Latest / The BioHub - by Avetix / Episode 112 - Rodolphe Clerval - CEO of Coave Therapeutics

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Episode 112 - Rodolphe Clerval - CEO of Coave Therapeutics · The BioHub - by Avetix

0:06
So welcome back to another episode of the Biohub podcast
0:09
and Avetics Podcast. Today I'm joined by Rodolf
0:13
Clavell, CEO of Co Therapeutics, a company redefining targeted
0:18
gene therapy. Rodolf has one of the most
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unique backgrounds in biotech. He started in biochemical
0:24
engineering, moved into investment banking, became a
0:27
sell side analyst, then joined Enzyme, then helped build enter
0:31
Rome into a major partnering success.
0:34
And now he leads Cove for a bold pivot into precision gene
0:37
therapy. In this conversation, we talk
0:40
about that journey. We talk about Co transformation,
0:44
why their technology is generating so much excitement
0:47
and the mindset it takes to lead in this industry.
0:50
So let's get into it. How are you right off?
0:54
I'm, I'm doing well. Thank you Max for having me.
0:57
Very happy to, to have this conversation.
1:00
No. I'm going to say, but it's it's
1:02
really a pleasure to have you on.
1:04
Let's just start with that unconventional journey that I
1:07
was just talking about, you know, starting in science, then
1:10
finance and equity research, then into BD and now CEO.
1:15
What what drove the pivot originally from the lab into the
1:19
financial world? While I guess it was, it was
1:23
somewhat opportunistic, but they're so built on some
1:27
constant interest to what science can generate in term of,
1:33
you know, something useful for for people.
1:36
So I, I was really trained like a biochemist, microbiologist
1:41
that was very deeply involved in science and, and bio
1:46
manufacturing. And we were back to the end of
1:48
the 90s. So it was the very beginning of
1:51
the first therapeutic proteins being commercial in the market.
1:55
I remember seeing advertised from Amgen and Genentech on, on
2:01
nature, you know, claiming they have the first, you know, EPO
2:06
product manufacturer. I, I, I thought it was
2:10
fascinating because I was a in, in depth in the biology and the
2:15
fact that we can produce diabetic protein was something
2:18
as far as I'm very exciting for me.
2:19
But I was seeing me as a, as a someone, you know, participating
2:24
to the science to, you know, developing processes for this.
2:28
And, and when I completed my, my, my, my university at, at the
2:36
ETH in, in Zurich in Switzerland, I, I was a very
2:40
different environment in the sense that a lot of, of the
2:44
people around me were a, you know, finishing their PhD
2:50
postdoc and they were moving to either creating company or
2:53
moving to investment banking, which no, Zurich was a Austin is
2:58
a very important financial place.
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And I was like, wow, interesting.
3:01
Maybe we can do something other than working on the bench.
3:04
And, and you know, I just applied for a few positions.
3:09
Initially, I thought I would work with venture capitalist
3:12
firm. And finally, my, my, my CBE
3:16
moved to an investment bank group that were looking for
3:20
specialized people in in the field.
3:23
So I was really I jumped littering a word that was an
3:28
unknown word for me. I didn't know what was a, a, a
3:32
an IPOI didn't know what was the equity market.
3:35
I'd never been to a trading floor and I from one day I was
3:40
at the labs in the in Zurich. The day after I was in the
3:44
trading floor in Paris downtown. So it was a huge hedgehog for
3:48
me, to be honest. When I arrived there, I but, but
3:52
you know that that was a mix of opportunity, but also, you know,
3:57
these constant interest to to see the science materialise in
4:02
in something credible, concrete. Yeah.
4:07
I mean, I love the boldness of it as well.
4:09
You know, when we were talking, when we met Jeffries, you were
4:12
talking about that, that pivot and why he did it.
4:17
Just talking about your investment banking and equity
4:21
analysis days, It it probably gave you a really unique lens
4:26
on, on biotech. What?
4:28
What did that time teach you about how companies succeed or
4:32
how they fail? It, it was, it was a fantastic
4:38
time to rapidly learn how a company can develop a product
4:46
from from scratch from, you know, a university to started to
4:53
a larger biotech to a pharma because we were as a cell sign
4:57
and as you are really overseeing what those companies are doing.
5:02
And, and very quickly I work in a team where my role was
5:07
focusing on, on novel therapeutic approaches like
5:11
serozine kinase inhibitors, antibody.
5:14
You know, we were early in 2000 and one 2002 long time ago, but
5:18
it was the very beginning of Avastin in oncology.
5:21
It was the beginning of of of all the product from Genentech
5:26
and Rush in, in in targeted oncology.
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So I was doing a still a lot of actually science work in, but
5:35
more reviewing pipelines, understanding, you know, what
5:40
will be the journey from, from early preclinical to a phase
5:44
two, where, where in this whole process, the, the, the value
5:49
creation, my stone and, and I really rapidly, I've seen this
5:56
old journey from, from, from discovery to value creations.
6:02
And, and that was great because I would say if I would stay in
6:07
the industry, it would have taken me 15 years to understand
6:09
this whole value chain. And, and, and so that was a
6:13
fantastic. At the same time, of course,
6:15
I've been trained in parallel in, in corporate finance, which
6:19
was really useful to understand all the, you know, the mechanism
6:22
behind financing a company from, from the private side to the
6:26
public side. So you know, very, very
6:29
interesting positions. And, and of course, what was
6:33
fantastic is to be very close and so often, often very rapidly
6:39
facing key executives in, in big farmers and biotechs.
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So I've got memorable experience there.
6:47
Yeah, I I think it's a great start to life in in the industry
6:53
and, and pretty interesting at that.
6:55
And I also just want to talk about COV.
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You know, the company has been through a major evolution,
7:02
including a name change, pivoting strategy and focus.
7:07
What What's the story behind the transition?
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So. Cove no has quite a long
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history. I I joined the company in 2020
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and the company was already up and running for the for four
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years when I joined the company as a second CEO and the company
7:22
had the different name. The the previous name of Co was
7:26
Horama. It was a company created back in
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2016 on on the model of of Spark, which was one of the icon
7:36
company in gene therapy. So it was a single asset gene
7:41
company, gene therapy companies focusing on one ultra rare
7:45
disease on on back in 2016, eighteen those days, this kind
7:51
of company was highly considered by the pharma industry.
7:56
But but things changed quite dramatically starting in 2021
8:00
when people realized that ultra orphan disease gene therapy
8:04
development will take probably more money to get to a certain
8:09
value infections, but also in term of of, you know, commercial
8:14
opportunity. So we start to see big Pharma
8:18
withdrawing from the field of your trial rare disease, doing
8:22
more rare or not so rare disease.
8:25
And and when I joined this company basically my mission was
8:30
a completing the clinical development of the lead asset
8:33
that we did, finding a way of finding a partner to this asset.
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So we license out in 21 this asset to a mid sized pharma that
8:42
took care of it. And I spent out this asset from
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the company just to refocus the company on what it is now a key
8:52
platform for delivering genetic payload and developing new
8:57
therapic therapic program using this platform.
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So that's when in in between 22, we decided to switch the name
9:04
from Orama to Co and the name calls White Susan because we our
9:10
platform which is, which is based on a traditional AV
9:14
backbone. What we do is we transform this
9:17
AV backbone by conjugating, targeting moiety at the surface.
9:23
It's basically decorating those a VS with specific ligands and
9:27
it's we call that conjugation. It's like antibody drug
9:29
conjugate. We do AV ligand conjugate, so we
9:33
conjugate AV. So we name the company.
9:36
COA VE. COAVE Cove, because this is our
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core platform, this is how we have transformed the company and
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and it was, you know, a mixed of the history of the company.
9:47
We have built a lot of expertise in, in in gene therapy basically
9:52
and that was core. We spun off the historical
9:56
program, restart the company on the platform and we raised in in
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early twenty €532,000,000 round to remove the company from the
10:07
platform to the pipeline development.
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That's amazing. I think, yeah, it's not an easy
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task that fundraising in in the current market as well.
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So congratulations. Thank you.
10:21
Let's just talk about that, that platform a little bit more as
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well because like you said, it really does define the company
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and it is genuinely novel. What makes the technology so
10:32
exciting and what problem are you solving better than than
10:36
anyone else in the market? A VS which are viral vectors for
10:42
gene therapy remain the the most used vectors.
10:45
If you look at all the commercial product or end state
10:48
or late stage development product they are based on a VS.
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But we know those A VS has a lot of limitations, especially
10:56
tissue specificity and and safety, which goes along when we
11:01
inject the Navy in in a human body, it goes massively to the
11:06
liver. That is well known.
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So if you target liver disease, you don't have delivery issue.
11:11
When you want to target other tissues by a non invasive
11:14
manner, you face a lot of issues.
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If you face that you need to have a high dose of the product
11:20
to reach the other tissue and then it leads to systemic
11:24
toxicity. So there's, you know, many
11:26
stories about that. So what happened?
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We, we knew the field knew this. These situations for the last 15
11:34
years, people have tried to improve AV by creating actually
11:38
artificially variant of AV vector.
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It's what we call the directed evolution approach.
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They basically generate millions of new AV vectors randomly and
11:50
they inject in animals and try to identify the one that would
11:54
go to a certain tissue. It has proven to work in
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primate, it has not proven yet to be translatable to human
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because the issue with this technology is you have a bias in
12:08
selecting a certain vectors for a certain animal space species.
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So that's that's the one issue. We do the other way around.
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What we do is, is instead of generating randomly something,
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we first look at what are the key receptors on certain tissue
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we want to target. And from those receptors we
12:34
basically screen small molecule ligands that are rationally
12:39
designed to target this human receptors.
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And when we have the right ligands, we use our conjugation
12:46
technology to decorate any kind of AV serotype, any kind of AV
12:52
variations we can find. So it's a much more efficient
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because it's, it's first based on human biology, much more
13:00
efficient way to target the tissue, a much more rapid way to
13:05
generate a new AV candidate because screening small
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molecules is always much faster than screening millions of of AV
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variants. And then in a matter of, of
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actually a year, we can define and find a good candidate.
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And this is what we have done on three different tissues, the
13:24
eye, the brain and, and the muscle using our technology and,
13:30
and, and we have also with the technology the opportunity to
13:33
completely detarget the liver. So we've now having enhanced
13:39
vectors that have these unique properties, which are the, the
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actually there's three key key properties we need to have for
13:47
new vectors, new generations. One, they target the right
13:51
tissue through a known receptors and a known mechanism be the the
13:57
need to be the targeted of the liver, but truly the targeted.
14:00
So nothing is going to the liver.
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And the third very important features is those AV are a can
14:09
evade the immune system. So they are not you know they're
14:14
they can basically the antibody that naturally recognize AV are
14:19
not able to recognize all victor because of this the presence of
14:23
the ligands at the surface. And let, I mean, let's just talk
14:27
about specifically your lead program as well, which is pretty
14:31
exciting and aiming to change the game in retinal vascular
14:34
diseases. What, what, what should people
14:37
know about the opportunity that you guys have here?
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Sure. So this is one of the few
14:44
therapeutic disease which is a career very prevalent disease.
14:48
We are talking about weight age-related macular
14:51
degenerations and diabetic macular edema.
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So they are very, very frequent disease.
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That basically the way those disease develop is you have
15:02
another growth of vascular of of blood vessel in the retina, the
15:08
back of the eye. And the, the growth of those
15:12
vessels leads to destructions of the key cells of the back of the
15:17
eyes of photoreceptors. The, the mechanism behind this
15:22
disease is extremely well known and there's drugs that works in
15:27
preventing the growth of those blood vessels.
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Those drugs are anti via GF drugs.
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They are antibodies and and there's actually four different
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antibodies that have been developed all targeting the same
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mechanism that have been approved in the market for the
15:46
last 15 years. And it's a huge market.
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We are talking about 16 billion sales market.
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And, and so the question that you should ask is why you guys
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are going there? And the drugs that works and,
15:59
and indeed drugs works until you get, or you, you treat the
16:05
patients frequently because this is drug that you have to inject
16:10
in the eye of the patients every month or every two months.
16:14
And if you start missing injections or you start actually
16:19
increasing the interval between two injections or you stop the
16:23
treatment, the disease will get back in and, and it's, it's
16:27
irreversible. You will lose your visions.
16:30
And this is what happened. Actually, when we look at the
16:33
real world data that have been produced over the last 3-4 years
16:38
by the the whole academic community, we see that while
16:44
those patients with the current drugs benefit from the treatment
16:48
that you're 1 and 2, after 3-4 years they get back to where
16:52
they were before the treatment. So there's a huge medical need
16:56
to have a drug that works but with a very limited number of
17:02
injections and gene therapy is the only options where you can
17:07
have a true 1 injection and done.
17:10
So what we do, and this is not something new because other
17:14
companies are already developing gene therapy in this field, is
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we use gene therapy to deliver the gene and coding for this
17:22
antibody that will block the growth of blood vessels.
17:28
The competitors are head of us. They are now three of them
17:33
entering phase three. They have a product that have
17:37
demonstrated efficacy, some durability.
17:42
So basically when we what we see with this product is they give
17:46
that product once and the patient reduce the number of
17:50
injections, but not to zero. They, those patients still need
17:54
again, what you call rescue injections from the standard of
17:58
care treatment, which is quite a a disappointment for physicians
18:02
because they expect to gene therapy that you inject once and
18:05
it works and, and they are not yet there.
18:08
But the main issue with this treatment is the required
18:12
intensive steroid treatment to contain the inflammations in
18:17
that is, is actually induced by by gene therapy.
18:22
And, and that is a super important limitations.
18:25
We have done multiple discussions with, with
18:29
physicians. They, they basically what we see
18:32
these drugs would probably be used in a limited number of
18:36
patients that are really most severe patients that have no
18:41
alternative to go unless they go to to, to gene therapy.
18:46
So on our side, what we do using our technology of of delivery
18:51
using this technology where we conjugate specific ligands, we
18:55
have developed a unique capsid and a unique vector that go
19:00
exactly to the back of the eye by the route of administrations
19:06
that do not trigger inflammations.
19:09
So we have a much better therapeutic index in term of
19:13
where we put the the anti VIGF treatment and and and the fact
19:18
that we will not need to treat the patients with what what is
19:23
currently the case five months of steroid treatment.
19:26
So we are developing a best in class in this new class of gene
19:31
therapy. This is where we are and we have
19:34
now primate data supporting this role rational, a better
19:38
targeting, better efficacy while a much better safety profile.
19:43
And we expect to enter a new man with this program in in early
19:47
2027. That, that was my next question.
19:51
What, what next and where are we going as a company?
19:54
What, what, what's like the, the big picture goal for you guys?
19:57
Like where? Where do you see the main
19:59
milestones coming from in the next three years?
20:01
So we are so next year's 26 will have additional a primate
20:07
studies to prepare the whole Ind and and CTA package.
20:11
So basically the key studies that will the GIP talks that we
20:16
you know, confirm this, that confirm the the safety profile
20:20
we have already seen in previous studies.
20:23
So 26 will be major a year for you for us.
20:26
And, and starting mid first half of 27, we're going to have our
20:31
first clinical trial, which would be a dose ranging and,
20:35
and, and a dose escalation studies plus an additional
20:41
follow up of patients to be done in roughly 30 patients.
20:46
And, and the final phase 2B data will start later in N of 28.
20:53
So we see generations of key clinical data are expected N of
20:59
27 early 28. And this is the, you know, the
21:03
important data we hope to to to generate them and, and show
21:07
where we cannot confirm our product is, is positioned to be
21:12
the gene therapy that could be, you know, could replace what the
21:17
current biologics are doing on the market.
21:20
And I want to just completely change the topic a little bit
21:22
here because when we first met in well, in London at Jeffrey's
21:26
week, what really hit me about you was, was your mentality and
21:31
your mindset for the industry. I think we were talking about
21:34
interim and how something can happen there.
21:38
And then, you know, you just like, OK, well, how do we deal
21:40
with it? What's the next thing?
21:42
You know? And I just thought that was
21:43
super impressive. And especially, you know, early
21:47
stage biotech, you know, you need a resilient speed
21:50
conviction. What?
21:53
What do you believe is essential in a mindset for leading and
21:59
surviving in a small biotech? That's it's a good question.
22:02
Actually. There's this few things that
22:04
that's important. I think from, from my previous
22:09
experience and my my current experience with Co.
22:14
I think when you build a company and, and when you are, you know,
22:20
setting this idea and, and you stick to it, you have to be sure
22:24
that your idea is built around your understanding of the
22:28
patient needs that that's critical.
22:30
I mean, very interesting. This yesterday evening, I was
22:33
one of the, I was at the General Assembly meeting from one of my
22:37
investors and I met with someone who is the fundraiser of one of
22:42
the largest private equity firm in France.
22:46
And it's a person that has no clue about about science,
22:50
biology and, and, and she, she was teasing me about my pitch.
22:55
And I, I simply tell her, look, what we are doing is there's
23:00
this disease, a white MD and most of the people know about
23:04
white MD because they're pregnant.
23:06
There's a drug that works, but you need to take it every month.
23:12
It's not sustainable. Now we're going to do a one and
23:14
done and, and, and say, look, this is exactly what what people
23:18
need to understand. There's done how you address the
23:22
patient issue and, and, and, and really, and and I'm not the
23:25
first one saying this. When you understand exactly what
23:29
you're going to bring to the patients, then you build your
23:32
whole story and you stick to it. And and that is critical.
23:35
That is, is very important. The second important I guess
23:40
elements on all, all this journey over the last three
23:43
years is resilience. We have been through an up and
23:46
down like any Co in the field. And I think it was even worse
23:50
in, in, in, in the genetic medicine and gene therapy
23:53
because we have seen large pharma company exiting the field
23:58
some unfortunately still a lot of them still investing
24:02
massively. We have seen investors being
24:04
more, you know, questioning. I saw the gene therapy model,
24:08
but still we have investors that invest in it.
24:11
So you have to be resilient. You have to, I mean, when, when
24:14
we, we have hit low, I mean mid 24, to make it very clear, we
24:20
were raising this, this round that we close in, in, in, in, in
24:24
January 25 and mid 24, almost everything was ready to close
24:29
the fundraising. And we got one lead investors
24:32
that for actually reason that was not anticipated, decided to,
24:39
to, to, to give up and, and, and to, to move away.
24:43
And it was absolutely not because of course, it was
24:45
because these investors, the, the one of the men partner
24:50
resigned and, and, and, and moved to another firm.
24:54
And well, it's something that happened.
24:56
So we were like back in September, like unsure we're
25:00
going to close this deal. So this is where you have to
25:04
have first to be can and resilient to have a team that is
25:10
prepared to this because not anyone is prepared to this
25:14
roller coaster. You know, you have people, I
25:17
guess when you when you come from large company where it's
25:21
more stable life you you you don't know what you're going to
25:27
encounter when you're moving biotech.
25:30
So I was lucky that I've been in previous biotech and we've
25:33
hunter home. I've been there for 10 years.
25:36
We, we raise more than 100,000,000, but we have got
25:39
also up and downs in the company.
25:41
So I've, I've been, I've faced that situation.
25:44
So resilience is key. If you are not resilient,
25:48
biotech is not for you. Definitely this is this is a key
25:52
resilience and and very long term vision driven by patients,
25:58
patients need. Yeah, I think you touched on a
26:01
on a bunch of things that are definitely, definitely true,
26:04
especially in the the earliest stage biotech, especially in
26:09
this market, right. So, yeah, thank you so much for
26:13
that. And we're just going to the last
26:14
question right off, which is a question I ask every guest who
26:17
comes from the podcast. So if you could have dinner with
26:20
any scientist or innovator, past or present, who would it be and
26:24
why? I'm projecting rather which
26:28
people are still alive. I would say no.
26:32
The the person I think about, it's actually Emmanuel
26:35
Charpentier. So Emmanuel Charpentier is one
26:38
of the three recipient of the Nobel Prize for the CRISPR, a
26:44
gene editing invention. She she was with Jennifer Dudna
26:50
receiving this Nobel Prize. I think it was, it was not this
26:55
decision. It was well, or maybe two years
26:58
ago and, and, and why Emmanuel? I don't know her personally.
27:05
First of all, I would love to, to have a, a dinner with, with
27:09
her because among all those people, she, she was exposed,
27:13
but she was not the one most on the spotlight.
27:17
She's still an academic scientist.
27:20
So she has a very interesting journey.
27:21
She's a she's French or maybe that's that's something
27:25
interesting. If I have dinner, it's, it's,
27:28
it's always great to, to, to have it in French, but but no,
27:33
this, these apart, she has a very interesting journey.
27:38
She he, he was, she come from the middle class in France.
27:42
She did her oral university in in France.
27:46
She was at Astitut Pasteur, which is one of the most amazing
27:52
institutions for science. And then she moved to, she moved
27:56
abroad to, to, you know, to do our postdoc.
27:59
And then she, she moved in, in, in, in, in Germany and, and in
28:05
other countries. She did a fantastic work and,
28:08
and she discovered CRISPR. So he's old genre.
28:10
And she's, you know, she's, she's not, she's at, I think
28:14
she's still young. I mean that that's an amazing
28:17
scientist and, and still continuing our work in, in the
28:22
field. So I would, I would love to
28:23
understand and spend time with her to understand her, the
28:27
driver and how she, you know, she has been able to accomplish
28:32
this whole journey, which is amazing.
28:34
I mean, absolutely incredible. I mean, as a team.
28:36
But then, yeah, I I completely agree.
28:39
I like that you went down the French route.
28:40
I was just thinking about the the other French guests that
28:43
we've had on the podcast as well, which have gone down
28:46
really well, by the way. Then we had Mark Garrido and
28:49
Phillip Shambarn and now Rodolf. Look, it was an absolute
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pleasure to have you on. I've really enjoyed it.
28:54
It's been really interesting and and thank you so much.
28:57
Thank you for your time, Max. It was a pleasure to to to to
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talk with you today. Likewise, and everyone please
29:04
like and subscribe to the Bio Hub and of Ethics podcast and
29:07
and thank you so much again, Rodolf.
29:09
Thank you.