Dr Jus Singh (PhD Computer-based Drug Design)

The following blog is a transcript of an episode of #OurBirkbeck: Conversations with Alumni Podcast. Listen to the full podcast here

Speaker 1: Hello, and welcome to the Our Birkbeck podcast. Our Birkbeck is an exciting year-long initiative to share and showcase the impact members of the Birkbeck community are having around the world. In this podcast series, you’ll hear from our alumni, students, staff and friends, whether they are making a difference in their community, bringing about change to their industry, or shaping the lives of those around them  – we celebrate their story. To find out more about the Our Birkbeck initiative, please visit campaign.bbk.ac.uk.

In this episode of the Our Birkbeck podcast, Finn Judge from Birkbeck’s development and alumni team interviews Dr Jus Singh.

Finn Judge: Hello I’m Finn Judge, development officer at Birkbeck, and welcome to this Our Birkbeck podcast. I’m joined by Dr Jus Singh, founder and chief scientific officer at Ankaa Therapeutics. Thanks for joining us for this Our Birkbeck podcast interview Jus, it’s great to have you with us, and it would be really good if you could just start by telling us a bit about yourself and the work that you do.

Jus Singh: Yeah, well thank you for the opportunity to speak. Start by saying that I studied at Birkbeck from 1981 to 1984, I’m a scientist, an entrepreneur and had the opportunity to do my PhD at Birkbeck in the early eighties. I now work in the United States and have worked for the last thirty years in the field of biotechnology. Married with three kids, four grandkids and live in Massachusetts. In terms of my work, it focuses on the intersection of computers, chemistry, biology and pharmacology – and the idea is to create drugs and impact human health. In terms of before I came to Birkbeck, I grew up in the North of England, in a place called Stockton-on-Tees, and my mother who is an inspiration to me, raised us on her own, three girls and two sons – and to some extent it was an area of the country that was pretty poor and opportunities were not that many, and I think at that point I realised the importance of education, and I think Birkbeck highlights that importance of education to students, and how it can create opportunities. I think at an early age I realised that education was the way to get out, and to be able to make an impact. I learnt how to basically teach myself certain subjects, and to some extent I think that teaching of myself, helped me try to be able to create things, and I think that’s helped me a lot in my scientific career. I wanted to study geography, history and economics at school, but when I went into my sixth form college they told me no you’re going to study chemistry and biology – which I knew very little about – and from there I ended up going to study Bio-chemistry at Sussex, and then I did my PhD at Birkbeck. What happened there, in terms of Birkbeck, was that I got a telegram from Tom Blundell, who was setting up the crystallography unit of Birkbeck, and he said would I be interested in coming to Birkbeck, and checking out the PhD programmes. And he had this very interesting project which was using computers to design drugs, and it was an area that was emerging at that time and I found it very exciting and I ended up basically going there and spending three years on my PhD. Now after the PhD I did a short post-doc, and I decided at that point I wanted to basically move to the US, because I thought the US would be a greater opportunity to develop drugs, and that’s where I’ve been now for the last thirty years almost, so it was a tough decision to leave England and move to the US, but I think in hindsight it was good because I think America at the time was a great place to be in terms of infrastructure, expertise, people, to be able to do some very, very exciting things in terms of developing drugs.

Finn Judge: So Jus, you’re now at the forefront of developing covalent drugs after your time at Birkbeck and after you moved to the US, and if you could tell us in layman terms, what the science is behind covalent drugs and how these have made an impact on treatment of cancer patients which I know you’ve recently been recognised for, by the American cancer society.

Jus Singh: Yeah, in terms of, if you look at the last century – the 20th century – one of the major advances has been the discovery that proteins in the body can impact disease, and that therefore modulating the activity of those proteins can ultimately lead to treatments, for diseases such as cancer and autoimmune diseases. I find that actually pretty remarkable, that a single protein can have essentially a direct influence on a disease. Now, that whole area which is called ‘rational drug design’ – that you know the protein, and that if you can impact the right protein you can impact very complex disease – has led to companies and academic institutions working very hard to try to figure out what is the right drug for a particular protein that is essentially not working properly in a disease setting, and if you look at what those drugs in terms of their mechanism, there’s essentially two types, one which is essentially the predominant mechanism, it’s called ‘reversible drugs’ which drugs come onto a protein in your body, and then they come off. There’s what ends up being in a thing called ‘equilibrium’ and companies work very hard to develop drugs which will essentially stay on the drug market, but it’s not an easy thing, it costs lots of money to be able to develop the right drug to do that. There’s another area called ‘covalent drugs’ and what they do is they come onto a protein target and never come off, it’s called ‘irreversible’. It’s a very scary term that word ‘irreversible’, and essentially its led to companies avoiding that mechanism of action because they felt as though there was risks associated with that concept of a drug not coming off its target. Now, that area I found very interesting from a historical perspective and the reason is some of the most important medicines in our Pharmacopoeia, work through a covalent mechanism of action. Drugs like aspirin and penicillin which potentially many of the people listening to this might have taken. They work through a covalent mechanism of action, and they were discovered a long time ago, and the interesting things is people didn’t realise the mechanism when they first discovered those drugs, and yet they’ve had a profound impact on human health. The thing was there seemed like a disconnect with historical impact of covalent drugs, and yet modern drug discovery programmes didn’t use them. And I set out to figure out if there was a way, what problems could you solve through a covalent mechanism of action, that could not be done through a reversible. That was the formation of a company called ‘Avila’ and we ended up targeting two proteins in the body, one is called ‘mutant EGFR’ and it turns out that’s very important in terms of lung cancer, about fifteen years ago a pivotal discovery was that a mutation happens in EGFR in the body of patients, and it turns out it leads to lung cancer and it’s not due to smoking, its due to that mutation. That disease became essentially the poster child for targeted therapies, if you could inhibit that epidermal growth receptor EGFR, you could essentially see these profound effects in these cancer patients where their tumours would shrink, and they didn’t need to be on these toxic chemotherapies, the drugs themselves are relatively mild. So that was a breakthrough, the problem was, within a relatively short amount of time, all of those cancer patients, their tumours would come back, and it was due to a thing called ‘resistance’, and it turns out the covalent drugs are able to work on those resistant mutations, and completely knock them out. And that ultimately has led to a new generation of drugs called ‘covalent mutant EGFR drugs’ which one doctor at Mass general hospital called it a miracle in the patients’ lives. That those drugs were able to be well tolerated, and give these people hope, so that was one area that covalent drugs made a profound impact. The second is a disease called ‘chronic lymphocytic leukaemia’, it’s the number one Leukaemia in the United States and Europe, and up until the point where these covalent drugs came up, it was a disease that was very difficult patients, they were on chemotherapies which weren’t very effective, it’s an elderly population who essentially don’t do well with these chemotherapies, and these covalent drugs have literally revolutionised the treatment of chronic lymphocytic Leukaemia. Once again, you’re seeing survival curves which essentially lead to patients being able to survive longer, and not have to take very toxic regimens of chemotherapy. So I’d say, those are two examples of drugs that have been impacted-sorry diseases which have been impacted by covalent drugs, and it has changed the perception of covalent drugs in the industry.

Finn Judge: That was fantastic, and of course you’ve had to combine that scientific acumen with business acumen in taking these drugs out to market and you were successful founder of Avila which was acquired by Celgene and I’d be curious to know, what does it take to combine both kind of business sense and the science in pushing those drugs and getting them developed?

Jus Singh: Yeah, I think that in terms of the advancement of drugs, it’s a rocky road, and it terms of Avila I think we made a lot of great progress in terms of advancing the whole field of covalent drugs, but getting a drug to market is not an easy thing. It takes lots of money, lots of patience, and in terms of if you look at people who basically want to go down this path, I think that’s the key to have a vision of what you’re trying to do, and often it isn’t something that you’ll succeed in on your own, and just lay the foundations and ultimately others will move these platforms forward. But to some extent I think that’s the key, have a vision, try to stick to it, and it’s going to be a bumpy road, it’s never easy especially with drug development, it’s one of the hardest areas. I’ll be upfront, it’s not been an easy path to be able to go down that road, drug development is basically a graveyard of great ideas that never-ever see fruition, but I think that’s ultimately the slow, steady progress of science, ultimately can lead to ultimately decisive impacts. I think for entrepreneurs, entrepreneurs have got to look at the long term, and that’s not easy because investors want essentially returns on investment within a reasonable time frame, and there is essentially a certain tension between the advancement of, essentially drug development and ultimately what the science dictates. I’d say for the people, it’s having a longer-term vision, to be able to be ready for the ups and downs and believe in what you’re doing.

Finn Judge: And of course, you quoted five years ago that you followed the Pauling principle which is to have lots of ideas, and throw away the bad ones. I’d be interested to hear, and I’m sure listeners would too about how that’s manifested itself throughout your career, and if you’ve had to throw away just as many, if not, more bad ideas.

Jus Singh: Oh definitely, I mean in terms of doing drug discovery, I think one of the things that you realise is, a lot of things that you do will not work, and in terms of my career in bio tech I’ve worked at some other companies, I worked at Parke-Davis in the early nineties, they’re the ones who developed drugs, breakthrough drugs like Lipitor, which has changed the way we treat cholesterol, and also I worked at a bio tech company called Biogen, and what I realised from being at both of those companies, is that most of the ideas never-ever moved forward. To some extent I think that was part of the thing that I found frustrating, that you had all these ideas that you’re permanently stuck in early drug discovery, nothing ever got to humans. I can say with satisfaction that for the work that we did at Avila, we were able to move drugs within a relatively short time frame, about five years into clinical trials and see impact on patients. Ultimately, because we got acquired, we didn’t see the fruitions of it going all the way to a product, I mean those are longer time frames and require much larger organisations, but I say that to some extent, most of the ideas don’t move forward, and even the work that we did at Avila, is still yet to see the light of day. The other thing to point out, is my career itself has not necessarily been smooth, when I was at Biogen – I was at Biogen about ten years – one of the oldest biotech’s in the US, very successful company, but in 2006 Biogen had a hiccup with one of its drugs in clinical development and they had to restructure so most of the workforce was let go in research. After ten years of building up a group and being very excited, half the work I was doing, I was suddenly left in a situation where you no longer have your group, you no longer have that permanent job, so what are you going to do, and that’s when I started Avila. It wasn’t at the most, like, strongest point of my career, in some respects it was at the weakest point, I decided at that point I wanted to start my own company to advance drugs. Not an easy task, I remember the conversation with my wife saying I was going to start my own drug company, she thought I was a bit crazy because I mean I didn’t have money to start a company and you need all these resources, but I think to some extent it shows that a good idea at the right time in the right place, can ultimately lead to an impact. That isn’t to say I did it on my own, I was fortunate to have people who were very supportive of what I was doing, European investors as well as US investors, and ultimately be able to build up a great scientific team. But I think to some extent it just shows that it’s the idea that’s important, and then you have to nurture that idea and you have to deal with the ups and downs of it. When we were developing our company, we essentially were raising money at the collapse of the financial markets in 2008, probably the worst time to be able to raise money, but ultimately, we succeeded. I think that’s just one of the ups and downs, the ups and downs of drug development and the ups and downs of actually trying to make a company succeed. I think it’s complicated but it can be done, and I think it requires essentially a passion for what you’re doing.

Finn Judge: And of course, an environment that encourages and allows for innovation as well, and it was interesting that you moved to the US, so early in your career after your studies, where do you think are the current best places for Pharma and biotech in the 2020s, would you still say the US? I mean you mentioned European investors too.

Jus Singh: Yeah, I don’t know as much about the European landscape, but I do see that there is a huge amount of energy in places like Boston and San Francisco. I worked in Cambridge for a long time, and just looking at the landscape in terms of biotech innovation there, it’s remarkable. Being able to create those hubs of innovation, it’s not easy because you have to have the right intersection between people who are innovators, you have the right group of investors around you who are willing to take these difficult bets, and I think that the US, historically, has just been a very good place to do that, and I think that Europe, when I was there, was not optimal in terms of that. I think things have changed, but I suspect it’s still not got the same level of intensity as you have in the US. If you look at the financial markets in the US, you look at the listings of biotech’s going public, I think there’s just a lot more US companies going public. And that’s a little bit frustrating to some extent because when I was at Birkbeck and looking at the people around me, there were some remarkable people who could have essentially if they’d had the infrastructure of the US, probably could have made companies from that, and the academics that I worked with at Birkbeck like Janet Thornton, and Tom Blundell, I mean you could have seen multiple companies coming out of those innovators.

Finn Judge: Well that was along the lines of the next question I was going to ask you Jus, which was, earlier on in your career at Birkbeck doing your PhD, perhaps far away from the commercial environment in which you have to enter afterwards, what was special about the Birkbeck community that kind of fostered some of the ideas that you eventually took forward. What parts of that community helped you do it?

Jus Singh: So, a couple of things. First is that I think that I was in a great department to do computational drug design. Now, the thing was I started out with a degree in bio-chemistry, and had no idea of computers, and then ended up going to a place where the project was on computers, so it was a steep learning curve, but it was great to be around people who had a lot of expertise in that. I think Birkbeck in terms of the department I was in was great, in terms of getting a theoretical background, and I was around people who were experts in that area, and at a time when things like the human genome project were on the horizon, and the idea of looking more systematically at proteins which are why these critical components to the way your body functions, and ultimately dysregulated in disease, so Birkbeck gave me the underpinnings, the theoretical underpinnings, and then I think moving to the US allowed me to combine that with the experimental. It would have been great if both of those had been available to me in the UK, but I thought the US was the way to combine those two. Another thing that I think was great about Birkbeck was if you just look at the people in the actual offices that I shared, they were just a great bunch of people, very innovative, very diverse in terms of their backgrounds, I think that is a fantastic thing about Birkbeck, it’s just a hub of activity coming from lots of different backgrounds. I shared a room which I think at the time was just a focal point, it was called EP10, and there was a great bunch of friends that I made in that room, who went on to do great things and it was just-I still have friends from that time at Birkbeck, and highly respected the people that I worked with.

Finn Judge: It sounds like you had people from which you could draw inspiration, and that leads nicely to our last question, which is, who has inspired you most? Not just in your career, it could be in your career but in your life generally, leading up to now.

Jus Singh: Yeah, I think that, well I’ve been fortunate to be around some very great women, and I have to give my inspiration to my mother and I think to some extent it ties in with the whole Birkbeck story, and that is, my mother came from India, and I think she ultimately became a single parent and brought up five kids, but what she instilled upon us was the importance of education, and that education was the means by which to basically make opportunities, and there wasn’t many opportunities in the part of the country that we were growing up, and I think to some extent, to see her resilience and her grit and her ability to deal with difficult situations, I think set an example for me throughout my life, she recently passed away and I think to me it basically just speaks to the fact that even to this day, I see her as a shining example in terms of what I could do. In fact, one thing that I was very happy about was that I got the opportunity when I got that award in the US, to take her to San Diego, and I think that award for me was more for her, than it was for me. I think it was just a testament to a lot of mothers – it was Mother’s Day yesterday in the US – who do a great job in terms of basically guiding their kids and obviously parenting in general. I think also, I just want to emphasise again, Birkbeck, a great institution, gives people opportunity through education and I can’t speak enough about how important that is, it’s all about opportunities and keep doing the great work

Finn Judge: Well Jus thank you very much for your time, and I know things are very busy at the moment for you, in the lab and elsewhere so I’ll let you get back to that, and yeah just to say a massive thank you to you once again.

Speaker 1: And that’s the end of this episode, we hope you have enjoyed hearing from Jus and Finn. If you’re interested in finding out more about Our Birkbeck, please visit campaign.bbk.ac.uk to read more about the impact our community is having around the world. Thanks for listening, and until next time.

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