Latest / The BioHub - by Avetix / Episode 198 - Andrew Obenshain - CEO Inventiva

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Episode 198 - Andrew Obenshain - CEO Inventiva · The BioHub - by Avetix

0:06
So welcome back to another episode of the Biohub and Avetix
0:09
podcasts. Today I'm joined by Andrew
0:12
Obenshane, CEO of Inventiva. Andrew brings more than 20 years
0:16
of global experience across drug development, regulatory strategy
0:20
and commercialization, having worked across the US and Europe.
0:24
Before joining Inventiva, he was the CEO of Bluebird Bio, where
0:28
he led the company's transition into a commercial stage gene
0:31
therapy business. Inventiva is a late stage
0:34
clinical company focused on developing therapies for
0:36
metabolic diseases with its lead program targeting Mash currently
0:40
in phase three. In this conversation, we talk
0:43
about Andrew's journey, the French biotech ecosystem, the
0:47
challenges of leading a late stage company, and what's next
0:50
for Inventiva. Pleasure to have you.
0:52
How are you, Andrew? Very well Max, thanks for having
0:55
me on. No, honestly, honour, really.
0:58
Great to have you. I want to start with you and
1:01
your background. You've had a a very
1:04
international career across the US and Europe and you've now LED
1:09
multiple French biotech companies.
1:12
How did all that journey come together?
1:15
Yeah, well, you would think that when I was coming into college I
1:18
had a degree in genetics and a minor in French, so you would
1:22
think it was preordained. It definitely was not.
1:26
I did have a upbringing that was fairly global.
1:30
I spent half my childhood in Brussels, in London then and
1:34
then half in New York, Connecticut and Chicago.
1:37
So it's transatlantic upbringing and I think that really
1:40
influenced me going forward. I never knew, I never wanted to
1:45
be a doctor. I hate the sight of blood.
1:47
But I went through undergrad thinking I was going to be an
1:50
economics major, just loved my biology courses and genetics,
1:53
and ended up as a biology major that had failed utterly in the
1:59
lab. I had to say we were
2:01
experimenting with crayfish and I was in a neurobiology lab and
2:04
I committed crayfish genocide without any results and was a
2:08
little lost after college as to what to do.
2:10
But thankfully found a route that brought me into biotech
2:13
consulting and I discovered that, hey, I've got this, this
2:16
this whole field of biotech that is that requires all kinds of
2:20
skill sets, not just pH DS and M DS, but MBA, which I eventually
2:24
got and actually ended up going through consulting and biotech
2:29
to venture capital biotech. Then went to Business School and
2:33
combined those three wonderful experiences to become a primary
2:36
care sales Rep for Merck and drove around a Ford Taurus with,
2:42
you know, basically sampling drugs out of the trunk of my
2:44
car. But that was actually probably
2:45
the best job experience I had was what really set me on the
2:48
path to where I am today to really understand the sales and
2:51
marketing and operations of pharma, biotech companies.
2:55
So that's how. And then the international
2:57
component came fortuitously when I was working for Genzyme and we
3:01
were acquired by Santa Fe and I thought this was his, I spoke a
3:04
little bit of French. This was a great opportunity to
3:06
go back over to Europe and thus began a, a career where I was at
3:11
Santa Fe for a number of years in, in France, followed by Shire
3:15
and then followed by Bluebird, all three jobs in Europe.
3:18
And so that's how I, that's how I somewhat ended up in the, in
3:21
the marrying my biotech interest within an international
3:25
interest. And now I'm the CEO of an
3:27
Imitiva French biotech company. Yeah, it's cool.
3:32
Is this your 4th French team that you've now LED?
3:35
I think. It is so when I when Genzyme was
3:39
acquired by Santa Fe, I came, I ran AI, was the chief of staff
3:45
for the COO, but I had a team reporting me as well, OCFPNA and
3:49
HR. So that was my first team and
3:51
then I left Santa Fe to become the general manager of Shire in
3:55
France. And that was a much, much larger
3:56
team. So I ran the French affiliate
3:58
for Shire. You can tell from my American
4:00
accent, I am I, you know, I, although I have an American
4:04
accent, I do speak French. I actually ran that team in
4:07
French. And then I went from Shire to be
4:10
the head of Europe for Bluebird Bio.
4:13
And that job started in France and then took me to Switzerland
4:16
to, to Zurich area. But I still, I built up the head
4:20
of the European team for Bluebird.
4:21
I also built up a French team again as well and then went back
4:25
to the States for a number of years and we became the CEO of
4:29
Bluebird and now I'm back as the CEO of Inventiva in Inventiva's
4:34
base in Dijon. Also that's my my 4th French
4:37
team that I've run overall. I love that.
4:40
What? What is it about the French
4:42
biotech ecosystem which keeps bringing you back?
4:46
Well, the, there's fantastic talent in French.
4:49
I mean, the, the French education system, the
4:50
engineering abilities in France, the, the, the education system
4:55
is excellent. So you have a very, very well
4:57
trained population specifically on the sciences.
5:02
I do love the French culture as well.
5:04
I think it's a, it's a one that that very much values academics
5:09
and, and accomplishment. And you know, France has a
5:13
number of a very, very good training grounds.
5:14
Santa Fe I would name as one. There's another bunch of other
5:17
French pharmaceutical companies. And now you're starting to see
5:20
France really have some successful biotech companies
5:22
appointed Abavax recently and the biotech ecosystems coming up
5:26
now as well. So you do have a wonderful
5:29
talent base in France to start with.
5:32
And very, I can pair that with a lot of international experience
5:36
and you get some really talented people in France.
5:40
Yeah. I mean, we've seen that first
5:42
hand on on the podcast, we've had companies like ABI, VAX Co
5:46
Therapeutics, EG 427 that have all come on and and said really
5:50
similar things. There's a bit of a discussion
5:54
now around Europe and and France specifically about competing
5:59
globally in in biotech. What what do you think needs to
6:02
happen for that really to accelerate?
6:05
So the I mean the science part is not the problem.
6:07
I mean one of the so a Bluebird actually little known fact that
6:11
Bluebird was actually originally the IP all came from France.
6:14
So the in license of the sickle cell program, the adrenoleuka
6:18
dystrophy program, Bluebird had three rare disease programs and
6:22
the beta thalassemia all came from France.
6:24
And that was because in 1999 in the US, it was 1999 right around
6:30
there, the Jesse Gelsinger was a patient on a gene therapy trial
6:35
in the US and unfortunately passed away due to the side
6:37
effects of the gene therapy. And the US put a moratorium on
6:42
gene therapy research, effective moratorium.
6:44
But France actually continued. So a lot of the innovation
6:48
actually happened in Europe. And then it was that IP that was
6:53
taken out and actually formed Genetics, which was the original
6:57
company that then got rebranded to Bluebird.
7:00
And now Ironic is back to Genetics as well.
7:02
But it was actually French innovation that started that.
7:05
And that's really common. The, the, the amount of
7:08
innovation that happens in France, the basic research, the
7:10
translational research, the first clinical trials is very,
7:14
very robust. Where you see the, where you see
7:19
the, the, the lag is a lot of that French innovation that goes
7:22
international. The main market is in the US.
7:25
So when people say that the the French biotech market's
7:29
undeveloped, they're really not taught.
7:31
It's it's not really a fair, fair characterization.
7:35
The early stages of biotech are very well developed in France.
7:39
The excellent research in the hospitals, excellent research
7:43
and actually some government funded research as well is the
7:46
translation into commercial entities that tends to happen
7:49
outside of France. And we can go into a number of
7:52
reasons for that. And the way that a lot of the,
7:55
the way a lot of the kind of the corporate governance is
7:58
structured, the incentives for employees really it's really
8:01
hard to give equity in France to employees that's compared to the
8:05
US. So the equity incentives are
8:06
much, much higher in other countries than in France.
8:11
But the core there, the, the talent that's there, the
8:14
innovation, the science is all there in France.
8:17
And I think you're starting to see that finally translate with
8:19
Abavash, with Infantiva, with othercompaniesaswell.com and DBV
8:24
Therapeutics. Like we could go on.
8:26
There's a number of companies that are really making a go of
8:28
it now in France. Yeah, yeah, you definitely see
8:31
that. You definitely see that.
8:34
Yeah, I want to move it on a little bit.
8:36
So before joining Inventiva, you you let Bluebird, we've
8:39
mentioned it a couple of times and you let them through a a
8:42
major transformation into a commercial stage company.
8:46
What what lessons are you bringing from that experience
8:49
into to this role and what were the biggest challenges for you
8:53
stepping into that CEO seat? Yeah.
8:56
So that was my first CEO role and I'll, I'll give you a little
8:59
bit of a journey of there, right, because I became CEO and
9:03
two months after I became CEO, we had APDF Nick Leshley, who
9:06
was the founder of of Bluebird and became 270 bio, which had
9:10
its own journey. They had the, the cancer
9:12
products, the car TS and then Bluebird kept the rare disease
9:16
products. And the idea was always that we
9:17
were going to go out and raise some more money right away
9:20
because we knew we had about a year of cash and we needed to
9:23
actually, we need more cash to run.
9:27
Unfortunately, we had a whole put on the subset of our sickle
9:32
cell program, the pediatric subset, which ended up getting
9:35
lifted a year later. But that didn't matter.
9:38
The investors started to flee. So we couldn't raise money.
9:42
And so we had to do what a lot of biotech companies had to do
9:45
through the early twenty 20s, which was to reduce staff, to
9:49
cut costs, to try to extend cash runway.
9:52
And I am super proud of what the team accomplished in the next
9:55
three years because in the next three years the team managed to
9:59
get 3 FDA approvals for three different products, launch those
10:04
products successfully. And actually now I if you look
10:09
at Liftgenia, which is the sickle cell product to compare
10:12
it to the big competitor Cashevi from Vertex that Livgeni is now
10:16
treating more patients than Cashevi is, which is the the
10:20
CRISPR product for for Vertex. But all the way along the way
10:24
there, we did that with less than a year of cash.
10:27
We were always in a cash strapped position and never able
10:31
to fully invest in the company. And that is, that was the my
10:36
biggest lesson is that the markets were down the entire
10:39
time. Gene therapy, while the science
10:42
was widely admired, the business model was uncertain.
10:45
It was very expensive to produce the the therapies.
10:48
There was a doubt that a small company like Bluebird can
10:51
compete against a big company like Vertex.
10:53
And there was a doubt that this would ever become really a
10:56
profitable business eventually, because of the cost of, of, of
11:00
making these therapies. All of those doubts have now
11:02
been dispelled a little bit too late for the original, original
11:05
Bluebird and we, but we were able to transition this company
11:09
to a private equity to Carlisle and and then the company now
11:14
goes on genetics and is doing very well as as far as I as far
11:17
as I know. So the lesson is not going to be
11:19
surprising there. If the cash is kicked, no matter
11:22
how good the science is, no matter how good the team, no
11:26
matter how well you're executing, if you don't have the
11:29
cash and biotech to keep going, then then it, it, it doesn't
11:34
matter. Now, thankfully for the
11:35
patients, for the sickle cell patients that made thalassemia
11:38
patients re lucrative patients, those products are still
11:40
continuing and doing quite well. For our Bluebird investors, it
11:44
was a scientific success, a commercial success, but not a
11:47
financial success. And as I've come to Inventiva,
11:51
I've seen a therapy that I mean, I think this therapy is going to
11:54
be transformative for patients. We get into that in a little
11:58
bit. But one of the first things I
12:00
did when I came to the company was to make sure the company was
12:03
all capitalized. So within my first six weeks, we
12:06
raised $172 million on the US market just to make sure we're
12:11
properly funded through our our data readout beyond.
12:15
And that for me was that actually then allows the company
12:19
to really focus on the science, to really focus on the clinical,
12:23
to focus on the commercial. I should bring this therapy for
12:25
the patients in in a proper way and I will never, I learned that
12:30
lesson in the very, very hard way.
12:31
I will never run a company with a year of cash again.
12:36
What was that like personally, You know, leading a company that
12:39
was always having to be super cash frugal, but also just this
12:43
this element that you you might not make it through that next
12:46
readout next phase and you know, you may have to make layoffs
12:50
etcetera like can't be. Easy.
12:55
I, I was super lucky to be surrounded by a very, very
12:58
dedicated team and the, to go through the number of hard
13:02
decisions that we had to make and to do it with a team that
13:07
could really pull together and, and lock arms and help and, and,
13:12
and make both make the tough decisions and then execute them.
13:16
I think the hardest part all the way along was the fact that
13:20
people were at Bluebird because of the, they believed in the
13:23
mission, they believed in the culture.
13:24
And when we had to part ways with people due to large
13:27
layoffs, that was very, very difficult, right?
13:30
Because they've been part of that journey.
13:31
It was especially difficult the last one we did because we had
13:36
gone through three FDA approvals.
13:38
And I would say the heroes of the company, the, the
13:40
clinicians, the, the, the, the, the, the, the, the clinical
13:44
staff, a lot of our research, we'd let large parts of that
13:48
organization go. And that felt terrible to take
13:51
the heroes of your company and to part ways because the company
13:54
had evolved on to a, to a different stage and we simply
13:58
couldn't afford it. That was the last thing in the
14:00
world we wanted to do. But that was, that was the
14:02
hardest part. And then I think the other thing
14:05
that I learned like that when I went through that is you learn
14:08
we believe entirely what we're doing.
14:10
We believe in the science, we believed in the commercial
14:13
opportunity. We believed in that the patients
14:15
would actually select and the physicians would select with
14:19
Jenny that brought it to the time over cash Chevy and that
14:22
ended up being true. But the investors did and that
14:26
was another lesson I learned is that the, like the investors,
14:29
like the, the, the, IT is very possible to have a wonderful
14:35
product that is misunderstood and is underappreciated.
14:40
And when you're close to it, you can see it.
14:42
And no matter what you say to the investors that's necessary,
14:46
they're it's not, that doesn't necessarily resonate.
14:49
Now, we had other issues going on, like investors didn't want
14:51
to put good money after bad. They could see the short cash
14:54
runway. That was really the issue.
14:55
But that lesson I actually saw as well.
14:59
And then when I came to Inventiva and I started to look
15:01
at this, I was presented with this therapy and the, it's a pan
15:05
P par agonist for mash. We get to it in a second, but
15:09
there was some investor negative sentiment around it.
15:11
Oh, this is a drug that causes weight gain, this drug will
15:13
never work, etcetera. And we looked at the data.
15:16
This is just what that the profile was just excellent.
15:18
And that's why. And when I came to this job, I'm
15:21
like, oh, there's an investor disconnect between the potential
15:23
of the of the, the product and what the investors think.
15:27
I'm very comfortable with that. I've been there before and I
15:29
know that this like the investors are not necessarily
15:31
right. And that's actually proven to be
15:33
true. We're not.
15:35
I'm six months in, seven months in right now and already that's
15:38
corrected. Yeah, I love that.
15:41
I love that. I really want to talk about
15:42
invents even now. So you touched on it a little
15:45
bit there. But ultimately, like what?
15:48
What made you make the move? Why?
15:49
Why did you think it was the this was the next thing for you?
15:52
Yeah. Well, so I left.
15:54
So the new management team came in a Bluebird at the beginning
15:57
of June. So I was planning to take of
16:00
June of 25. I was planning to take a lot of
16:02
time off and to to relax for a little while after very, very
16:08
intense number of years. And the, and I said, I'm only
16:12
going to look at things that are super interesting, right?
16:16
And so I said what you know, and, and my rule was I had the
16:19
headers calling me. And I said, I'm only going to
16:20
look at things that are that I, I know that I can, I can, A,
16:23
that I think are going to be successful and B, that I can
16:25
make a difference to the company.
16:28
And I really was looking at commercial opportunities because
16:30
that's my entire career has been taking phase three assets
16:33
through approval and, and on to the market.
16:39
And I was looking, and I had basically 2 opportunities.
16:42
I was looking at 1:00 and that was it.
16:45
They, they 2 came, they were both very good.
16:47
One was a rare disease company in the Boston area that fit
16:51
right down the middle of my experience.
16:54
And it was getting, you know, in a pivotal trial, getting ready
16:57
to commercialize, nice pipeline, great investors.
17:01
And then they showed me Inventiva.
17:02
And I said, I've never heard of this company.
17:05
And I, when I started looking into it, I said, you know, this
17:09
is a phase three product where we, we read out our data in Q4
17:12
this year. It has wonderful scientific
17:16
pedigree. The the Phase 2B was published
17:18
in the New England Journal of Medicine.
17:21
It has recently been the company's recently been
17:23
recapitalized with by prominent investors NE A/B, VF, Samsara,
17:28
some others as well. It brought in a board share that
17:32
knows what he's doing and Mark Przanski overall and the I'm
17:37
looking at the listen to what investors are saying about it
17:40
and they're still out there saying, well, this drug is good,
17:43
but it's never really going to compete with the other drugs in
17:45
the in the market. It has, you know, that has this
17:48
risk of it has wonderful efficacy, but it's just risk of
17:51
weight gain. This is a world of GLP ones and
17:54
just no one wants weight gain in a GL P1 world, no matter what
17:58
the efficacy is. And it's, and therefore, you
18:01
know, there's some negative sentiment around the product.
18:04
And the more I looked at it and I said, Oh, by the way, it's a
18:05
French company. And I said, well, I know like, I
18:09
know how to come in. I know how to hire a team.
18:11
I know how to raise money to extend the cash runway for this,
18:14
this company. I know how to, I speak French.
18:16
I can run a French team. I've done three times before.
18:19
I, I very much, I, I wasn't scared by that.
18:22
In fact, I was attracted to it because I know the kind of the
18:24
talent base that there exists in France and I can this is
18:29
something that I can actually make a difference for in a
18:32
therapy that I, you know, I love proving people wrong.
18:34
It's like this is a fantastic therapy.
18:37
And if we just if we just tell people about it, right.
18:40
With this, the story, it was crafted in a way that I did not
18:43
think was resonating. We just changed that.
18:46
We just take the same story, tell them in a different way.
18:49
We can be successful. And so that's why I ended up
18:52
coming to Inventiva because I thought this is a therapy that I
18:55
can get to patients, that I can like, that I can help the
18:58
company make a huge difference here.
19:02
Yeah, it's almost like, you know, it just ticked every box
19:06
for. You.
19:10
Are those less familiar with Inmateva?
19:12
Let's just talk about the science, particularly the the
19:15
mash part. Why is it so exciting?
19:17
Yeah. So I'm going to go, I'm going to
19:19
go to the Wayback machine for a second here because I, I always
19:22
find that the, the, you know, people think these drugs kind of
19:25
magically pop from the sky. Someone had a good idea at one
19:27
point. I'll always think that'll work.
19:30
But, you know, the, the drug development process is one of,
19:35
you know, insights all the way along the way.
19:37
The people that have originally made the drug, you know, it's
19:40
taken 12 years to get here, but they had an insight in the very
19:44
beginning that was really, really good.
19:46
This was, it was Fournier was the old French pharmaceutical
19:49
company that owned this therapy. They had launched another PPAR
19:54
agonist. So this this drug is an agonist
19:57
for the for the PPAR receptor and.
20:03
They had or PPAR protein, excuse me.
20:06
And they that was Tricor, which was a was fenofibrate, which was
20:12
a triglyceride lowering drug that had well over a billion in
20:17
sales at the time. And this chem medicinal
20:19
chemistry team said we want to actually make a better PPAR and
20:24
PPAR binds three types of isoforms.
20:26
There's alpha, there's delta, there's gamma.
20:29
And by the time they started designing this, there have been
20:31
multiple pars against alpha against alpha, against gamma.
20:35
And each one of them had a side effect proof that had efficacy
20:38
either in treating triglycerides or diabetes or there's a kind of
20:43
a, a rare liver disease now they're approved for as well.
20:46
But it had side effects and it could be bone density issues.
20:52
It could be in the case of P par gamma, it was fluid retention
20:55
and risk of heart failure. And so this medicinal kind of
20:58
group said, I would say we want to design a pan P bar agonist
21:02
that's going to hit all three different isoforms and have have
21:05
the efficacy of all three while moderating the safety.
21:08
And they did exactly that. They, they had an insight that
21:11
said, hey, we don't want to buy these tightly.
21:13
We want to bind these more loosely.
21:15
We want to bind them equally so that these things are networked
21:18
and we want them to rise or fall and in the same, in the same
21:22
ilk. And then they said that our
21:24
thesis is that'll get, that'll keep the efficacy and get rid of
21:27
the side effects. They did that and they then went
21:29
to animal models and showed that in fact, yes indeed they had
21:34
designed a better mousetrap and the FDA was actually the FDA
21:37
would not allow clinical trials over six months for PRS this
21:40
time without a tox study. They did a two year tox study
21:44
that ended up getting that that limitation lifted not only for
21:49
Lanafibromor, which their the product this became, but also
21:52
for all other heap parts. And then they went into humans
21:55
and they showed, yes, indeed, we have a better toxicity profile.
21:59
And then they went to a phase 2B study for MASH and this this is
22:02
where they chose the indication. So we want to try to treat the
22:05
liver scarring and the liver disease that's associated with
22:09
diabetes, obesity, you know, metabolic disorder, which is
22:13
like now the number one source of cause of liver transplant
22:17
for, for woman and the number 2 for men behind alcohol.
22:21
This disease that's really debilitating.
22:23
That's the indication we chose. And they were able to go into
22:25
this phase 2B and show that yes, indeed, they, they were able to
22:30
address MASH, which used to be called MASH and I'll call MASH,
22:33
which is for the audience is basically liver progressive
22:37
liver diseases result in metabolic dysfunction.
22:41
And then they, and they, and the profile that they developed has
22:45
now gone into the phase three. And that is what we are we're
22:48
bringing forward as well. I won't go into the whole
22:50
competitive dynamic there, but just to say I think this is the
22:53
best drug that is that for for MASH and I think will be a step
22:58
change in terms of patient options as we go forward.
23:02
Yeah, it's awesome. And when you're you're looking
23:04
ahead, what, what are the key milestones coming up for you
23:08
guys? What should people be looking
23:10
out for? So we have our data.
23:12
We have 1000 patients in a phase three clinical trial, another
23:14
400 and an exploratory cohort of of that and we will get our
23:18
phase three data readout in Q4 this year.
23:22
So that is the next, that's the next big step for us.
23:26
So fingers crossed that goes well.
23:29
We'll be looking to show that, you know, looking to show that
23:33
we both have these patients, you know their their liver disease.
23:37
We will treat the liver disease, right, the scarring of the
23:39
liver, and address some of the metabolic dysfunction like the
23:43
dyslipidemia and the diabetes that drives that.
23:46
And those two together kind of help drive a different outcome
23:49
for the patient. Yeah.
23:51
Looking forward to it for sure. And that brings me to my final
23:55
question, which is a question I ask every guest.
24:00
So if you could have dinner with any scientist or innovator, past
24:03
or present, who would it be and why?
24:07
The oh, that's a really good one.
24:09
And actually, no, you actually gave me that question before and
24:12
I actually forgot to think about it.
24:13
So you're going to get me off the cuff here as well.
24:21
I think, you know, I, I'm going to be, I actually think it would
24:25
be, it would be a dinner with Watson and Crick, right?
24:28
I, I do, I mean, the fact that they did that paper mache model
24:31
to figure out the, the double Helix and just I would want to,
24:35
I would want to hear about that Eureka moment that they had
24:39
overall, I think would be my, would be mine and then has a
24:44
genetics major in college, right?
24:46
That's what I was learning. I used to say that like we
24:47
learned genetics in the dark ages.
24:49
So I learned it. I was in College in 1992 to
24:51
1996. So they were the kind of the
24:54
foundation of what we were, We were learning and then to look
24:58
and I would want to ask them now, what do they think about
25:00
everything that's happened now? Because everything I learned in
25:02
college, it was obsolete. I had to go back and take some
25:06
courses from Berkeley a couple years later because all the
25:08
genetics and the immunology I learned was obsolete.
25:10
And I would love to ask them what they think about RNAI
25:14
interference now. And would you ever guess that,
25:16
you know, that there could be the fact that these, this, this
25:19
simple inheritance mechanisms could be so complicated?
25:22
So I'd love to have that discussion with them, yeah.
25:24
That's such a good answer. Very.
25:27
Yeah, Impressive off the cuff that.
25:32
But look, it was an absolute pleasure to have you on Andrew.
25:34
You know, really exciting what you guys are doing.
25:36
Looking forward to see it come through and please everyone
25:41
looks like and subscribe to the Bio hub.
25:43
And thank you so much again, Andrew.
25:45
Thank you.