Latest / The BioHub - by Avetix / Episode 243 - Johanna Kaufman: CSO at DeckBio

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Episode 243 - Johanna Kaufman: CSO at DeckBio · The BioHub - by Avetix

0:06
So welcome back to another episode of the Bio Hub the of
0:09
Essex podcast. Today, we're thrilled to be
0:11
joined by Joanna Kaufman, who's the CSO of Debt Bio.
0:15
Joanna has spent her career at the forefront of cancer
0:17
immunology and drug development with leadership roles spanning
0:20
biotech startups and global pharma companies including
0:23
Codogenics, GSK, Tesaro and Genosha Biosciences.
0:28
In today's discussion, we'll talk through the T cell engager
0:31
space, an insight into deck BIOS pipeline and the next major
0:36
inflection points of the deck bio.
0:38
So Joanna, thanks so much for coming on.
0:40
How are you? I'm doing well, thank you for
0:43
having me. Yeah, look, it's a, it's an
0:45
absolute pleasure to have you on.
0:47
So let's just start off with a little bit about your journey
0:50
through the field. So you've built your career
0:51
across academia, large pharma companies and now Chief
0:56
Scientific officer of an early stage biotech.
0:59
Can you just talk us through your journey through the,
1:02
through the field and how ultimately you ended up ended up
1:05
where you are? Sure.
1:06
Happy to do so. So I started out sort of in a
1:10
traditional academic setting, obtaining my PhD at German
1:14
Cancer Research Centre, which is essentially the German version
1:16
of the NCI. And then I moved to the Boston
1:20
area for my postdoc at Birmingham Brigham and Women's
1:22
Hospital. And obviously those are my
1:26
scientific foundations in the oncology space.
1:31
While both of these organizations are affiliated
1:34
with hospitals in a in a strong sense and have translational
1:39
aspirations, I personally didn't feel sort of, I couldn't see the
1:46
impact of the research that I was doing on patients, which is
1:50
ultimately the reason why I ended up in the biomedical field
1:53
to begin with. So I felt like industry might be
1:57
the better sort of column of the ecosystem, where I could see
2:02
that translation of science to drugs and patients in a more
2:07
direct manner. And that's how I decided to move
2:10
into industry. I had the opportunity to make
2:14
that jump by joining Genosha Biosciences where I initially
2:19
worked on vaccine development for infectious diseases and
2:22
later on for cancer. I eventually decided to learn a
2:27
different business model by going to a company called
2:30
Tesaro. They are an interesting company
2:34
in the sense that they are somewhat built backwards.
2:37
Their business model was to in license established drugs and
2:43
then bringing them to the correct patient population.
2:46
And with each licensing round the drugs went earlier and
2:49
earlier stage in their development.
2:52
So the research function was actually built out last at
2:55
Tesaro and separately they operationalized their science
2:59
exclusively externally through collaborations and contract
3:03
research organizations, which at the time pre COVID was quite a
3:07
novel way of operationalizing science.
3:10
So that was a a fantastic learning opportunity and got me
3:14
back into my core area of immuno oncology.
3:17
TESARO was then acquired by GSK and I stayed on through that
3:21
transition and helped integrate the immuno oncology portfolio
3:25
from TESARO into GSK and started building a lab based team in the
3:31
Boston area for GSK Oncology. I learned a lot during my time
3:38
at GSK and the leadership and scientific skills I learned from
3:44
examples and others in the organization are still the
3:48
foundation to everything I do today.
3:50
However, ultimately I needed to realize that the way of working
3:56
in pharma and the processes you need to put into place to make
4:00
100,000 people go in the same direction are not aligned with
4:04
the nimble innovative biotech approach that I personally
4:08
prefer. And that is why I followed the
4:10
call to go to Codogenics into a small biotech with 20 people at
4:14
the time building out an immuno ecology department there and had
4:19
a quite broad remit and scope. And that helped me build sort of
4:24
the experience to now join Deck Bio as Chief Scientific Officer.
4:28
And my role also in a start up company obviously is is quite
4:32
broad. OK, amazing.
4:35
You you've had the opportunity to work on a range of different
4:38
therapeutic areas throughout your career.
4:42
What? What was it about Deck Bio that
4:43
convinced you that this was the company that you wanted to to
4:46
help come in and build at this stage of your career?
4:50
Yeah. I mean realistically speaking,
4:53
at the time I joined Deck Bio, Immuno Oncology as a sub
4:57
specialty within the oncology field had gone through difficult
5:02
times in the sense that the immense promise that the initial
5:07
sort of impact of PD1 PDL 1 axis inhibitors has provided for the
5:12
field. It was difficult to follow on
5:15
with other equally commercially successful medicines.
5:19
So immuno oncology was a difficult area.
5:22
But within that space, T cell engagers, which is the focus
5:25
modality for Deck Bio has actually been quite popular.
5:29
So I felt strategically that was a good modality to support what
5:34
really impressed me beyond the scientific approach that I'm
5:37
sure we can dive into further as we move through this
5:41
conversation. What I really felt was a strong
5:45
suit for the company was that they thought about
5:49
manufacturability of drugs and therefore sort of ultimately
5:54
patient access very early on even as a premise and the
5:59
foundation of the company. And that is an area that is
6:02
often neglected by those who just found a company based on
6:06
innovative scientific ideas. And I felt it was that
6:10
combination of innovative science together with the longer
6:15
term deliverable of medicines thought process UMM that really
6:20
convinced me that Deck Bio is a good company to join and help
6:24
build. Amazing and it's a deck bio is,
6:27
uh, has, has focused within T cell engages, which has been a
6:31
really exciting area across oncology over the last decade.
6:34
We've had the we've had the pleasure of hosting a few people
6:36
on the podcast that have been in this space.
6:38
Uh, and I've worked with a few companies in this space.
6:40
So super exciting. Umm, particularly within
6:44
hematological cancers, I think what's been proven is that it's
6:47
been difficult to translate this over into solid tumours or
6:51
there's not been maybe as much success as maybe people would
6:54
have first expected. Just from your perspective, what
6:57
are the biggest biological and clinical barriers that have held
7:00
this field back and why have these challenges been quite
7:04
difficult to treat? I would say there are three main
7:08
scientific reasons why the success of T cell engagers and
7:13
solid tumors has been restricted to niche indications and it
7:16
hasn't had the same impact as in hematological malignancies.
7:21
The first one is the tumor microenvironment that you find
7:25
in solid tumors, which is suppressive.
7:28
It's actually also a physical barrier to drugs entering and
7:33
reaching all tumor cells. And if we're looking at the
7:36
field as a whole, I think we're we're thinking through
7:40
strategies to make sure that the T cells that you do engage with
7:44
the T cell engager are as active as they can be.
7:47
Specifically I'm thinking about Co stimulatory domains that are
7:51
being added such that you end up with sort of Tri specific
7:55
molecules. And there are also improvements
7:58
on affinity maturation to ensure you do engage the target that
8:02
you see very effectively. This is a double edged sword
8:07
because you can over stimulate T cells and then drive them into
8:11
dysfunction or exhaustion, which is actually what you don't want
8:14
to achieve. So you can maximize the the
8:17
effect of the tumor infiltrating T cells that you do get.
8:21
So I think as a field we have a few more technical pieces here
8:26
to to solve. The second reason why it is
8:31
difficult to leverage T cell engagers in solid tumors is the
8:36
scarcity of suitable cell surface targets.
8:41
They're very clear and well established cell surface targets
8:45
in the heme space BCMAC D20 CD 19.
8:49
But when it comes to solid tumors, there are very few that
8:53
actually have a specific enough expression pattern that is it's
8:58
tumor exclusive, but does not occur in healthy cells that that
9:04
you can target. And so for a potent modality
9:09
like T cell engagers, they're actually quite a few safety
9:13
liabilities if you choose a target that might be strongly
9:16
overexpressed in cancer, but also has residual expression on
9:20
healthy cells. So we have to find creative ways
9:23
to to address that. And then the last piece I think
9:26
that we need to think about is heterogeneity, which is a lot
9:31
larger in solid tumors as it is in hemalignancies where
9:37
different cell types within the same tumor nodule or within the
9:41
same patient might express targets in a very different
9:46
manner. And that is another area that
9:49
that the field needs to address. People are doing this through
9:54
sort of creating, getting complex molecules that target
9:57
multiple targets at the same time, which then can create
10:01
molecules that might be quite difficult to manufacture.
10:05
So these are I think to me the key three areas that the T cell
10:09
and Gator space needs to work on and Deck Bio has solution to a
10:14
couple of these. Nice.
10:16
That sounds exciting for for people that might not be as
10:19
familiar with Deck bio. I know you guys are sort of
10:22
emerging and and now growing, but can you just paint a picture
10:26
of the company? You know, what is the core
10:27
scientific hypothesis that the business was founded upon?
10:31
What met need are you trying to address for patients and what
10:35
would success ultimately look like for the company if if you
10:38
deliver on on the vision that you set out?
10:41
Yeah. At Deck Bio, we are addressing
10:44
the last two of the hurdles that I just mentioned.
10:47
So the first one was the selection of appropriate targets
10:52
to really find cancer cells specifically ideally with
10:56
targets that are not expressed elsewhere in the human body.
11:00
And we are addressing this issue by choosing a different target
11:05
class, namely peptide MHC complexes.
11:08
So the majority of the proteins that have a tumor exclusive
11:13
expression pattern are actually expressed intracellularly and
11:17
are not naturally available to a biologic like AT cell engager on
11:22
the cell surface. However, every intracellular
11:25
protein gets sampled as part of natural immune surveillance
11:29
mechanisms of the body and pieces peptides of these targets
11:34
are displayed in the context of HLA molecules or MHC molecules
11:39
on the cell surface. And this makes intracellular
11:44
proteins accessible to a biologic like AT Cell Engager
11:48
and this allows us to choose very tumor exclusive targets.
11:52
The second issue that we then have is tumor heterogeneity as
11:57
well as copy number concerns because peptide MHC complexes on
12:01
the cell surface are comparatively rare and low
12:05
abundant in comparison to something like ACD 20 as a
12:10
popular target in the heme space.
12:12
So we are addressing that and that is the main premise behind
12:16
Deck Bio's approach through multi peptide MHC targeting.
12:21
So we are selecting signature of multiple target proteins that
12:25
are expressed exclusively in cancer that get processed into
12:28
peptides that are either identical or highly similar to
12:32
each other such that they get loaded into the same HLA complex
12:37
and present a structure on the cell surface that can be
12:40
recognized by a single binder. This means we create a very
12:45
simple bispecific T cell engager that is easy to manufacture, but
12:50
it recognizes multiple targets and that means that copy numbers
12:54
are higher because expression is higher, more patients are
12:57
expected to respond to therapy, and because there is
13:02
combinatorial optionality of which target protein can derive
13:06
the peptide MHC complexes on the cell's surface, you can address
13:10
inter and intratumoral heterogeneity and all of this
13:14
with a simple to manufacture molecule.
13:19
This then obviously means that we can address larger patient
13:23
population and that addresses also some of the market and
13:26
commercial concerns people have about peptide MHC targeted T
13:31
cell engagers. Success ultimately will look
13:34
like for us to generate durable responses because resistance
13:40
mechanisms are harder to occur when you have to lose multiple
13:43
target proteins as opposed to just one.
13:46
So durable and deep responses are ultimately what we're going
13:52
after in major solid tumor indications.
13:55
Nice. That sounds super exciting.
13:58
Just to delve into the pipeline a little bit further, in
14:01
particular the LEAP programme, I guess like every biotech will
14:05
have difficult decisions to make about where to focus its
14:08
resources. So what made this the right your
14:11
lead programme, the right programme to take forward?
14:13
What preclinical evidence gave you confidence that it deserved
14:17
to be the the company's lead asset?
14:18
And what are the most important questions you're now looking to
14:21
answer before before entering into the clinic?
14:26
I think for us the selection of DBXO1 as our lead programme as
14:31
primarily strategically driven. So obviously you can ask
14:35
yourself a number of different questions as you build AT cell
14:38
engager portfolio. First, you can ask yourself is
14:41
oncology the correct disease area or should we actually be
14:44
developing T cell engager in different areas And certainly
14:48
the applications in the autoimmune space are becoming
14:51
more and more popular. For us the oncology disease area
14:56
was the choice in particular if we're considering that HLA
15:00
typing is required for our multi peptide MHE targeted approach.
15:04
And HLA typing is certainly something that can be
15:07
incorporated into routine cancer care, but is a lot harder to
15:11
incorporate into sort of the enormous patient populations if
15:15
we're thinking about immune autoimmune diseases or or
15:20
allergies for example. So from a practical
15:24
consideration of making an impact with an HLA restricted
15:27
drug, we felt oncology was the better disease area because of
15:31
the unmet need. You can then ask yourself, are T
15:35
cell engagers the right modality or should we be thinking about
15:38
other modalities? Conceptually, the peptide MHC
15:43
engaging moiety could be transferred into other molecules
15:48
with different business ends. Think about Adcs for example.
15:51
They have the same challenge that they still need to
15:53
recognize cancer cells specifically.
15:56
However, as a proof, we have proof of concept for other
16:00
modalities and we believe there is a modular opportunity for us.
16:05
However, the value proposition of the tumor exclusive target
16:09
recognition is the strongest for T cell engagers because of the
16:14
potency of that modality as a whole.
16:17
Residual target expression on healthy cells can actually be
16:21
navigated for modalities like ADC's.
16:24
So the value proposition that we have with tumor exclusive
16:27
targets is just strongest in the T cell engager space.
16:32
We're then thinking about DBXO1 specifically.
16:35
This is an acid that targets peptides presented in the
16:39
context of H LAAO2 O1, which is the most prevalent allele in the
16:45
world. Therefore that is covering the
16:48
largest potential patient pool and obviously makes this an
16:52
attractive choice from a commercial perspective as well
16:55
as a clinical unmet need perspective.
16:58
And that is why we're focusing on this particular program with
17:01
peptide signatures displayed in AO2O one.
17:04
We do have other pipeline programs that take the multi
17:08
peptide MHC targeting concept into other HLA alleles with
17:12
different geographical distributions across the globe.
17:16
And that will ultimately be an interesting strategic
17:18
partnership opportunity for us. But prioritizing the most
17:22
prevalent allele was important to us as it can pertains to sort
17:27
of patient reach. I would say, obviously we have
17:33
more work to do as we are advancing this program towards
17:36
the clinic and we're currently sort of finalizing the selection
17:39
of our lead molecule and we'll we'll then enter Ind enabling
17:44
studies to confirm the potency and safety of our molecule.
17:50
Nice, that sounds super exciting and looking forward to seeing
17:53
all of that come into into fruition.
17:57
So your role as chief scientific officer, you're I guess you're
18:00
constantly making decisions about where to spend your time,
18:04
where to, you know, use your time for scientific effort,
18:07
money, all of that sort of stuff.
18:09
In an environment where there are always more good ideas and
18:12
resources to pursue them. How do you decide which which
18:15
opportunities are worth back in? Which opportunities are less
18:18
attractive for the company? What principles would guide your
18:21
decision making when balancing scientific curiosity with the
18:25
realities of drug development and and ultimately trying to get
18:29
something to market as well? Yeah.
18:31
I think the the main piece for me would be to think about the
18:36
risks associated with different options that you might be
18:40
pursuing and comparing against each other.
18:43
Where you want to find an appropriate balance of pushing
18:46
the boundaries on behalf of patients and being innovative.
18:51
But at the same time, not assume so much risk, whether that's
18:55
biological risk or otherwise, that ultimately the opportunity
19:00
cost is so high and it takes you too long or it is a too
19:05
expensive approach to ultimately prove out the potential of our
19:11
approach. Obviously as a startup, we first
19:14
have to prove that our hypothesis can actually be
19:17
converted into effective medicines.
19:20
It's one thing to have a creative idea and propose a
19:23
vision, but obviously it has to work.
19:26
And you have to think about how in a most efficient manner you
19:29
get to prove that your approach and your underlying thesis is
19:33
correct. And the more risks you assume
19:36
along the way, in particular, if they're stacked on top of each
19:39
other, then that's that's not a great idea.
19:42
And that's why in in some cases, we are maybe sometimes sticking
19:46
to the simpler, seemingly less creative option than something
19:51
else that was on the table to be compared at.
19:53
But multi peptide MHC targeting is such a differentiated
19:57
approach that we really have to focus on the value of that and
20:01
proving that out The other thing that.
20:06
Bigger picture, I'm thinking about personally because of my
20:11
experience in larger organization, in particular in
20:14
pharma where I really learned portfolio thinking is that
20:21
ultimately this has to not just be our best product or molecule.
20:26
This has to be competitive within the overall picture of
20:30
the standard of care or other innovative ideas to treat the
20:33
same type of disease. And so we have to think about
20:37
what is good enough in the context of the whole
20:41
environment. And so sometimes this is our
20:46
idea and sometimes unfortunately it's someone else's idea and at
20:49
some point we have to understand the trade-offs that we're
20:52
making. But it is it is portfolio
20:55
thinking in a way where multiple biotechs might be the portfolio
21:00
that in the bigger picture is is sometimes driving my decision
21:04
making. Yeah, for sure.
21:08
I think one of the, I guess one of the pressing topics over the
21:13
last few years in biotech is just how difficult it's been.
21:17
It's been a much tougher operating environment over the
21:19
last few years. You know, there's been more
21:21
selective investment, there's been increased scrutiny and
21:25
greater pressure to demonstrate clear differentiation from
21:28
companies, pipelines as well. Just just from your perspective,
21:32
you're obviously working in an early stage company.
21:34
What what have been some of the the biggest challenges being in
21:37
this environment and and how has it changed the way that you
21:39
think about strategy, partnerships or prioritization?
21:44
Yeah. I think the the key observation
21:49
is that the data packages that are required today to secure
21:57
funding or partnerships for early stage companies have
22:01
significantly increased. You are asked for a lot more
22:06
data to to I guess create conviction that an investment
22:12
whether that is through partnership or or pure money in
22:16
the form of of venture capital is well spent.
22:20
And So what that actually means is that your small dollars that
22:25
you start a company with have to create a lot of different types
22:32
of data sets, a lot of value. You don't have a lot of
22:35
opportunities to redo things three times over because that is
22:39
more cost. So there's actually much more
22:43
difficult these days to generate data packages that are
22:46
appropriate in this context. I sometimes find it frustrating
22:51
that the kinds of data sets that are on a regulatory path or that
22:56
actually are scientifically sound are not necessarily the
23:01
identical data sets that investors or often even pharma
23:05
companies are requesting. And so it is often a trade off.
23:11
Where do we invest our our money?
23:14
In which experiments should we should we be investing our
23:19
resources? Because ultimately it doesn't
23:21
help us to progress on the regulatory path if we can't
23:25
secure funding or partnerships along the way.
23:28
So at some point you sort of have to play the game.
23:31
I'm going to say I don't mean that in a negative way.
23:34
Everyone has their reasons why they're looking for specific
23:37
data sets, but I wish that we had a little bit more
23:41
flexibility sometimes to follow the clear scientific path that
23:45
you should be taking. But ultimately you do have to
23:49
play to your stakeholders. That would be the same within a
23:53
larger organization for us the the stakeholders to work with
23:58
our investors and and pharma partners.
24:01
Yeah, for sure. And so as you look ahead over
24:04
the next 12 to 24 months, what would you see as the sort of key
24:08
inflection points for debt bio, you know whether on a funding
24:12
partnership, scientific readouts?
24:15
Just talk us through what the next major milestones that you
24:18
guys are most excited about. Yeah.
24:21
The nearest term milestones is development candidate nomination
24:25
for lead asset DBXL1, which then really kicks off manufacturing
24:30
as well as I and D enabling studies ultimately leading us to
24:35
enter the clinic in early 2028, which obviously will be a major
24:40
milestone for the company and provides us with the opportunity
24:44
to test out our our hypothesis in in patients in between there.
24:49
I do believe that a fundraise closure or a pharma partnership
24:53
will be another important milestone that we need to reach
24:57
in part to fund our path to the clinic, but also because it will
25:03
allow us to build the company out.
25:06
We intend to do that in a modest way, but yet there are obviously
25:10
line functions that we need to add to the existing team as we
25:14
are getting closer to to the clinic.
25:17
Ideally this would be combined with a follow on program and a
25:20
development candidate nominated for that within the next two
25:23
years or so. But our immediate focus is
25:27
definitely on DBXO1 and driving that to the clinic in the most
25:30
efficient manner. Yeah, sounds exciting.
25:34
And this is a question that we would always finish with as
25:37
well. Yeah.
25:39
If you were to sit down and have dinner with any free people from
25:42
past or present, who would you choose and why?
25:44
It doesn't necessarily need to be people from the industry,
25:47
although it it can be if you like.
25:49
But yeah, free people you'd like to sit down and and have a
25:52
dinner with. Yeah, that is a fantastic
25:54
question. My very clear #1 dinner guest
26:00
would be Doctor Brené Brown. She's a social worker turned
26:05
qualitative researcher. She studies a number of
26:10
different qualities, including vulnerability and shame.
26:13
She has one of the most popular Ted talks ever on vulnerability.
26:18
She works in leadership, helps company transformations.
26:24
And it would just be fascinating to sit down with her and and
26:27
talk about her work but also her love for sports which I share.
26:34
The 2nd guest would be my late grandmother.
26:38
She is the matriarch of our family and has pulled a lot of
26:44
different personalities together within our family.
26:48
And I would love to continue a few conversations that I didn't
26:51
get to finish when she passed away.
26:55
And I think my third choice might be Sean McVeigh.
27:01
He's the current head coach of the Los Angeles Rams.
27:05
In fact, he is known to be the youngest head coach to ever
27:09
reach and win the Super Bowl at 36, which is actually six years
27:14
younger than Jose Mourinho when he won the Premier League as as
27:18
the youngest coach there. And I would love to have a
27:22
conversation with him about how you establish trust at that
27:27
young age, having been the youngest individual or at least
27:30
felt like the youngest individual in a lot of rooms.
27:34
I I would love to pick his brain about how how he does that and
27:39
how he creates high performing teams.
27:42
Yeah, well, I love all of those 3 answers for sure.
27:46
And thanks so much again for coming on and helping us out
27:48
with this. It sounds super exciting what
27:50
you guys are building at Deck Bio.
27:52
I'm looking forward to seeing the next inflection points, as
27:55
you mentioned over the coming months and years and for sure a
27:59
company I'll be keeping out my eye out on.
28:01
So Joanna, it was an absolute pleasure to to have you on and
28:04
and thanks again for for sharing your story and and deck bio
28:08
story so far. Thank you.
28:09
Thank you for having me on and giving me the opportunity to
28:12
talk about Deck Bio. I really appreciate it.