Latest / The BioHub - by Avetix / Episode 207 - Ola Wlodek - CEO of Constructive Bio

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Episode 207 - Ola Wlodek - CEO of Constructive Bio · The BioHub - by Avetix

0:06
So welcome back to another episode of the Bio Hub, the
0:09
Avetics podcast. Today we're delighted to welcome
0:11
on Ola Vladek, who's the CEO of Constructive Bio and leading one
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of the most exciting companies in synthetic biology.
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Ola began her career as a scientist, earning a PhD from
0:22
the University of Cambridge before building a track record
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of leadership across some of the some of the UK's most innovative
0:28
biotech companies. The CEO of Constructive Bio, Ola
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is leading the commercialization of pioneering technologies that
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enable scientists to rewrite the genetic code of living
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organisms. In today's discussion, we'll
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discuss the synthetic biology space, constructive BIOS
0:45
pipeline, and the next milestones for the company.
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So Ola, it's an absolute pleasure to have you on.
0:51
How are you? I'm very good.
0:52
Thank you, Tom. And I'm very excited to be
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talking to you today about Constructive.
0:57
Yeah, look, it's a, it's an absolute pleasure to have you
0:59
on. So let, let's just dive into a
1:01
little bit about your journey through the field, how you got
1:03
to where you are today. So you've had a, a fascinating
1:06
journey from academia into company building.
1:10
Can you just take us back to your time as a scientist and
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walk us through the experiences that gradually pulled you
1:16
towards becoming ACEO rather than staying purely in in
1:19
research and staying in the lab? Absolutely, and I will start
1:24
from stating something that is obvious to me, but perhaps not
1:28
to everyone who moves from bench to to the boardroom.
1:32
I didn't leave science because I loved it less, right?
1:36
I really love science. I actually like bench work and I
1:41
left the bench because I started being captivated by different
1:45
bottlenecks, right? It's all good to do quality
1:49
experiments with your own hands. And I still think it's very
1:52
beautiful and it's very interesting to design a good
1:55
experiment, deliver goods, data set, and then analyse it and
1:58
learn something that nobody has ever learn before you, right?
2:03
I think this is the core, core enjoyment of, of being a
2:08
scientist. But at some point, I've realized
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that I could be a better enabler of what is being done than a
2:16
person delivering all the data. And what I still do, I really
2:23
value the individual contributors because they are
2:26
the engine of our industry. And no matter how good is the
2:29
vision, no matter how good is the strategy, you have to
2:33
deliver a really good data in the end of the day.
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And that happens through the hands of a scientist.
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But I kind of mutated from being fascinated about the question,
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is this true to the question, why isn't this ready and why
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isn't this yet delivered? And that second question moved
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me from the hands on science to more and more leadership roles.
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And the thing that pulled me was never a title or kind of
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particulars strategy of progress in career or obsession of, you
3:09
know, becoming a manager and then the CEO.
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I just wanted to get things done and get things delivered.
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So that is what has been driving me from from bench, as I've
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said, to more challenging managerial roles, Although I
3:26
really sometimes really miss science.
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I think perhaps once a month. I think like if only I were in
3:31
the lab, that would be so good and so simple and so fast and,
3:35
and you know, like I love working with science.
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I would never change it to any other career.
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So. So I'm still a scientist at
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heart. Yeah.
3:43
Was that quite an easy step, taking your sort of science hat
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on off and away and becoming becoming ACEO and having to
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think about other functions of the business and not just the
3:52
science? Was that was that difficult for
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you to do? It is difficult.
3:56
I still think a lot about science and I explained this to
3:59
myself with that very strong belief that the science is the
4:02
most important thing that we're doing as a company.
4:05
We're building company. This is science first.
4:08
The science is the engine of what we're doing.
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So it has to work in the right way, right.
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So I have a drawn view of what's going on, what's going on with
4:19
science. But I'm also very lucky.
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I'm working with some incredibly talented people like our VP of
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R&D, Daniel de la Torre, and of course our founder and CSO,
4:28
Jason Chin, who a far better scientist than I've ever been.
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So I'm still having eyes on the science, making sure everything
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goes well, but I am supported and surrounded by people who
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make it much easier for me to have enough time to work on
4:45
strategy, on the business model, on venture capital journey and
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so on. OK, amazing.
4:52
And for for people who might, who might not have a science
4:55
background, how would you explain what constructive bio
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does in a way that captures both the technical depth and also the
5:02
real world impact of the company and what what you're doing?
5:05
Yeah, so every living thing on earth.
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So you, a tree or a virus is built from the same repertoire
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of 20 amino acids. These are building blocks of
5:20
proteins, and that's the entire palettes that nature has ever
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had. So we rewrite the genetic code
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of a cell so it can build proteins and peptides with
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entirely new blocks that biology has been never able to use in
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the past. So we're not really a drug
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company or a chemistry company per SE.
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We are the cell reprogramming company that writes new genetic
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codes and that allows us to manufacture new nature molecules
5:53
outside of the nature's repertoire.
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And the real world impact is pretty simple.
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We make medicines that are made from new to nature building
6:03
blocks, so they haven't existed before.
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Not because nobody was clever enough to think that they will
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be a good idea, but because seller toolkits literally
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couldn't make them before. So we expand that toolkit.
6:18
Right, OK. And you guys are a platform
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company as well, right. So how should we think about the
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relationship between the underlying technology platform
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and the products or applications that that sit on top of it?
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Yeah. Just talk us through that as
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well. So I am a massive platform
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aficionado, I'm massive platform advocate.
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And no matter what others say about platform these days, I
6:40
will always stand up for platforms.
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And if you think about like technical terms, you can think
6:46
about the platform as a foundry that produces chips, right?
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So chips would be the product and the platform is that foundry
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that can make any cool product that that you, you imagine.
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And from that perspective in in that constructive, the platform
7:03
is the recorded Organism with new rewired genetic code and
7:08
that is that durable factory that keeps pumping out new
7:15
molecules with new to nature building blocks.
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So product will always sit on top of that machine, that
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foundry that that is our technology.
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And I think sometimes people especially recently when the
7:29
venture capital access was limited started to thinking
7:32
about platform versus product as some sort of a trade off, right.
7:38
And it should not be a trade off.
7:40
It should be a flywheel that keeps pumping out new exciting
7:43
products, right. You can only do that when you
7:46
have enough capital to to maintain that model.
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But a real platform is something that will generate value over
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and over again. And, and perhaps part of the
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problem we have with the platform versus product
8:00
discussion is that sometimes people try to call platform
8:04
things that were not platforms. So a set of similar antibodies
8:07
is not only a platform is a set of antibodies or a ability to
8:14
discover new targets. I would argue that that's not
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exactly a platform. This is a some sort of discovery
8:20
engine, right? That's you still don't have the
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ability to make the new product straight.
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So at Constructive we are building the company around this
8:29
strong platform thesis that's creating repeatedly value over
8:33
time will compound. And This is why I know that we
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have a technology that enables something that nobody was able
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to do before and we have a technology that can on the
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repeat produce outputs of that technology.
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So peptides and proteins with new to nature features.
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So I bet big on the platform and I think, you know, we will bring
8:58
many cool things in the future to the markets.
9:02
Yeah. So as you look into your
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pipeline today, I, I guess, could you just give us a high
9:07
level overview of, of how that looks, but which areas or which
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areas are you personally most excited about and what makes
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them particularly like compelling or differentiated in,
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in what I guess is quite a, a competitive space as well, let's
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say? Yes.
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So we don't have yet everything in the public domain.
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So I will be speaking a little bit in a cryptic way, but you
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know, with the confidence of of what we're working on.
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We have some very exciting thing going on in liver disease, which
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is enabled by new to nature features.
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And I think that it's based on the really cool science.
9:47
The data has been compounding over time showing us that we are
9:51
on the right track and we are polishing it towards the really
9:54
cool new molecule. So I hope in a few months we'll
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start having a good conversations with people
10:00
outside of constructive about what exactly we're working on.
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I'm excited about that because it's a very big unmet need.
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There are problems with liver disease which are related to the
10:12
liver fibrosis that have not been resolved even with the
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advent of the really exciting GLP one compounds that are
10:20
making patients lose considerable amount of weight
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and also improve their liver health.
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So I think there is something that we are doing in a very
10:27
unique manner that is enabled by non canonical amino acids.
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So I'm very excited about that. Additionally, I'm very excited
10:35
about some of our work in oral peptide space.
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I think that again, we're coming from a very unique angle and the
10:43
use of non canonical amino acids that will bring the features
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that cannot be reached through traditional protein and peptide
10:49
engineering. Yeah, that's exciting.
10:52
And so the synthetic biology space, it's obviously an area
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you know quite well. It's also an area that's
10:59
becoming increasingly crowded and and a competitive space as
11:03
well. When you just take take a step
11:05
back, what would you say truly sets Constructive Bio apart from
11:09
maybe other companies that are working in this field?
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Yeah, again, I think it's very easy when you read all the
11:16
articles about synthetic biology or, or, you know, you follow X
11:20
or social media or even LinkedIn, people very often talk
11:24
about synthetic biology as a business model.
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And it's definitely not a business model.
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Or they talk about it as some sort of magic tool that will
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sort all the biology problems, which again, I think, I think
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it's largely overstated, right. But where we are very unique in
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that space is that we are able to engineer entire genomes.
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We are able not to engineer a gene or a circuit of genes, but
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harmonize everything that is in that genomic sequence.
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We are able to introduce objective functions which are
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industry relevant to the genome design and as a result we can
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create a new organisms. So that is a step change and
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that is what differentiates us over other synthetic biology
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companies. I think that we are based on
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truly enabling technologies, so not the iterative improvements
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of, as I've said, manipulating genetic circuits or or
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individual genes. So I I think the technology
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stack as well as the tailwinds coming from the market, the
12:30
interest in GLP 1 space is really turning constructive into
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something that has a tangible value proposition and not just a
12:40
cool technology stuck behind it. So I would say differentiation
12:44
for constructive is based on the entire genome writing capability
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and the really cool markets that we have access to.
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Yeah. And as you look across the wider
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field, who are the companies and I, I never like to use the word
12:56
competitors because I think ultimately what you're doing is
12:59
for the patients, right. But who are those companies that
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you're sort of up, I guess up against in, in the market there?
13:06
There is across, I guess, not just not just Europe, but in the
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US as well. Yeah, yeah, absolutely.
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So, you know, if you talk synthetic biology, Ginkgo
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Bioworks will immediately come to your mind and they have
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really amazing robotic lab set up that gives us a lot of scale
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to use, which is pretty impressive.
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They are not exactly competitor because it's a service based
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business that's, you know, serves number of partners, but
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doesn't bring to a table A new underlying technology or IP
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stack. They their advantage is scale
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based, I think. I think there's a lot of good
13:49
things to be said about Ginkgo and people, people are obviously
13:55
sometimes disappointed with their, you know, market cap
13:59
trajectory, but it's a company that does synthetic biology at
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really big scale. If you think about other
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competitors, you will have to look at the product level
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competitors, right. So if we talked about the liver
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disease, the competing companies are going to be competing on the
14:15
liver centric assets, right. So this gives us actually I
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would say an advantage because even if we lose on the
14:22
particular product, we still can compete with other products that
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will be coming out from that platform background.
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That's that we've discussed earlier.
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So, you know, there's a plenty of cool companies in the world
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that work on on synthetic biology, new age molecular
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biology, trying to give a lot of change to the proteins.
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And I think where we have to compete in a very ambitious
14:50
manner is the protein engineering.
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With the advent of artificial intelligence for protein design,
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everyone now can design very new and cool proteins.
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I like the fact that they are still restrained within the
15:06
pallets of the canonical amino acids.
15:08
Like you can design lots of variants.
15:10
The chemical space is quite big, but you cannot teach the natural
15:15
protein to do chemical reactions that canonical amino acids are
15:20
not able to do chemically, right.
15:22
So that restricts the competitors in a space where,
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yes, there is also variance. Let's there is more screening,
15:29
there is more testing, but they actually limited by chemistry.
15:32
So, you know, I, I watch the space very carefully.
15:35
I'm very excited about progress in incident biology.
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In the end of the day, the progress for the patients is
15:41
progress for the patients. The competition is a good thing
15:44
and then the bio economy is, is so big that's I think everyone
15:48
will will be allowed to have a good slice of pie.
15:51
I think the competing for the venture capital is is more
15:54
challenging than than when you deliver something how how the
15:58
market is going to look like and the future will look like.
16:01
Yeah, for sure. And so as you look ahead over
16:04
the next few months, over the next couple of years, what would
16:07
you say are the key milestones or inflection points that will
16:10
define progress for constructive bio, you know, whether that's on
16:13
a on a clinical side or fundraising partnership, just
16:17
just talk us through. Yeah.
16:19
The most important thing that we are currently really focused on
16:23
is partnerships. We have some things in the works
16:27
that we are building towards announcing at some point and
16:33
when when we get there, I think we're going to be very happy as
16:35
a company and I'm very optimistic about the trajectory.
16:38
Second thing is we're writing A next generation strain, which
16:43
has got a really cool genome design.
16:46
We almost at the at the ends of that journey and the team has
16:51
been working so hard. They have so amazing results.
16:54
I'm I can't wait to tell the world how this genome pans out.
16:58
I think it's going to be pretty exciting and I think the strain
17:01
should be a really robust industrial strain.
17:03
So the team is excited, I'm excited and hopefully the
17:06
partners will be excited about what the strain delivers.
17:09
And finally, we're working on some really cool new chemistries
17:13
that we will be able to introduce to proteins and
17:16
peptides that is progressing for quite some time.
17:19
And I think we again are arriving at the advent of a
17:22
really cool technical milestones.
17:25
So this is what excites me about constructive right is a
17:27
combination of a commercial milestones which we very close
17:31
and a really big technical milestones that we are building.
17:36
And I can't wait to go out to the world and talk about this to
17:40
to partners, to users in academia as well on how this
17:44
technology enables really amazing things.
17:49
So we don't have any clinical constructive based milestones
17:55
ahead of us, but at some points it is possible that our partner
18:00
is going to be going very fast to the market with their
18:03
molecule that we'll be making with our technology and I can't
18:06
wait for that. Yeah, for sure.
18:10
So constructive bio, you guys are based out of Cambridge,
18:15
obviously one of the, you know, one of the the the hubs for, for
18:18
biotech across the world. How has been based in the UK
18:22
shaped the way that you've built the company both positively and
18:26
negatively? And what would you see as the
18:28
biggest strengths of the UK ecosystem and when it comes to
18:31
deep tech and and biotech innovation?
18:34
So, you know, our science came out from the Cambridge
18:37
ecosystem. OK.
18:39
So if you think about this, I I think you can almost start
18:43
thinking about the unfair advantage that Cambridge has
18:47
where it attracted phenomenal researchers.
18:50
And Jason Chien, our founder was based in Cambridge when where he
18:54
delivered some of his most game changing discoveries and
18:58
technologies. The writing of the first world
19:01
entirely recorded synthetic genome showing that those
19:05
strains can incorporate multiple new to nature chemistries,
19:09
showing genetic code expansion on steroids in his lab.
19:13
All this was incredibly exciting, right, and happened in
19:16
Cambridge. Our board director Greg Winter
19:19
is a Nobel Prize winner in phage display for antibody engineering
19:24
in 2018, right? He's also a Cambridge
19:27
institution and having synergies between such brains happened in
19:33
Cambridge right. And if we think about this as a
19:37
as A and for advantage is a very dense ecosystem of really
19:42
amazing science. So as a result, we actually have
19:45
access to a very good talent. I slightly laugh about it as the
19:52
Eastern European, but the cost structure of running AUK company
19:56
has became much more palatable over the last 20 years than than
20:00
when I first moved to the UK. So so.
20:04
Venture capital takes you a long way in the UK and I think that
20:08
also attracted some of our investors, not just because
20:12
we're cheap, but because of the talent and good cost structure
20:15
synergy. People are slightly understated.
20:21
So they do very high quality work, right?
20:24
And they, they don't oversell and they don't, you know, fake
20:32
it till you make it in the UK. So, so it's, it's easy to run a
20:36
science first company because everyone is quite serious about
20:39
that science. If I were to say what is
20:43
challenging about the UK company is we, we, we do have a
20:49
challenging employment law here, which makes it difficult to
20:52
pivot or move fast as a as a company.
20:55
There is much more venture capital in the US than it is in
20:59
the UK ecosystem, although those things are a little bit more
21:02
fluid than than perhaps were a few years back.
21:06
And I would like people in UK to have the same ambition as people
21:13
in the US half right. So there there's lots of really
21:17
good companies, there's lots of really good inventions.
21:20
And we are still talking about, you know, selling to pharma in
21:24
three years and, and, and that being, you know, a final boss of
21:29
growth as a start up. Well, I would like to build
21:33
something generational. I would like to build something
21:36
super ambitious. I would like to build a company
21:38
which is recognized for its science, for its commercial
21:43
trajectory, but is not there to disappear in few years, right.
21:47
So, and when I say this to US investors, very often they
21:52
listen to me, they're interested and, you know, they are
21:56
supportive. And sometimes in the UK people
22:00
would say, oh, be more realistic.
22:02
Obviously you have to sell. Obviously you have to move to
22:05
the US. Obviously you shouldn't grow
22:06
fast. And I, I don't think it's that
22:09
obvious as, as people would like to say, so, you know, building
22:15
requires capital. And I think unless this is
22:17
unlocked, we're going to be in the same place.
22:20
But UK is a good place to, to have access to talents, to have
22:24
a good synergy between scientists and the business.
22:27
And, and these days everything happens online.
22:31
So it doesn't really matter whether we're based in
22:34
Whittlesford or whether we're based in, in, in Boston.
22:39
So I think it we can also turn into our advantage.
22:42
Yeah, that that takes me really nicely.
22:44
On to on to my next question actually.
22:47
Yeah, well, like you you just mentioned then about, you know,
22:49
you want to maybe continue independently versus being
22:52
acquired potentially. Just talk us through that.
22:56
You you know, you see a lot of early stage biotech as soon as
22:59
there's the opportunity to sell, they'll they'll maybe take that
23:02
option up and they'll look to be acquired.
23:05
What just talk us through your ambition on, you know, building
23:07
the company versus being acquired like?
23:10
Yeah. And I want to start from kind of
23:12
a Gen. generalist. Thoughts.
23:16
Your exit strategy should be aligned to your business model
23:22
and your capabilities, right? And by capabilities, I don't
23:25
only mean science, but I mean science, capital availability,
23:28
team strength and so on, right? So it's not wrong to develop an
23:34
asset, place it on in the hands of big pharma and get to the
23:38
patients this way, right? Like it would be irrational for
23:41
us to expect every start up to go for commercial routes with
23:45
with every product, right? But at the same time, if
23:49
everything goes well, Constructive is the company that
23:54
will expand with biological manufacture.
23:57
And I believe the world will be in the place when the new
24:02
molecule with new nature features will be needed.
24:05
People will go to Constructive, right?
24:08
And that will required us to build the company for the long
24:15
game. So I want to be very patience
24:20
and lean with how we deploy the capital as a company, but
24:24
carrying on building the capabilities, building the
24:27
capacity, building the commercial muscle and building
24:30
the company for as I've said for the for the long term, we are
24:35
venture capital founded and as a result, I can't predict what the
24:42
future will exactly bring. But my plan A is to build
24:45
something really strong and big and as I've said, generational.
24:51
Yeah, for sure. I, I love that mindset for sure.
24:54
You, I've not heard that that much that much before.
24:57
So I love that you think in long term about this as well.
25:01
I think another thing, obviously platform companies often face
25:04
the challenge of balancing breadth with focus.
25:07
How do you personally think about that trade off when you're
25:10
trying to build constructive bio as well?
25:13
Yeah. So our platform is permissive
25:17
for doing the same set of activities that deliver
25:21
different outcomes. So our platform provides enough
25:27
breadth in terms of like outcomes with a limited amount
25:32
of build up. And I think this is this is
25:36
again our unique strength and unfair advantage of our
25:39
technology that with one strain with rewired genetic codes, we
25:43
can incorporate, you know, now 10's and in the future hundreds
25:48
of thousands of different chemistries into different
25:51
proteins and peptides. And that is because we have this
25:54
plug and play system where we have a chassis with space in
25:58
genetic code and we plug in the machinery for new nature
26:03
building blocks into that chassis in the 1st place.
26:06
And as a result, like we don't want to do too much in terms of
26:14
the product space. I want to work in collaboration
26:18
with product specialists when we create the chassis handed to the
26:22
hands and then they characterize the products in terms of
26:26
clinical characterization and so on.
26:28
So in terms of depth versus breadth of a platform, I think
26:35
we need to be very deliberate about what breadth is needed.
26:40
Focus on things that genuinely add value, focus on things that
26:44
are different from what non canonical amino acids, the
26:47
natural ones can do. And for for all the science
26:51
nerds that that listen, the good example will be properties like
26:54
hydrophobicity, right? It's not a unique property to
26:58
non canonical amino acids. You can have natural amino acids
27:00
which are relatively hydrophobic.
27:03
Therefore, As for now, we not focus, we don't focus on such
27:08
new chemistries which are new to nature, but they are not game
27:11
changers at the moment. We're focusing on very exotic
27:15
and useful chemistries that we bring to proteins and peptides.
27:19
So we are optimizing the range of things our platform will be
27:25
implementing and we are focusing on the high quality of that
27:30
platform, right. So we for the last few years
27:35
since our inception as a company, we're really focusing
27:38
on the industrialisation of the strain that we're using.
27:41
So we can go to any facility in the world and give them our
27:45
strain and it will be producing at multi gram per litre as as we
27:50
are doing at the moment of the proteins or peptides with
27:52
multiple non canonical amino acids.
27:56
This means that we are doing things that matter from the
28:01
platform perspective, but we are not doing anything and
28:04
everything that the platform in theory could be able to to
28:08
touch. So it is a challenging trade
28:10
off, but we are intellectually addressing this question on the
28:16
basis of intentionality, on the basis of what the market is
28:21
telling us and what the partners are telling us about what
28:24
exactly they need and what matters to them.
28:26
I think biggest mistake of the, the first wave of synthetic
28:31
biology companies was to operate on assumptions which were not
28:37
tested in the real world's context.
28:41
And people sometimes develop things which were beautiful, but
28:44
were not usable outside of the laboratory.
28:46
And, and we have learned from those lessons and we are making
28:51
things which are industry relevant, which are welcomed by
28:55
the, the, the industry. And, and I think, I think that's
28:59
our secrets to, to strength as a, as a technology developer.
29:05
Yeah, amazing. I I can tell how how passionate
29:08
you are about platform companies.
29:10
So that's great. And, and this is a question that
29:12
we always finish with on the podcast as well.
29:16
If you were to sit down and have dinner with any free people from
29:18
past or present, who would you, who would it be?
29:21
Why? It can be people from from
29:23
science, from sport, from business, from history.
29:27
Yeah. Who would you choose and why And
29:28
and what would you want to learn from them or explore in that
29:32
conversation? Yeah, yeah.
29:33
Not the easiest of questions to answer, but.
29:35
No, it's, it's a, it's a very, very difficult question.
29:39
And and I'm going to say, I think I would love a dinner with
29:44
Jensen Huang, OK, Because I think what he built at NVIDIA is
29:48
super interesting. And the fact that he built it
29:51
with so much longevity as a, as a leader and with such a tech
29:54
focus is pretty fascinating. I think I would love a dinner
29:59
with some, some very amazing brain scientific brain to learn
30:05
a little bit more about decision making and the intellectual path
30:09
to delivery. So, so perhaps someone with a
30:15
amazing trajectory of of delivery think about like female
30:21
scientists that I would like to dine with, maybe, maybe a
30:29
Marekiris Kodovska as a Nobel Prize winner or yeah, I don't
30:35
know. And I also quite like artists,
30:38
but no one comes to my mind right now.
30:40
So people who think in a very orthogonal way to to scientists
30:44
and business people. So if I had the one business
30:47
leader, one very clever scientist and one someone who
30:50
thinks and sees worlds in a very different way, that that could
30:53
make a very good tree of dinners.
30:56
Yeah, amazing. Well, look, thanks so much for
30:59
taking the time and helping us out with this.
31:01
It sounds super exciting what you're building at Constructive
31:04
bio. I'm looking forward to seeing
31:05
the next inflection points that you guys and yeah, keeping an
31:09
eye on on some of the announcements, but I'm sure will
31:11
come out so. Absolutely.
31:13
I will. I will thank you so much and I
31:15
will definitely keep you posted about the next next big things.