavailable lead ACE-167 peptide through pre-IND and IND-enabling studies prior to requesting the authorization of regulatory bodies to initiate clinical studies. The first indication which we are planning to transition into the clinic is male hypogonadism.
We are keen to progress our product candidate platform for a number of additional chronic disease indications where there is a strong, scientific evidence linking them to low testosterone. Many of these indications affect a significant proportion of the global population, including metabolic syndrome, non-alcoholic fatty liver disease, prediabetes, type 2 diabetes, osteoporosis and obesity.
Another condition of interest includes the Klinefelter syndrome, a chromosomal condition in boys and men that produce a reduced amount of testosterone. There is quite a range of reports indicating for example that opioid medications suppress testosterone levels, that sleep deprivation lowers testosterone but at the same time low T may contribute to insomnia, and it is notable that head trauma or concussions are a common reason for low T in younger men.
What will be the main benefits of your therapeutics?
CK: When compared to existing testosterone therapies on the market, Acesis Biomed’s product candidate is expected to have a significantly improved safety profile and be more effective. Our drug candidates will undergo extensive clinical testing and regulatory evaluation and designed with a novel mechanism of action (MoA)are positioned as a major innovation in the space in over 70 years. Testosterone Replacement Therapy (‘TRT’) methods are currently available in the market are exogenous and include: T-gels (eg. AndroGel, Testim® and Fortesta); oral (methyl-T, Jatenzo); buccal patches; implanted subcutaneous pellets (Testopel), long-acting T-injectable (Aveed), sub-cutaneous weekly auto-injector (Xyosted); transdermal patches (Androderm) and intranasal (Natesto). However, these treatments carry significant risks as reported by the FDA in 2014 and 2015 when a “black box warning” label was issued on these existing marketed T treatments.
Is there any evidence that low testosterone impacts Covid-19 infections, and if so, could TRT aid treatment?
VP: Testosterone replacement therapy has positive impact in men’s well-being, but if low testosterone is treated in a safer way under the direction of a qualified physician, it can help counter the signs and symptoms even earlier and more efficiently. With evidence that our testosterone recovery therapy could also target significant indications linked to low testosterone, including the likes of type II diabetes, the potential beneficial implications are extremely promising. Research into Covid-19, and the direct mechanisms which connect it with low testosterone, is still new and relatively ambiguous. According to National Geographic, for example, there is now a wealth of data that shows getting infected with Covid-19 can cause erectile dysfunction and other reproductive health problems for men.
Is there anything else you would like to add, for example, future exciting developments?
CK: Testosterone Replacement Therapy represents a global market opportunity of $2-3 billion dollars. U.S. represents the vast majority of global sales at ~ $1.3 billion, with injectable formulations representing ~ 35% and gels ~ 60% of the dollar sales in 2020. Since the market is suffering from a lack of introduction of innovative products, it is believed that the testosterone replacement therapy market is likely to hit a patent cliff in the next 6 to 8 years. All TRT products are based on very old T core chemistry-based derivatives and formulations for T delivery. The expiration of these patents would have an impact on firms’ TRT product revenues. As such, we are really excited at the possibility to progress the development of our lead candidate and take centre stage in what is becoming such an important and swiftly expanding market where T deficiency plays a major role.
WhileFull details about the therapeutics can be found at acesisbio.com.