Turin based Resalis Therapeutics has successfully acquired seed funding to support the development of treatments for certain metabolic diseases. Award winning Eva Castagnetti, CEO, describes the innovative work her organisation undertakes and discusses secrets of success.

Metabolic disorders occur when abnormal chemical reactions in the body disrupt the process of breaking foods down into fuel for healthy living. As a result, certain organs do not function correctly, leading to diseases such as Metabolic Fatty Acid Liver Disorder (MAFLD). A progressive form of MAFLD where inflammation and storage of fat within the liver can cause cirrhosis is known as Non-Alcoholic Steatohepatitis (NASH).

Patients with advanced stages of NASH are susceptible to serious complications, including liver failure and cancer. In addition, sufferers of MAFLD and NASH are likely to have a high risk of developing cardiovascular problems. Yet despite MAFLD being one of the most common types of liver disease – currently known to affect up to 25 to 30 per cent of the population of the US – diagnosis can remain undetected due to a lack of apparent symptoms. Of greater concern, apart from general weight loss advice or lifestyle changes which are in many cases difficult to implement, is the fact that there are currently no approved medications on the market designed specifically for the treatment of MAFLD / NASH. 

With a deep passion, vast expertise in the drug development process and a proven track record in dealing with suppliers, regulatory authorities and pharmaceutical partners, Eva Castagnetti, Founder and CEO of Resalis Therapeutics, has successfully been awarded significant seed capital to advance the development of treatments for certain metabolic disorders. 

Here, Eva talks to us about the importance of being able to treat metabolic disorders effectively, the science behind Resalis Therapeutic’s ambitious research and shares her ethos and personal insight on success in previously unchartered waters.

We’ve briefly touched on conditions known as MAFLD and NASH, are there any other metabolic disorders for which treatments are currently limited?

Two main diseases affecting the populations of today are obesity and metastatic breast cancer, both of which are often associated with a metabolic disorder. 

Obesity can, of course, be caused by genetic factors, or personal diet and lifestyle choices, but it is a severe medical problem which increases the likelihood of other conditions such as cardiovascular disorders, diabetes, high blood pressures and certain cancers.

Metastatic breast cancer, or Stage 4 breast cancer, refers to cancer which has spread beyond the breast tissue and lymph nodes into other areas of the body such as the liver, brain, bones, etc. Treatments are limited and currently there is no real cure. However, the role of metabolism in the progression of breast cancer is something which is gradually being emphasised and understanding the mechanisms behind this will provide important clues to help develop therapeutic approaches for treatment.

Resalis Therapeutics has carried out some pioneering medical techniques in this area. Could you tell us more about your organisation and the science behind its potential breakthrough in treating metabolic disorders? 

We’re a biopharma company based in Italy, focusing on developing therapies to treat metabolic conditions such as MAFLD / NASH / obesity as well as cancer by targeting and inhibiting a class of molecules called microRNAs. Our team comprises specialist scientific knowledge and expertise surrounding RNA-based drug design, as well as molecular biology and genetic and progression of advanced tumours. We also have an important overview of the drug development process, interaction with regulatory authorities, investors and pharma partners.     

At the moment we’re working on applying microRNA targeted antisense oligonucleotides technology (ASO) to inhibit miR-22 epigenetic activity, thus restoring a healthy homeostat in livers affected by metabolic disorders. Additionally, we are studying the ability of our anti-miR-22 compound to act as a tumour suppressor, inhibiting cancer cell migration and invasion. Research undertaken thus far has shown that pharmacological inhibition of miR-22 is effective in protecting mice from MAFLD and obesity via simultaneous modulation of a number of different biological pathways, reversing fat accumulation in obese animals, and opening the door to further developments in anti-MAFLD therapy for humans.  

Resalis Therapeutics have been successful in obtaining seed funding to continue its ground breaking work in this field. Is there anything else which you feel has made a real difference in being able to progress with the research?

Resalis Therapeutics was established on a very slim budget, activities were carefully planned and co-ordinated by myself with a very lean structure, and I feel that the ability to work with minimal overheads has also contributed to us now being in a position to expand. However, research and progress must always be a team effort, and I firmly believe that the key to success is having a strong support group behind you. It’s also useful to make contact with other experts, drawing upon their expertise and skills in order to maintain confidence and resilience during the inevitable set-backs and delays. 

It must be quite a challenge when developments do take longer than expected, or solving one problem perhaps brings up further issues. What do you particularly enjoy about carrying out this form of research?

For me, it’s about being able to look at the bigger picture and realise that the overall aim is to improve the quality of life for patients. While we may have to admit to errors in the event of new knowledge arising, and be prepared to change direction as a result, it’s exciting to be at the forefront of generating new pioneering knowledge in a little known field (microRNA biology) and technology, and explore how these revolutionary techniques will impact the therapeutic area and ultimately play a part in fulfilling an unmet need – that of helping to eradicate certain metabolic disorders.

Finally, drawing on your own personal successful start-up experience, do you have any advice for aspiring entrepreneurs or CEO of start-ups considering their long term strategies?

I think it’s vital to be creative and to be able to move in a complex and continually changing environment. Ask questions, analyse pros and cons, consider the risks of doing things versus the risks of not doing them and concentrate on long term goals. Success is often achieved via a fine balance of advance planning whilst being able to act urgently and change direction at any point.

I’d also advise against taking established knowledge for granted. It’s important to question the value of an intervention (especially in the medical / biopharma sectors) rather than carrying out processes in the same way as they may have been done for many years previously. Success lies in being able to think beyond what is known, to find what is possible or meaningful in that specific setting. 

I always keep it in mind that any innovative techniques, processes or procedures are exactly that – they’re new, and they involve creating things never done before. With that in mind, we need to understand and be able to explain why our intervention is the correct thing to do. We’re moving in an unknown field and we cannot expect any regulatory authority to tell us exactly what to do, and what is either right or wrong. We need to be able to work together with them, finding the best way to achieve our common goal, safely and effectively address a therapeutic unmet need. The onus is on us to explore, innovate and educate.Resalis Therapeutics is a biotech start-up established to focus on developing therapies for metabolic disorders, as well as oncology and liver disease.  For further information on the science behind their revolutionary techniques, please visit the company website – https:// www.resalistherapeutics.com