John Simboli 0:00
Today I'm speaking with Clive Richardson, CEO at Akari Therapeutics, headquartered in London, with offices in New York. Welcome to BioBoss, Clive,
Clive Richardson 0:09
Very pleased to be here. Thank you, John.
John Simboli 0:11
Clive, what led you to your role as CEO at Akari therapeutics
Clive Richardson 0:16
Akari Therapeutics is originally a UK company, it was a private UK company. And it developed out of some work done at Oxford University. And I was originally involved in a sort of slightly peripheral role in its early development but was still involved with the company. And then, as it expanded, I became more and more involved and ultimately became the Chief Operating Officer for the company. We listed on NASDAQ, and the role from Chief Operating Officer ultimately turned into CEO of the company.
John Simboli 0:51
Had you known, prior to that, that was gonna be in your future, leading a biopharma company?
Clive Richardson 0:57
I've always really been interested in this space. So you know, it was an objective, whether you ever achieve it or have the opportunity is also an unknown. But I mean, clearly, for biopharma, it's a really, really exciting space, I have a background in biology, it's super dynamic. I'm incredibly lucky to be here, to be honest.
John Simboli 1:18
What were you hoping to achieve when you came on at Akari Therapeutics that perhaps could not have been achieved elsewhere?
Clive Richardson 1:25
So the interesting thing about Akari is the background of the molecule. So the molecule is actually derived from nature. In fact, it comes from the tick, the insect, the tick. And what happens is, when a tick feeds on you or another host, you don't scratch the tick off, because if you did, the tick would fall off and die. So the hypothesis, and this was really developed by a colleague of mine, Miles Nunn, who's the Chief Scientific Officer in the company, the hypothesis was that the tick is injecting, when it feeds it injects through saliva some immunomodulators that dampen down, that make sure you don't get an inflammation at the site of the feeding. From that hypothesis was the idea that clearly there are molecules, interesting druggable, potentially druggable molecules within that saliva. So from my perspective, what sort of makes Akari, in some ways very different, is that this molecule is actually derived from nature. So you're taking a molecule, you know, it's been discovered in nature, you then have to refine it, develop it, turn it into a drug. So that's a wonderful process. And that's not an opportunity you get, in every company. So to take it, literally from nature, hopefully, all the way through to a medicine that is beneficial to patients,
John Simboli 2:40
It occurs to me, I'm sure you've heard this in your conversations, people must say, ticks, they're not very nice animals or very nice creatures.
Clive Richardson 2:48
Absolutely. And, you know, they are obviously carriers of infection as well. But the reality is, lots of animals have to, you know, it's evolution, they have to design, it's not them designing it, but ultimately, molecules they use are refined by evolution. And in this case, nomacopan, which is our lead molecule, has very tight binding, it has two binding sites, binds to C5 and LTB4 very tightly. It's very soluble, has lots of attributes that make it very druggable. And it's almost as if it's been, I mean, it sort of sounds bizarre to say, it's almost as if it's been in the lab for 100 million years, you know, slowly being refined. And that's what was potentially attractive about it. Now, clearly, the conversion from something used by the tick to a drug, you know, there are lots of risks and potential issues along the way. Safety and immunogenicity being obvious ones, but you know, it's now in phase III, and those potential risks didn't turn out to be risks.
John Simboli 3:52
When people say, what do you do for a living, how do you answer that?
Clive Richardson 3:55
I guess we're all really in the business of trying to develop drugs to treat people with diseases. In our case, it's people with very severe and orphan diseases. And I think what interests people, often, I find, is the process that you go through in order to get there. Because it is very complicated. And unlike many other businesses, there are an enormous number of variables. And there's a lot that's not known. And I think that's what people often find interesting. It's, You're pathfinders, you're going into the unknown and issues will arise that you hadn't anticipated but you can't immediately resolve but that's part of what makes it exciting. And the ultimate goal is crystal clear.
John Simboli 4:45
How do you describe your management style when people ask you about that?
Clive Richardson 4:48
My personality is a sort of collaborative personality. Everyone has different approaches. I mean, for me, it seems to be well suited to the biotech industry because you're dealing with a lot of experts. And you don't know everything and you have to collaborate to get the most out of them. Whether it's the scientists, medical, manufacturing, there are so many different parts where you're relying very heavily on people's individual expertise. And obviously, the different parts of different project streams have to all interact and fit together. I find collaboration a very helpful approach. But there are obviously many different ways to run a company,
John Simboli 5:32
As a leader, as a CEO, there's this constant balance point to be found between being collaborative, as you're just saying, and then also having to make decisions, often ones that no one else can make, or no one else really wants to make. How do you go about making that decision? This one, I'm going to step in; this one I'm going to seek counsel on?
Clive Richardson 5:56
You put your finger on a really difficult situation, sort of issue that everyone inevitably encounters. And I think, experience there is super helpful. I mean, the biotech industry, it's a very specialist case, but clearly, you have recurring issues. And those issues may be to do with manufacturing, running clinical trials, you know, some of these things are recurring, and to the extent that you can draw on prior experience, I think it is useful. But clearly, you're also hoping you've got colleagues who have had relevant experience. We've had to make difficult strategic decisions. Early on in the program, we moved our focus from one particular disease area to another and, you know, these are unquestionably difficult decisions.
John Simboli 6:47
Can you remember a time when you were maybe eight or nine or ten, or somewhere in that range? And you wanted to be something? Probably what, for most of us what we thought our parents wanted us to be? Do you remember what that was? And does it have any connection to what you're doing?
Clive Richardson 7:02
Ironically, it does, because when I was young, I've always been very much into biology and nature, etc. And I wanted to work in a zoo, is what I wanted to do. And in fact, before I went to university, I had the opportunity to work in a zoo, which was great. As you got older, I was in consulting and banking and decision support, healthcare software systems. You know, to end up, and it's almost back to the first question, to end up in a company where the molecule is actually derived from nature, is not something you can plan for or expect. Now, it happens to be serendipitous and a wonderful thing, but there's obviously a lot of fortune. And I think I've just been very lucky. But to answer your question, no, I've always been very much interested in biology. So I'm lucky to be here now. I'm very lucky.
John Simboli 8:02
What do you say when people ask who is Akari Therapeutics?
Clive Richardson 8:05
The way I normally frame it is in terms of the diseases we focus on. And we're largely focused on inflammatory diseases where parts of the immune system are dysregulated. And those parts of the immune system that are dysregulated are the parts that our molecule inhibits.
John Simboli 8:23
When people ask about that, let's say when people ask about the mechanism of action, how do you make it tangible?
Clive Richardson 8:30
I think in essence, people do understand that if there is a disease where part of the immune system is dysregulated, and you switch off that part of your immune system, that is a potential form of treatment. And, you know, the immune systems are extremely complicated. There are multiple pathways involved. And I think one of the questions always is, by switching off just the complement pathway, or another pathway, is that adequate? Because clearly, these systems are all cross-talking to each other. This probably really underlies our molecule because it actually inhibits two pathways; it inhibits the complement pathway in a very similar way to Alexion's Soliris, but it also inhibits the leukotriene pathway. And we're really targeting diseases where both these pathways are implicated. And the idea being that inhibiting one or the other would give you a response, but inhibiting both has an additive effect. And that's, really what differentiates ourselves from other companies operating in this space.
John Simboli 9:38
How do your development programs express that vision you just described for bringing together those two pathways?
Clive Richardson 9:44
So our lead program is in a dermatological disease of the elderly called bullous pemphigoid,. And it's treated with potent oral steroids. It's a very, very unpleasant disease, and there's a lot of evidence in some very nice publications. around this, overall of both the complement and the leukotriene pathway in that disease, and we did quite a lot of preclinical work and in animal models, you can demonstrate what I was saying earlier, that if you inhibit for complement pathway, you get a certain amount of improvement in blister coverage. Likewise for the leukotriene pathway, but together, you get this additive effect and also the complement leukotriene pathway also inhibits a multitude of cytokines downstream as well. And they're also known to be implicated. So I think in that case, there's a lot of evidence for the combined role of complement and leukotriene. And that theme tends to run through our other programs.
Clive Richardson 10:42
So we then have a program to treat Thrombotic Microangiopathy, and, in fact, one of the markers of treatment is elevated complement. There's a lot of evidence of a role of complement, less, to be honest, of the role of leukotriene, in this particular disease, but it's almost certainly involved and there's indirect evidence of its involvement.
Clive Richardson 11:07
Those are both orphan diseases. And then we have other, earlier-stage programs, just in phase III. We then have some earlier programs in the eye and the lung. And again, there's lots of evidence you can get, for example, in tear fluid or tissues for the surface of the eye, complement and leukotriene, in the back of the eye there are lots of companies now trying to treat dry AMD through the back of the eye. And, unusually, perhaps, the leukotriene pathway also inhibits VEGF, so you get this access, inhibiting complement, and VEGF via LTB4. And then, in the lung, there are already approved leukotriene inhibitors like Zileuton, in the lung, and complement's increasingly been known to be involved in the lung. And so, each story is slightly different. But there is this common theme. But before you tackle a disease, you want to be as confident as you can, that the underlying science is valid. And that is a theme across these. So we're trying through preclinical models and other modeling techniques to verify that in principle, inhibiting complement leukotriene is a rational and sensible approach. And then obviously, you have to test it.
John Simboli 12:24
When people misunderstand what Akari is about, what do they tend to misunderstand? How do you get them back on track?
Clive Richardson 12:31
It's a very interesting question, that. When you have two modes of action in a molecule, so here, we're explaining the complement pathway and the leukotriene pathway. So people often ask about relative roles, how important is one compared to the other? Are they both really important? Now, that's not necessarily a misunderstanding, but it's certainly an area where you tend find you're explaining it a little bit further or going into detail. That's the reality is you have two modes of action in one molecule, which is clearly, in many ways, very exciting, but just a little bit more complicated.
John Simboli 13:17
When people see that, and they don't see the category that what do you do? What do they tend to see? How do you get that clarified?
Clive Richardson 13:26
The pigeon-holing is around complement. So the complement space is now, courtesy of Alexion and various other companies that have had drugs approved, you know, it's an established modality. And so people will tend to pigeon-hole you in the complement space. Because of Alexion, it's far better understood, far better characterized than, say, the leukotriene pathway. So we will often be lumped into that group. So then, you know, what we need to explain is yes, absolutely, we do inhibit C5 in the same way as Alexion,. but we have this additional functionality. And that's what differentiates us, this additional inhibition of leukotriene which, we believe, in certain diseases very, very relevant and in certain diseases, clearly, the leukotriene pathway, may be more relevant. But they're both parts of the innate immune system. So it's not surprising or unusual that they might be acting in concert or together in a particular disease.
John Simboli 14:24
Do you find that you can carve out time, on occasion, to step away for a moment and say, you know, if this thing works out the way I hope it will, for patients, it's going to be potentially quite significant. It's going to really change people's lives. Or do you just have to be so focused and that becomes something for later?
Clive Richardson 14:43
In the biotech industry, you have to be an optimist and you're always looking forward. You're looking for what may happen. And in this case, we're very much focused, like other companies working on the immune system on some really, really nasty diseases, some of which are very rare. And they're difficult to treat. And that's the point of a reason they are still issues for patients is because they're complicated. There are all sorts of complicated aspects of the immune system going on. And I think again, this is where we think these two pathways may be particularly important. So I think, to your point, I mean, you do look ahead, you do think, this will be amazing. Like many companies in our space, you interact with patient groups, patient organizations to help understand it from the patient's perspective, from the clinician's perspective. And I think even if you wanted to take a step back, you sort of can't; inevitably you get drawn into the reality of the patient's day-to-day lives. And you have to think about your trials and how you develop your molecule in that context. So I think both from a positive perspective, which is the ambition to do something, and also just from a practical perspective, you do think about it quite a lot actually.
John Simboli 16:04
Can you describe in a general way, just how nasty these diseases are, that you're working on?
Clive Richardson 16:10
So in I think we mentioned in bullous pemphigoid, this is a disease of the elderly. So a particularly fragile patient group. Blistering diseases, incredibly uncomfortable, the current standard of care, potent oral steroids, very unsatisfactory, with lots of side effects, and an increased mortality rate, probably six-fold, so that is a really nasty disease where clinicians, what they want is a treatment that will work really, really quickly. So you can take patients off steroids, and that's what we believe we have with nomacapan. And that's what our phase II data seem to show. So that's bullous pemphigoid
Clive Richardson 16:11
TMA, that's a pediatric disease that's really in its severe form has about an 80% mortality rate. That speaks really to itself. It's a really difficult disease. And these children are very, very ill.
Clive Richardson 17:09
And then in the eye and the lung, in the lung, we're looking to treat exacerbations. So that's the worst form of asthma, COPD. And that's, you know, what hospitalizes patients, This isn't the sort of long-term treatment, this is treating these really difficult, often exacerbations triggered by a virus or something else that hospitalizes and tragically sometimes leads to death.
Clive Richardson 17:33
And in the eye, these are diseases that may lead to blindness. And the reason we're able to develop treatments for these is because, as mentioned before, you know, these are just difficult diseases. And, you know, it's like Alexion, with PNH, there was no really adequate treatment for PNH. We're fortunate that there are things like these orphan programs that support it and make it easier, but we're looking at both orphan diseases, so bullous, pemphigoid, and TMA. And then in the lung of the eye these are much larger, you know, we were talking about, you know, exacerbations in severe asthma or dry AMD, you know, these are much larger diseases as well. So it's not just the orphan diseases, it's often these larger diseases, aspects of it aren't adequately treated.
John Simboli 18:27
What makes a good partner for Akari Therapeutics?
Clive Richardson 18:30
Where we look for partnering is obviously in areas that aren't necessarily fields of expertise ourselves. So if we go back to your prior question where we were going, looking at the different diseases, the lung and the eye, which are target groups for us, are very specialized areas and come with expertise, whether it's in delivery systems, or trial design, etc. And I think for us, you know, partnering in those areas would be helpful for us because, you know, the partner brings expertise and knowledge and scale that we don't have. So I think you're looking for a complementary set of skills,
John Simboli 19:11
What kinds of people thrive at Akari?
Clive Richardson 19:14
You know, we sort of maybe touched on it earlier, when, when we talked a bit about collaboration. And I think, again, I think that's a theme. I mean, clearly, you're looking for people who have underlying expertise in a particular area that they work in, but, you know, especially in smaller companies, you can't work in a silo. And there's a lot of collaboration, people have to work together and that requires a certain mindset where you're very happy to work with your colleagues, help them and, and I think, you know, it's probably true of many smaller companies, not just in the biotech space.
John Simboli 19:50
Clive, what's new at Akari Therapeutics?
Clive Richardson 19:52
I think what's changed is that we are now into phase III programs. And that's a massive milestone. A couple of years ago, I could have articulated, probably, the same story. You know, if we'd been having this conversation, the story would have really been the same, you know, C5, LTP4, the underlying hypothesis. But what's different is, you know, people say, Oh, that's very good, but validate it. And so what's happened is, we've collected more data, we have phase II data, and we now in phase III, have a regulatory pathway, we have manufacturing, we've got to the point where we've sort of delivered on all the prerequisites to get there. And I think that's what changes that's what's new is, you start off in a company, a lot of it is conceptual. And then you go through different stages, but we're, you know, we're now a phase III company. And I think that is a really big new thing, if that's the right word, and it's super important. And in parallel to getting in phase III, I think, also, our eye and our lung programs have also come along a certain way. And, COVID, for example, has been something that I think has brought a lot of attention back to the lung in certain more severe, you know, things like exacerbations COVID pneumonia, that has brought a lot of attention to the lung, and the underlying pathways that are driving that. So I think that's been very helpful for us. And then in the eye, there is now data that pretty categorically demonstrates the role of complement in the back of the eye. And that also gives us confidence in our eye program. You have to take an overview about the pipeline. And, you know, in a smaller company, there's always this challenge between focus and risk diversification. And that's a difficult balance. And in our case, the way we focused on this is to have these two orphan diseases we're targeting but, you know, one's a dermatological disease, one's a hematology disease, very different underlying drivers of the disease. And that obviously gives you some risk diversification. And then we're looking at these larger diseases in the eye and in the lung, where,, as we touched on earlier, we may ultimately look to partner some of these programs. When you look at the portfolio as a whole, that's what we've tried to do to sort of have these orphan programs that we're driving forward in phase III, these slightly earlier stage programs with bigger diseases where we, hopefully, will partner. Have we got the right balance between focus and risk diversification? One never knows, but I mean, it's always, in the back of one's mind,
John Simboli 22:59
How did Akari choose to make its headquarters be in London, and to have offices in New York?
Clive Richardson 23:04
So London is a sort of historic reality. I think we mentioned earlier that the drug was developed in Oxford by part of a National Environment Research Council. So the origin of the drug is the UK and clearly, London's a big center. So why it originated there. And then in terms of New York, I mean, I think, as we all know, you know, for the biotech industry, America is the epicenter of biotech. So ultimately, you have to be in America, whether it's for finance, to work with partners, to recruit the expertise we touched on earlier. You always get dragged towards the states and I guess anywhere along the east coast. So that explains the London New York axis,
John Simboli 24:06
is there anything about working in London or New York that is similar to different or from any of the other biopharma centers where you have worked?
Clive Richardson 24:17
The reality is, is just the US has created this center of biotech expertise. it sort of becomes self-fulfilling because, you know, success attracts more companies, more individuals, more investors. Quite frankly, London does not have that same weight of expertise. I don't think I'm probably expert enough to discuss the differences between, let's say, Boston as a hub, and San Francisco or whatever. But I mean, unquestionably, America, has become the world's center for biotech, and you have to tap into that, to be honest.
John Simboli 25:04
What do you find are the effective ways in terms of connecting to organizations to get the word out about Akari and also to bring information in?
Clive Richardson 25:14
I'm sure we all wonder what would have happened if this pandemic had been 20 years ago. I think it would have been a very different experience for all of us. One of the challenges for our company is to use these media in a more efficient way. And especially in terms of communication. Because, you know, one thing about the biotech industry is that it still does have is the importance of the whole periodicals and articles and peer-reviewed journals. I mean, that remains an incredibly important part of this industry. And clearly, the speed, the turnaround, now on some of these articles is much faster, which is a great thing. But from my perspective, being based in the UK, I used to have to travel a lot in flight to meet investors or conferences. I mean, the fact that one can have a meeting with someone, you know, virtual meeting with someone in you know, Boston, New York, Chicago, all in the same day is great. And I think everyone has benefited from that.
John Simboli 26:20
What areas of thought leadership in biopharma hold the most interest for you at this point?
Clive Richardson 26:27
I think, in the diseases we're treating, and I think I may have mentioned this earlier, these are very complicated diseases, with lots of different pathways. And one of the challenges for all of us is identifying the right patient target group. So I think the challenge is, you know, you have a disease you're targeting. Now, is that really a single disease or are there a multitude of variants of that disease within it? And are there markers that you can identify that would allow you just to treat a particular target group with more efficiency? And I think that's an area that is exciting and is unquestionably going to grow. And I think I mentioned in TMA, you know, one of the markers there for treatment is elevated C5B9. And you look at things like COVID pneumonias, they can be complicated, really difficult to treat, but some of the treatments might have been more effective if they'd identified subgroups, I think this whole concept of biomarkers, and identifying subgroups of patients that are more amenable to your particular treatment, I think that's a very big area and that will, for these inflammatory diseases, I think that will improve patient outcomes significantly if we could do it correctly. And we're already on that path. So it's not a pipe dream. I think it's something we'll just see a lot more of, in the next five to 10 years.
John Simboli 27:59
When you think back to being at university, and those moments when you were captivated by entering a new intellectual area, I think that happens to many of us. It just, you can't believe how attracted you are to that thing. Do you remember what that was? What that particular aspect was? When you said, I want to study this.
Clive Richardson 28:21
At university? Yeah, well, I studied biology at university. It's not directly relevant to what I do now. But one of my tutors was a guy, I don't know if you know him,, Richard Dawkins, he's, a very famous evolutionary biologist. I found that very exciting. To be honest, you have to have a curiosity. I think that's part of a prerequisite mindset because you've got to be curious because there's a lot of unknowns. So I think the flip side of curiosity is that when you discover something new, it's particularly revelatory. It's a wonderful thing.
John Simboli 28:59
And if I flipped that, in my own mind, the word ambiguity comes to mind. And I think, how does one combine curiosity with the understanding that with it comes ambiguity? Is that is that a difficult thing? Or is that a fun thing as an executive?
Clive Richardson 29:16
I mean, I think ambiguity is obviously a challenge because when you're developing drugs, you're trying to understand what's happening, and that understanding helps you decide on the next path, but clearly, it's ever-present. You have to go forward based on your best guess or your best estimate of what's appropriate. So it's, I think, it's a really great question because, you know, we're only scratching the surface of our understanding in many of these areas. So it's I think it's something you've got to live with and I guess it's potentially a trap, you know, you can get trapped into trying to find the perfect answer for the perfect solution, but that may not be appropriate. But having said that, you know, drug development is also about lifecycle development. So, you know, you get a drug approved, you're treating patients, that doesn't stop you developing a next-generation drug that's better and that I think that's how you have to get around the ambiguity. You're just ever improving in terms of the lifecycle development of your drug or other drugs.
John Simboli 30:24
Thanks for speaking with me today, Clive.
Clive Richardson 30:26
Thank you, John. I really enjoyed that. So thank you.