Latest / The BioHub - by Avetix / Episode 118 - Declan Doogan - CEO & Executive Chairman of Causeway Therapeutics

Transcript

Episode 118 - Declan Doogan - CEO & Executive Chairman of Causeway Therapeutics · The BioHub - by Avetix

0:03
So welcome back to the episode of the Bio Hub.
0:06
Today, we're thrilled to welcome on Declan Dugan, a physician and
0:09
biotech leader with over 30 years experience in the biotech
0:12
industry from senior roles at Pfizer to executive leadership
0:17
at Amarin. And he'd also Co founded Bio
0:19
Haven. Declan's help bring ground
0:21
breaking therapies from concept to reality.
0:24
Now as CEO and Chairman at Causeway Therapeutics, Declan is
0:27
driving innovative micro RNA based treatments for
0:31
musculoskeletal and age-related diseases.
0:34
So join us today as we'll discuss the origin story of
0:37
Causeway and the problems he's trying to solve, the recent
0:40
positive data, as well as entrepreneurship.
0:44
So Declan, thanks so much for coming on.
0:46
How are you? I'm very good, Tom, and it's
0:48
good to be talking to you. Yeah.
0:51
Look, it's a pleasure to have you on.
0:53
So let's let's just start off with your journey through the
0:55
field. So you've had a remarkable
0:57
career across both big pharma as well as biotech.
1:01
What originally drew you into drug development, and how did
1:04
your time at Pfizer shape your approach to innovation and
1:08
leadership? Well, actually none of this was
1:11
planned. It was pure accident.
1:15
I back in the day when I was in clinical medicine in Glasgow, I
1:18
answered a job posting in the British Medical Journal for a
1:22
research position and it turned out to be with a small pharma
1:25
company in Holland. So I'd completed my specialist
1:29
qualifications and took a year out and as I left the medical
1:35
fraternity and my boss did not think it was a great idea.
1:39
They thought pharma was not a legitimate career choice and
1:43
it's certainly not for a young doctor.
1:45
And I would not have a, a good position had I gone back.
1:50
So there was a, a tart of a threat there as I as I left, but
1:54
I was determined and he did have a wee look outside of clinical
1:58
medicine. I did, I did missed it.
2:02
And so I was actually contemplating a move back to
2:05
clinical medicine, but Pfizer hired me to develop what was to
2:09
become Zoloft. And then I got so involved in
2:13
drug development, I stayed for 25 years.
2:17
So that was not planned at all. But it was on the basis of an
2:23
energizing set of circumstances where you're you're not sure
2:29
what's going to happen in a clinical trial.
2:31
And there's a lot of crossed fingers behind your back when
2:35
you are waiting for the results to come out.
2:37
And also there's a lot of failure.
2:41
And I think that's one of the things I, I got out of my time
2:44
with Pfizer, Most of drug development is about failure,
2:51
but then Master success at the same time.
2:55
And I think what I've noticed over the years is that pharma
2:59
drug developments become increasingly sophisticated.
3:03
We have new technology. And when I joined it was the the
3:06
period of the 9th, the 80s and 90s was the the blockbuster
3:11
products were we call pharmacologically based products
3:15
like beta blockers, calcium terminal blockers, SSRI and so
3:19
on. And that led to the burgeoning
3:24
of pharma. It became a bigger and bigger
3:27
commercial force in society. And indeed Pfizer was the same.
3:33
It went from being, I don't know what I'd call a normal skies
3:37
company, but when I went there, it was a company in the UK which
3:43
was of modest proportions. After I moved from Pfizer UK and
3:50
went around the world, I went to Japan and the UUKUSI came back
3:55
to the UK and the, the, the transformation in the Pfizer
4:00
campus was unbelievable. There were massive office to
4:06
labs facilities and there were thousands of people working
4:10
there. And this was the legacy, if you
4:13
will, of the success of 90s and eight 90s and so on drug
4:20
discovery, we had big products, blockbusters and it fueled the
4:24
growth of the company. But then something happened.
4:29
And what happened when I came back in the in the 90s, sorry in
4:35
in the early 2000 was that the work that was done in drug
4:38
discovery in the 90s did not pan out in the way that was hoped.
4:44
We had a lot of drug failure, a lot of missed investments that
4:50
didn't really play out. And it was a time of I suppose,
4:56
you know, thinking what has gone wrong.
4:59
And I suppose this, this was not just a Pfizer thing.
5:02
It was something that really affected the industry and it was
5:07
the biotech revolution. If you look at what products are
5:10
on the market today, the new drugs coming out, there are
5:14
fewer, fewer of them being small molecular entities and most of
5:20
them are biologics. So the science moved on and I
5:24
think that Pfizer didn't move as fast as maybe other companies.
5:29
And so that was a big change. And so that was one of the
5:32
things that struck me that we needed to have more innovative
5:38
risk taking thinking. And that was where I think that
5:43
the staff, the workers in in the labs were perfectly able
5:49
scientifically, but the structure around was not able to
5:53
capitalize on some of that innovative thinking.
5:57
And you, you mentioned then you'd spent almost 25 years at
6:00
Pfizer. I can imagine you could have
6:02
stayed there for the bulk of your career and and lived
6:05
happily ever after. What like what was inspired you
6:08
to take a more entrepreneurial route and start building
6:11
companies from the ground up? I stand critical of Pfizer, but
6:14
I'm not. I'm hugely appreciative of what
6:18
I would call a 25 year apprenticeship.
6:22
Many, many learnings, many experiments and working with
6:26
fantastic colleagues and it was a a wonderful company to be part
6:31
of. But I found as I was getting
6:34
towards the 25 year mark, I suppose I felt that we were too
6:40
industrialized. I thought that was maybe an
6:43
opportunity for smaller, smaller organizations to contribute to
6:50
the future of drug development. And indeed I think that was the
6:54
case because we saw a number of even my Pfizer colleagues
6:59
leaving and going to smaller companies and enjoying a career
7:05
outside of big pharma, which later translated into both
7:09
scientific and indeed financial success.
7:13
I, I was fine just to leave Pfizer and do non drug things.
7:20
But then after about four weeks of leaving Pfizer, I got
7:24
approached by the people at Amarin, could I, you know, help
7:28
out on Amarin R&D and somebody would say like a fool, I said
7:34
yes. So I got involved, got back on
7:37
the horse again, but this was in a very different environment.
7:41
I joined the company and within a few weeks the phase three
7:45
program had failed, more failure.
7:48
And so then it was a time to rethink, was this company going
7:53
to go to the wall or was there anything we could do with the
7:57
science that we already had in in in the company?
8:02
And indeed that was the case. We repurposed the the product
8:07
which turned out to be very successful for a different
8:10
indication. We recapitalized the company.
8:13
We brought it to the US and and actually started in my hometown
8:20
of Connecticut with a small highly focused and very expert
8:26
team. And we took with but a few
8:29
people this product through the FDA and FDA approval for
8:35
hypertriglyceridemia. It started off life being
8:39
studied in Huntington's disease, and the pivot was to
8:43
hypertriglyceridemia. And the learnings from that were
8:48
the science was telling you something.
8:50
And it's about leaps for faith. Leaps of faith are often very,
8:54
very dangerous because you can land badly.
8:58
And in this case, the repurposing of the product was
9:03
based on thorough and rigorous assessment of the science
9:07
evidence based thinking. So that was my first lesson.
9:11
And so I credit the team, the the scientific acumen and also
9:18
investors for for going along with it.
9:21
And so it, it was that I would call it an R&D success.
9:26
And so that sort of got me involved in the the somewhat
9:31
scary world of investment in small startup biotech.
9:36
And OK, the Amarin was a publicly traded company, but it
9:40
was restarting from from scratch almost.
9:44
And so I then joined other boards and and learnt life on
9:50
the outside of big pharma. And that was dynamic and it was
9:56
exciting and it gave me more, I would call it use the word
10:00
agency. I was not as aware as shackled
10:03
to one pair. I could have a broad portfolio
10:07
of partnerships I could engage in.
10:10
So that made a lot of sense for me.
10:12
Just talk us through your current venture, Causeway
10:14
Therapeutics. What were some of the problems
10:17
you and your Co founders were trying to solve and what was the
10:21
inspiration behind the company's mission as well?
10:24
So I want to say about Causeway is Causeway is, but I think I
10:28
would say the third venture after Ameren and and Biohaven as
10:35
a myself being fault in the drug development process 'cause we
10:41
started off with the two inventors of the technology
10:47
which is micro RNA technology in Glasgow.
10:50
This is Neil Miller who is a an orthopedic surgeon and Derek
10:55
Gilchrist who is a molecular biologist.
10:58
And they discovered that tendon disease is associated with a
11:04
loss of a micro RNA called micro RNA 29.
11:10
And this was a, a new world to me.
11:13
I knew nothing about this. So I, I was having to learn
11:16
fast. And why I got involved in it was
11:20
because one, that I come from Glasgow, I went to Glasgow
11:25
University and this was a Glasgow thing.
11:28
And that the the, the quality of the science was excellent.
11:33
But I was able to learn from them that there was a biological
11:40
plausibility to what they were doing.
11:43
They had discovered that this micro RNA, when you had a tender
11:49
tendon injury, it the the micro RNA dropped and that's where
11:55
Derek Gilchrist come in because he created a synthetic
11:59
oligonuclear type analogue of micro RNA 29 that could be
12:05
injected into the tendon and restore the levels of collagen
12:10
1. Collagen 1 is that fiber that is
12:16
stronger than steel that was that gives the tendon its
12:22
strength. What happens when you've got an
12:25
injury? Collagen 1 drops and collagen 3
12:30
comes in to try and keep the tendon integrity.
12:33
The collagen 3 is very, very weak and and it makes for a a
12:38
very dysfunctional tendon by giving the micro RNA 29 the
12:46
synthetic form which is called tanomere.
12:50
This restores the balance and the healing within the tendon.
12:54
Now you could say that's a leap of faith, but they've shown the
12:58
results both in mouse in horses and the phase one study, which
13:05
was used to, to look at safety also showed a signal of
13:10
efficacy. And at that point I, I really
13:14
felt as though they were on to something.
13:17
And we then had to raise the money to, to support a phase, a
13:23
large phase two study in patients with tennis elbow or
13:28
lateral epicondylitis. And we were still a very, very
13:32
small company, but a few people with consultants and, and I led
13:37
the round to raise, you know, the, the funds to support this
13:43
phase two study. We also had survived on grant
13:47
funding as well. So at this point in time, we are
13:52
now the end of the phase two process.
13:56
We have shown excellent results, if I may say so, that the drug
14:02
has performed extremely well in patients with tennis elbow.
14:07
A single injection of this drug, Tanamir into the tendon lesion,
14:13
the tendinopathic lesion, which you can see on ultrasound would
14:18
actually be associated with therapeutic benefit.
14:23
And we showed both pain function and imaging or tendon structure
14:29
improved. And there's nothing else like
14:31
this on the market. And that's what's got me
14:34
particularly excited for Phase 3.
14:36
So we have a unique product occupying a space for which
14:42
there are very little competitors, if any.
14:45
And so we are now, as we're blazing a trail in the tender
14:49
space. That sounds exciting for sure.
14:51
Could you just go into the the data a little bit more and what
14:55
makes your approach to tendon or soft tissue repair different
14:59
from what else is out there? I know you mentioned that
15:01
there's very little competition out there, but like who do you
15:04
look at as companies that are doing something slightly
15:07
different but maybe somewhat similar?
15:10
So I'd love to, I'd love to re offer a list of companies, but
15:14
let me just say what the standard of care is today.
15:17
If you have tennis elbow, you will be offered physiotherapy or
15:24
non steroidal anti inflammatories like ibuprofen.
15:28
That's it. And it sounds ridiculous, but
15:32
I'm sorry, but that's what we've got to offer you.
15:34
And then if that doesn't work, sometimes surgery, that's for
15:38
the elbow. Now we're also looking at the
15:41
shoulder, the shoulder, what we call the, the, the indication
15:45
rotator cuff, which many, many people know about and and
15:50
frankly complain about it. This is about five times the
15:53
market for out for over lateral epicondylitis tennis elbow and
16:01
that is an A condition that often ends up requiring surgery.
16:09
You can use steroids in this situation probably more and you
16:14
can't use steroids with tennis elbow because it causes tennis,
16:18
It causes thinning of the the the tendon.
16:22
They use steroids in rotator cuff.
16:27
They also use other things like stem cells, platelet rich
16:32
plasma, but none of these have been shown to work.
16:37
This is why I think we need to be evidence based on our
16:39
thinking. People are using these
16:42
therapies, frankly, because they don't have much else.
16:45
And our, our goal here is to actually avoid surgery for the
16:50
patients because that is costly and and really impacts their
16:54
life. So we hope that this agent can
16:57
be frankly as I said unique and I don't see any other companies
17:04
out there offering FDA approved medicines or even as as I
17:10
understand it, there isn't much activity in the R&D space.
17:14
So I'm afraid to say there isn't much yet out there and that's
17:18
why Causeway is you have to say a meeting in the fields.
17:22
But look, that's that's exciting.
17:24
The amount of times I hear it from companies where they're in
17:27
such a crowded space. And it's always the case of, you
17:30
know, what's different about what you guys do compared to
17:32
XYZ. So yeah, that's that's amazing
17:35
that that you guys are the the leaders in that space.
17:38
Yes, we also are learning as well.
17:42
We are humble enough to realize what we don't know and with each
17:47
experiment we're learning how to do it better.
17:50
So has there been substantial learnings from the phase two
17:52
study that this does precision guided, in other words that you
17:57
have to be sure that the needle is into the tendon lesion and
18:01
sometimes it didn't work in the phase two study.
18:04
So that's why the patients did not any get any benefit.
18:08
So we're making sure that the way in which the phase three
18:12
program is going to be conducted is by using expert centers where
18:17
we have a high degree of confidence that they know how to
18:21
inject the tendon and then increase the potential for
18:25
therapeutic. You've obviously achieved a lot
18:28
for your career at Pfizer, Amarin, Bio Haven and Nell
18:32
Causeway. Like what's the motivation?
18:35
What keeps you motivated to keep going with all of.
18:38
This well, I suppose a sort of silly answer is I'm not very
18:42
good at golf so so I would have have to find something else.
18:48
The serious answer is it's a an area.
18:51
I mean, I love medicine. I love and activities related to
18:56
medicine and health. My key interests are identifying
19:02
new therapies because they can have such a dramatic effect on
19:06
the health of individuals. I I'm still very strongly
19:10
clinically orientated. I'm, I'm not really a deep
19:13
scientist, but I, I like the diagnostics of medicine.
19:18
I like the helping people come through with new, new medicines
19:24
and also new start-ups. There's another start up in
19:27
Glasgow with a peptide company, peptide disruptor company,
19:31
Company they were trying to incubate and that's where I
19:35
really warm to interacting with young entrepreneurs because
19:41
they're the ones who are going to come up with the innovations
19:44
and with their risk taking, putting their careers on the
19:47
line as Derek Gilchrist has done, that we can get a
19:52
innovation into the therapeutic space, but also we can see these
19:56
drugs emerge and frankly, people can have wonderful careers going
20:01
this route. Rather than just staying in
20:03
academia. So it's a good alternative from
20:06
for them and I think it's something for the UK.
20:09
They need to have more entrepreneurs and they need to,
20:12
if I can see it, they need to listen to people who have gone
20:16
there that way before and have been successful.
20:19
Just on entrepreneurship, what would you advise be for younger
20:23
founders or scientists listening who were thinking of taking an
20:27
early stage idea and turn it into a viable biotech company?
20:31
What What would you what advice would you give to people who are
20:35
wanting to take that leap one day?
20:37
Do it. And I think that that is that is
20:41
for young people often they they don't have the same as it were
20:46
financial encumbrances. They don't have the families,
20:52
they don't have the financial obligations.
20:55
They have maybe even geographic flexibility.
20:59
I think I would encourage young scientists in this case to think
21:05
about where their career is in a way that I never did.
21:09
I just stumbled into things and I didn't have a mentor.
21:14
I, I would like to think that people coming through the
21:17
university system have got a mentor who could provide
21:21
constructive input to them in their career choices, rather
21:26
than, well, you must do a PhD and then hopefully get a, a
21:29
senior position in academia. Open, open the, the, the, the
21:33
landscape up and say, these are the different opportunities.
21:37
And again, I go back to the young scientists finding
21:44
opportunities, leveraging their scientific knowledge.
21:48
What could they do with that scientific knowledge?
21:51
Have they actually come up with some new findings that could be
21:55
translated into meaningful, in this case, therapeutic agents?
22:01
And then take that idea and either speak to their bosses,
22:05
but also speak to people outside the university and say could I
22:10
do something with this? So again, I would encourage
22:13
university to create a milieu whereby young innovative
22:19
individuals could see a way to getting support, guidance,
22:23
mentorship and confidence building that they could do
22:27
this. I think it's something that's
22:29
incredibly important for Britain do.
22:31
You think that there's been a or do you think like this, this new
22:35
generation maybe lapsed that entrepreneurial mindset?
22:38
Do you think there's been a shift from how people see
22:40
entrepreneurial entrepreneurship now?
22:43
I don't know. I mean, I, I was there when I
22:45
was growing up have to been in clinical medicine, the, the
22:50
constant, the word entrepreneurship you reserve for
22:53
industrialists and bankers and so on, not from medics and
22:59
scientists, but I think over time, I think that people have
23:03
validated the, the choice of eggling into pharma.
23:07
And so pharma is in its broader sense of the, the, the word like
23:12
biotech and and large pharma, small startup world and so on.
23:18
It can accommodate a a large range of individuals, different
23:22
phenotypes. But what I would say is that
23:26
it's tough, but take the risks when you're young, not when
23:31
you've got three kids that the university you're trying to
23:35
support, the mortgages and whatnot.
23:37
Take it when you're younger and get on the roads.
23:40
And if it doesn't work, is it a way back to something else?
23:45
Is somebody sawing off the, the, the branch behind you?
23:50
Or are you confident enough that, you know, I have a skill
23:53
set that I can leverage? I can, you know, take a chance.
23:58
If it doesn't work, I could do something else.
24:01
It's that mentality now. Is that different today?
24:04
I'm not sure. I'm not close enough to be able
24:07
to provide sensible commentary, but I just know what I'd like to
24:11
see. And just like looking what's
24:14
next for Causeway, like beyond your lead program, what are like
24:18
the sort of next major milestones and advancements that
24:21
you're most excited about? So we're raising money for the
24:25
phase three program both in tennis elbow and also for
24:31
rotator cuff. So we want to raise a large
24:34
amount of money to become a bigger full development
24:39
enterprise. We will increase our geographic
24:42
footprint both in in from Europe into to the US and we will be
24:50
looking for partnerships to help us in this.
24:53
But Derek Gilchrist is also our chief scientist and is the
24:58
discoverer developer of new ideas.
25:02
And we have other approaches in cardiovascular medicine,
25:07
dermatology and other areas that we're not concentrating on just
25:12
now because we want to deliver 10 Amir.
25:15
But there is a a a vast array of possibilities for Causeway and
25:21
that gets me excited. The the the RNA technology which
25:25
is micro RNA messenger RNA, micro RNA technology has really
25:31
got big achieving a place in in therapeutic research.
25:37
Nice. And just to to finish off, this
25:39
is a question that we always ask for people that come on the
25:43
podcast. But if you were to have any
25:45
dinner with any free people, past or present, who would you
25:49
go for an and why? Well, I'm, I'm Tom, I'm glad you
25:54
gave me some warning, warning of that.
25:55
And so I could at least think about it a wee bit.
25:59
And the three people that I thought of right at the
26:02
beginning after I had this question are Leonardo da Vinci.
26:08
Some people would call him a cool dude, but I mean, this is
26:11
an amazing mind. What this person did was
26:14
unbelievable. Sculptor, architect, engineer,
26:18
scientist. And he also forayed into feels
26:23
like anatomy and and and zoology and so on.
26:27
To be able to talk to him. Let's leave the language a bit
26:30
out, but to be able to talk to him and hear what kind of
26:34
individually was why he thought the way he did would be a
26:38
remarkable opportunity. The other one near to home would
26:45
be Andrew Carnegie. I read his his biography and a
26:50
remarkable man, modest circumstances coming from
26:55
Scotland and he moved to the US where he found massive fame and
27:00
fortune in in steel and and heavy industrials at the time.
27:08
So he would be up there with the Rockefellers and so on.
27:13
But what really impressed me was he gave 90% of his wealth away
27:19
and his his impact is still there today with the libraries,
27:23
the Carnegie Fellowship and so on.
27:26
So why, why is he a role model for today's entrepreneurs?
27:33
Would he do it again? If this way, knowing what he
27:37
what he's done and the effects of his philanthropy, I would be
27:42
really, you know, delighted to speak with him.
27:46
And the last one is a simple one.
27:48
It's I'd like to have dinner with my great grandfather.
27:52
I didn't know my grandfather and I certainly wasn't going to know
27:56
my great grandfather, who he was a small subsistence farmer in
28:01
Donegal in Ireland. And he would have lived through
28:04
the famine and he was raising a family on a small pot patch of
28:10
not very fertile ground. But I would love to speak with
28:14
him and say this is what one part of the family has become.
28:19
What do you think of that? To just sort of bridge the years
28:24
from his origins to what we're doing today in this very, very
28:29
complex world? I would find that fascinating
28:32
and certainly if my great, great grandchildren could talk with
28:37
me, would be amazing to hear what they were up to.
28:40
Well, look, 3 great, great answers there.
28:42
And it sounds exciting what you're building at Causeway as
28:45
well. I'm sure, no doubt it'll be a
28:47
success just given what you've done for your career already.
28:50
So yeah, look, thanks again for coming on and helping us out
28:54
with this. It was a pleasure.
28:55
And yeah, I look forward to to following the progress going.
28:58
Forward Well, Tom, thank you. Thanks for the opportunity and
29:02
for the work you do in getting these stories out and and
29:06
helping people understand the world.
29:09
So thank you.