IRLAB: Developing drug candidates with ‘blockbuster potential’ in Parkinson’s

Gunnar Olsson, CEO of Swedish biotech company, IRLAB, speaks to NR Times about its ‘blockbuster’ drug candidates which aim to tackle major unmet needs in neurodegenerative diseases. 

Parkinson’s is the most common primary neurodegenerative disease after Alzheimer’s, affecting nearly nine million people around the world. This figure is expected to double by 2040 in line with an ageing population. 

Rooted in the Nobel Prize-winning research of Professor Arvid Carlsson, who was best known for his work exploring the role of the neurotransmitter dopamine in Parkinson’s, IRLAB, is developing innovative treatments to tackle unmet needs in Parkinson’s and other neurodegenerative conditions. 

The company has developed a unique technology platform known as ISP to discover new drug candidates for the central nervous system. 

Based on advanced machine learning techniques, ISP taps into IRLABs proprietary CNS pharmacology database to inform its team of chemists about the optimal molecular design of potential drug candidates with the desired therapeutic effect. Using ISP is not only said to increase the pace of drug candidate discovery, but also its probability of success. 

So far, the platform has been crucial in the development of a portfolio of five drug candidates, with what is known in the pharmaceutical industry as ‘blockbuster potential’. In other words, they could hold major promise for the lives of patients as well as the company’s position as a world-leading pharmaceutical business.

One of its main candidates, pirepemat has the potential to become the first treatment for the largest unmet need in Parkinson’s, prevention and reduction of falls and fall injuries.

An ongoing Phase IIb study, React-PD, to evaluate the effects of pirepemat in patients with advanced Parkinson’s has been running at 38 clinics since May 2023, with enrolment expected to be completed in the third quarter of this year. 

Findings so far indicate a “great possibility” for a first-in-class drug for the treatment of falls in Parkinson’s that can “change the treatment algorithm to benefit patients and their families”.

At this crucial time for the company, CEO Gunnar Olsson, spoke to NR Times about this, as well as the other promising advancements to come. 

Can you give me an overview of IRLAB and its current focus?

We are here to develop new medicines that should transform the life of patients with Parkinson's disease and other neurodegenerative diseases. There are about 11 million people living with Parkinson's and with quite a rapid increase predicted over the next 15 to 20 years. Our focus has been based on situations or symptoms with very large, unmet medical needs in the Parkinson’s population. 

We have developed a very unique platform to identify and discover new molecules. This is what we call phenotypic screening based on a systems biology approach. What this gives us is very high novelty that, of course, puts us in a good position for IP, which is important for us as a company, but more importantly, it has shown that we have a higher success rate than industry standard with regard to the molecules that we select that go onto have success in clinical testing. 

Today we have a portfolio of five projects, stemming from early preclinical development up to our most advanced project that is now ready to go into Phase 3. We believe that a lot of very fascinating things will happen for us over the next 18 months.

One area of research you are working on, is in the treatment of falls in Parkinson’s. Can you tell us more about this?

Our second compound is pirepemat and that is a treatment that we are developing to reduce the risk of falls in patients with or individuals living with Parkinson's. We know that from patient surveys falling and balance problems are the most frequent and the most feared symptoms by patients. Roughly 50 per cent of individuals with Parkinson's have recurrent falls, but today there is no available treatment for it. Right now we are in a Phase 2 study that is running across Europe to determine the right dose that should be produced in Phase 3. We're very excited about this and we had some very promising data in our Phase 2A study.

Can you explain the mechanism behind pirepemat and how it works?

What is known, is that the transmission between deeper parts of the brain and the frontal cortex in the brain, is significantly reduced in those that have an increased tendency of falling. We are using an inhibitor of Alpha two and 5HT7 receptors. By doing that we significantly increase the nerve transmission between the deeper parts of the brain and the frontal cortex, which then enables better balance and a lower risk of falls. 

What are your predictions for how this candidate is going to perform in more advanced studies?

I think that from the Phase 2a study, we had quite a significant effect in terms of the magnitude of effect, of course, with Phase 2a you have small studies meaning that the precision is a little bit uncertain. That's why in this study, we have more patients. But we believe that this will have a very clinically meaningful effect. We anticipate that if this works the way we saw in the Phase 2a study, then it's in the region of 40-50% reduction. But, of course, we need to be a little bit careful here and will have to wait and see the results. 

What can you tell us about your newer drug candidates? You also have a number of other candidates targeting different symptoms in neurodegenerative disorders, including apathy and cognitive impairment. Which candidates are you most excited about?

I think that all of these have the potential to be what people in the pharma industry usually call ‘blockbusters’, meaning that they could really become enormously successful. The closest in time is mesdopetam (IRL790), which is now ready to go into Phase 3. But I'd say that we are at least as excited about IRL1117 [aimed at offering a once-daily oral treatment for the hallmark symptoms of Parkinson’s without inducing the troublesome complications caused by today’s mainstay anti-Parkinson’s levodopa treatments]. If we could get away from all the levodopa negative complications in the long run, that would have fantastic effects for patients. 

That is really what has led us in all our projects, and that is to try to find completely new things where there is very little or no therapy at the moment, so that it really could make an impact on people's life.

Why do you think IRLAB has been so successful in the development of these potential treatments where others haven’t?

I think it is our discovery platform. Most pharma companies nowadays are using what is called a target-based screening model when they look for new molecules, that means they are looking at one single target at a time. For most vital systems in the body and brain then you need to have many safety systems and that is what people call redundancy systems. What that means is that you have the duplication or triplication or even more systems so that if one system fails, the other one comes in because otherwise you would die. And that means that when you go with this target-based screening and you just take one thing at a time, very often you don't see any effect at all because something else counterbalances. 

Using today's terminology, we've been using AI Artificial Intelligence for 25 years. We collect a lot of data and everything goes into the database and therefore when we do an experiment in the animal we could read into our system and the system then tells us what will be the effect in clinical use. Then when we find a molecule that fits what we want it to do, then we start to characterise it and that means that most often we see that our molecules are not just hitting one target, but two or three or four. Our molecules are almost like a combination therapy in one molecule. We believe that that is why we have a higher success rate when we compare to industry standards. 

So what sort of timescales are we looking at? When might these drugs actually be available for patients?

It is, of course, guesswork, but we believe that a product like mesdopetam, our most advanced molecule, could be on the market as soon as late 2027-2028, so it's not that far away. 

You may wonder why I can say that the product could hit the market in not too long a time because when you're dealing with neurodegenerative diseases, you usually have very extended times. 

Alzheimer’s molecules are slowing down disease progression, and that means that you need to wait until the untreated has progressed and that takes time, but with our compound we are hitting certain parts of the brain and measuring beneficial effects directly, so within three months,  we can detect the effect.