Kizoo Technology Capital has a clear aim – to develop drugs that abate or cure age-related diseases. Lu Rahman spoke to owner, Michael Greve to find out more about this exciting work that aims to make age-related therapies affordable for everyone.
Kizoo is investing €300 million in a portfolio of private science-backed biotechnology companies which are working to tackle age-related diseases. The funds underline Kizoo’s commitment to these start-ups with the aim of advancing therapies from clinical development to patient. It’s a grand proposition, but owner Michael Greve is very clear on his pursuit of these goals. “It’s a personal thing for me,” he says. “I have a strong background in technology and have created several big technology companies and internet companies in Germany. I sold them and went into venture capital; parallel to that I was interested in my own health.” Greve believes this interest is key. “You can look after your lifestyle but eventually you come to realise you can’t diet yourself healthy forever. Sooner or later you’ll be susceptible to age-related diseases due to the ageing process. This is how I became interested in this field. Basically, all my entrepreneurial energy shifted to this area – rejuvenation biotech.” Greve acknowledges that globally there has been a significant shift to learn more about age-related diseases (ARDs) and that we have reached the point where we can keep them under medical control. “Of course, we are not fully there yet but it’s very exciting and is something I and my team want to contribute to – the acceleration of that development. This is really what drives us,” he explains.
Of course, ARD is a broad clinical area – anything from osteoporosis to some forms of cancer. “Basically, we’re talking about all age-related diseases because the field that we are working in is focussed on the root causes of these diseases. We’re not talking about fixing a particular disease but about understanding what causes these diseases in the first place.” Greve explains that there are two paradigms that are similar. One is the hallmark of ageing and the other is the Strategies for Engineered Negligible Senescence (SENS) paradigm, which goes to the root of the issue. “We have found that there are seven to 10 root causes, ie. things can go wrong on a molecular and cellular level. Ultimately the effect of this can be cancer or heart disease, for example.”
Greve and his team are working on the root causes to therefore prevent ARDs entirely.
Areas of opportunity
According to WHO1, by 2030, one in six people in the world will be aged 60 years or over. At this time the share of the population aged 60 years and over will increase from 1 billion in 2020 to 1.4 billion. By 2050, the world’s population of people aged 60 years and older will double (2.1 billion). The number of persons aged 80 years or older is expected to triple between 2020 and 2050 to reach 426 million. Greve recognises the size of the opportunity in this area. “In the end it’s about breaking the ageing process down into sub processes that you try to repair or counter. Of course, to bring a product to market you have to have an indication – ageing is not a valid indication so it’s necessary to focus on a specific disease such as cardiovascular, heart attack or stroke. Potentially, focusing on this root cause enables us to get rid of, for example, 80% of heart attacks.” Kizoo’s strategy is to define this as a new sector in drug discovery but Greve is clear that the business is not a regular venture capital company. “We are mission-driven. Our background highlights how we have been successful with our technology investments. Our intention now is to bring this field of rejuvenation biotechnology forward. It is a completely different approach to most medicine because this is a preventative approach.”
In order to drive this field, Kizoo makes what it calls ‘lighthouse investments’. “These are part of our investment paradigm and are things that have never been done before but have the potential to become game-changers,” explains Greve. “We have several points that we want to prove with our investments. When we talk about age-related diseases and rejuvenation, many people think it’s science fiction. We want to show this is not the case and that the reality of a pill or an injection to tackle the root cause is possible. We also want to demonstrate that it’s going to be inexpensive and that the therapeutics will be for everybody. Finally, we want to make the public understand that what we are trying to do is uncomplicated.”
One of Kizoo’s start-ups is Underdog Pharmaceuticals whose goal is to deliver a simple and affordable preventive therapy on a global scale. The company develops easy-to-use drugs that prevent common age-related conditions such as atherosclerosis, heart-attack and stroke by addressing the root cause – a build-up of arterial plaque. Underdog’s technology removes arterial plaque by clearing the non-degradable cholesterol that accumulates within cells in the arterial walls.
Underdog’s research has combined computational and synthetic chemistry programmes to create custom-engineered cyclodextrins (polysaccharides with known industrial and pharmaceutical excipient uses) to capture, and remove from cells, oxidised cholesterol derivatives such as 7-ketocholesterol, which are broadly toxic molecules with no known biological function.
“The result of this research is the development of a molecule that’s a special type of sugar and we hope this can be consumed as a pill into the bloodstream, enter the artery walls and macrophages, travel into the lysosome, grab the oxidised cholesterol and transport it out of the lysosome and macrophage and be excreted like any other waste from the body,” says Greve. “In effect, we can turn an old artery into a new artery.”
Underdog is hoping to go into clinical Phase I next year. “We hope we can move to patients next year or the year after and then we will know if it works or not. It’s a good example of what we want to do and is cheap – it would cost about $10 a month. Everyone over the age of 40 has plaque building up in their arteries – some faster, some slower – this would be a great preventative treatment,” Greve adds.
Other technologies pioneered by Kizoo’s startups include the decalcification of aged tissue, breaking of protein-glucose cross-links and the delivery of new mitochondria to aged cells. These aim to prevent and repair age-related conditions such as myocardial infarction, stroke, high blood pressure, tissue stiffening, skin ageing and loss of muscle function. Therapies like this would also take some of the burden out of healthcare systems if they can reduce the number of people presenting with age-related issues. “While this area of drug discovery has a humanitarian aspect, it is also a big cost-saver,” says Greve.
No drug discovery process is without its challenges. “One is that we need a surrogate indication,” says Greve. “We have to focus on a specific disease, as ageing is not recognised as a disease in its own right. Another issue is that there are no good biomarkers for ageing itself. So the focus right now is treating individual root causes.”
Greve recognises that he and his colleagues are attempting to accelerate a new, young field. “It would be great if we had more researchers working on it, more translational research, more VC money flowing. However, our work is already accelerating and we must remember that these are treatments for everyone on the planet. We all age in the same way, so we will all benefit from such therapies.”
Greve is positive about the future for age-related diseases. “This will be the biggest industry the planet has ever seen. Imagine a life without cancer, heart disease, stroke – without any age-related diseases. It’s huge!”
Volume 23, Issue 2 – Spring 2022