DDW’s Diana Spencer speaks to Peter Hamley, Chief Scientific Officer of Samsara Therapeutics, to understand the role autophagy plays in neurodegenerative diseases and how boosting this process could increase healthspan.
DS: Samsara’s autophagy inducing candidate SAM001 will be the first agent of its class to enter clinical trials. What is autophagy? How does SAM001 work?
PH: Autophagy is the cell’s recycling process. It is the method for removing unwanted debris, e.g., old proteins, and breaking them down so their constituent parts can be used again. It happens all the time in all the cells of your body and it has been shown that we can boost it by healthy activities such as exercise and intermittent fasting. But it’s now known that if it stops working this can lead to many different diseases. The ones we have focussed on, because the data is so promising and the opportunity so big, are neurodegenerative disorders, in particular Parkinson’s disease and Amyotrophic Lateral Sclerosis (ALS). In most forms of neurodegeneration, toxic protein aggregates build up in the brain and the body’s only method of removing these is via autophagy. But as the aggregates build up, autophagy stops working. So, our hypothesis is a simple one – boosting autophagy will lead to removal of the toxic proteins and in addition restore health to the cell, since well-functioning autophagy is so important to this. And we’ve shown that, at least in animal models of these diseases, our drug molecules work really well.
DS: Your research has so far focused on Parkinson’s disease and Amyotrophic Lateral Sclerosis (ALS). What is the potential for this type of therapy in treating other neurodegenerative disorders?
PH: It seems like most of these disorders are at least in part driven by toxic protein build up. For example, it’s quite well known that a protein called beta-Amyloid is a hallmark and probable cause of Alzheimer’s disease, the most common form of neurodegeneration. Again, boosting autophagy in the brain can remove beta-Amyloid and we have already shown improvements in animal models of the disease with our drugs. And indeed, there are other similar but rarer disorders featuring protein aggregation that we’d like to investigate.
DS: Why do you think there haven’t been any therapies targeting autophagy before? What are the challenges of research in this area? What is unique about your approach?
PH: This is a relatively new area of biology and it takes many years to get a new drug to the market. There are some older drugs which appear to influence autophagy but this may not be their main mode of action or they may have a lot of other issues which restrict their use. We’re the first and so far, only company to concentrate solely on autophagy as a therapeutic approach. This means we’ve built up a lot of expertise in what is a very complicated area of biology. We have several therapeutic programmes and although they all have different biological mechanisms and targets, they are all autophagy inducers.
DS: What role does genetics play in autophagy? Could therapies like these treat rare genetic conditions?
PH: Genetics plays an enormous role. There are many mutations in specific genes that have been shown to disrupt the autophagy process and lead to disease. In fact, some variants of Parkinson’s and ALS are genetic in origin. Furthermore, many diseases which are due to specific genetic mutations are diseases, analogous to neurodegeneration, that are driven by the build-up of misfolded, aggregated proteins. As an example, we have a programme to treat the rare muscular skeletal disorder Charcot Marie Tooth 1A, and the results so far are very encouraging.
DS: There has been a lack of funding for biotech companies in the UK and Europe in general in recent years. Has this been an issue for Samsara and how have you overcome this?
PH: We have been very grateful to the support of Apollo Health Ventures, who invest in and create new start-ups in the area of longevity. Autophagy, as explained above, is central to the longevity process. Even though the first diseases we want to treat are neurogenerative disorders, an autophagy inducer holds the promise of generally increasing healthspan (the idea that as you age, you can age more healthily with less chance of succumbing to debilitating diseases in later life). There is a lot of investor interest in this area at the moment, which has certainly helped Samsara.
DS: How easy was it to transfer theoretical research into a viable business? What advice do you have for other start-ups hoping to launch in a similar field?
PH: You need resources but it’s also vital to assemble a really effective team. We have a combination of talented and motivated young scientists along with experienced industry experts who have been through the process of drug research and development. This is essential since it’s an extremely complex endeavour and experience is vital to improve the chances of success.
DS: What’s next for the company’s pipeline? What impact could autophagy inducing therapies have on lifespan? Could it be possible to prevent genetic diseases?
PH: As well as starting clinical trials with our most advanced programme, SAM001, we have two more highly promising programmes that we want to advance to the clinic in the next year or two. But we also want to develop autophagy agents for other diseases where the process is implicated, such as fibrotic diseases or even cardiovascular disease. Genetic diseases that are driven by toxic protein build-up could be treated in just the same way as we plan for neurodegeneration. As to lifespan, as mentioned above an autophagy inducer should not only increase lifespan but healthspan, which is really the goal here. Not only would this be good for the person, but it would also reduce the burden on healthcare systems by keeping people out of hospital.
Biography
Peter Hamley, PhD, MBA, is Chief Scientific Officer of Samsara Therapeutics. He is a recognised leader in drug discovery, having spent 15 years at Sanofi, most recently as Global Head of External Innovation, Drug Discovery in Business Development. Prior to this, he led global high throughput medicinal chemistry, natural product and antibody drug conjugate departments across Germany, France, and the US, and has contributed to the advancement of many projects into clinical development across several therapeutic areas. LinkedIn profile.
