September 28, 2024 • 41 mins
Iain Kilty, CEO of Sitryx, shares his insights about leadership in biopharma and how Sitryx is working to alter immune cell metabolism to resolve disease
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
John Simboli (00:00):
Today I'm speaking with Iain Kilty, CEO of Sitryx
(00:03):
therapeutics, headquartered inOxford, UK. Welcome to BioBoss,
Iain.
Iain Kilty (00:09):
Thanks, John. I'm looking forward to the
conversation.
John Simboli (00:12):
Iain, what led to your role as CEO at Sitryx?
Iain Kilty (00:15):
So I took on the role relatively recently,
actually just a couple of monthsago, but I've been working with
Sitryx for just over the lastthree years. I was the CSO
before transitioning into theCEO role, and it was a great
opportunity for me to lead acompany that I'm passionate
about and really believe that wehave a chance to have a huge
impact on patients who sufferfrom autoimmune diseases. And
(00:38):
that's really been the area I'vespent my whole career in
different guises. So prior toSitryx, I was working in
Cambridge Mass actually, withAtlas venture, as a CSO for one
of their immunology companies,but also as an entrepreneur in
residence, helping them seed newcompanies in that space. But
spent the bulk of my careeractually at Pfizer. I was at
(00:58):
Pfizer over 20 years, both USand UK, always in the immunology
space, but a variety of roles,from leading early target
discovery teams through toleading clinical clusters in
rheumatology and dermatology,before ultimately being
responsible for theirpreclinical portfolio in INI.
And as part of that role,actually, I was doing a lot of
(01:19):
work, working with biotech, andwhilst, I guess lots of
fantastic things about BigPharma and Pfizer and had an
amazing time there, learnt ahuge amount, had the opportunity
to contribute to marketedtherapies now, but the dynamism,
the opportunity to impactthings, to really drive programs
at speed and take risks was wasmore available to me in the
(01:43):
biotech world, and I've reallyenjoyed making that transition.
John Simboli (01:48):
What's it like to be a CSO and then become a CEO?
What sorts of understandings doyou have now? I know you're in
the job relatively a short time,but what's it like to be a CSO
versus what's like to be CEO?
Iain Kilty (02:01):
Yeah, so it's, as you say, relatively early in my
CEO experience, but the previousCEO actually is chap called Neil
Weir. He was the CEO from thestart of Sitryx, and when the
company was founded, and he'sstill within the company, he's
now president of the company.
Which is great for me, becauseNeil's been a mentor all the way
for me since I joined Sitryx,and this was part of a
(02:22):
succession planning it was evendiscussed as I very first joined
as the CSO. And obviously, as aCSO, you're primarily focused on
driving that scientificportfolio. And I joined at a
time the company was reallyevolving from having some early
targets to driving those targetstowards development candidates
and needing to become more of aprofessional drug discovery or
(02:43):
drug development organization,which was a huge amount of fun,
and we've now been able todeliver multiple programs
through those stage gates. Sowith respect to the transition
of role over this time, Neil'sgiven me opportunities to be
heavily involved in the investordiscussions, the pitches, the
strategic thinking of thecompany and so on. So it's less
(03:04):
of an abrupt you're thescientist. Oh, now I want you to
be involved in all of theseother things than a transition
over time, which has been greatbecause, obviously I know the
company very well. It's not likecoming in as a CEO and trying
and learning the science,learning the strategy and so on.
I've been involved in buildingthe company to this point, and
that was one of the reasons thiswas a really exciting
(03:26):
opportunity for me. Because Isaid earlier, I think I have
great belief that we have achance to really make a
difference for patients in whatwe're doing. I really like the
team, and I think we have somereally quite exciting assets to
take forward to the clinic now.
The key thing even in theseearly days, is my focus is
moving away from that managementof that scientific portfolio on
(03:48):
a day to day basis to all theother pieces, thinking about the
discussions with the bankers,the discussions with lawyers
working with the board, andthat's an interesting reporting
relationship that's new for me,I've always had a direct boss,
and whilst I report into thechair of the board, Pierre
Legault, and he's been also agreat mentor for me, you have
(04:09):
lots of other players on theboard as well who are from
different institutions,different organizations that
you're working with. So hugeamounts for me to learn on that
front, lots of connections, lotsof talking to people and a lso
important for me within theSitryx organization, that it's
not just the science part of theorganization that feels they
know Iain. Now we're smallenough for 45 people that I knew
(04:32):
everyone anyway, but it's adifferent relationship now to
make sure I'm interacting withthe finance team and in a
different way, the operationsteam and so on and so forth. So
yeah, lost lots to learn, butit's a transition more than any
sort of revolution in the wayI'm doing things
John Simboli (04:49):
From early on in your in your career, your 25
years with Pfizer, did youpicture at some point being a
CEO? Or is this something thatsort of evolves as time goes
along?
Iain Kilty (05:00):
Yeah, so when I was at Pfizer, I don't think I
necessarily pictured myself asbeing a CEO. I think actually,
as I developed in my career atPfizer, I would take on new
levels of responsibility andalways enjoy it, and once you
got comfortable with that, you'dlook at the next role and think,
well, I could have more impactin that next role. And then look
for those opportunities to buildout my toolkit, build out my
(05:21):
experiences to be in a positionto take on those next roles. And
as I mentioned earlier, actuallyI spent a bit of time in the
clinical phase of drug discoverywhile I was at Pfizer, which was
not my initial background. I wasPhD scientist, very much lab
based early on in my career, butreally research focused. But
(05:42):
that experience for those fewyears was hugely impactful in
how I then did my job leading aportfolio through to
development, candidate,nomination and early, early
development, So phase one, 1btype work. So in a similar guise
as I talked about, I wasinteracting quite a bit with
biotech companies when I was atPfizer, and that's what really
(06:02):
fired my interest, that adynamic place to work. I could
really try and influence things.
I felt I could bring experiencefrom big pharma into that
biotech setting and add value.
And to me, that's one of themost important things. Am I able
to add value here and reallyprogress towards making drugs?
Because fundamentally, that'swhat I want to do. I want to
make drugs that change people'slives. And there's no feeling
(06:24):
quite like being involved in aprogram that you get the first
clinical data and you see it'sworking, and you think I was
involved in that. That was anidea that we had on a PowerPoint
slide and so on. So that drovemy transition into a biotech and
CSO was the obvious area foreven my scientific background.
But in a similar guise, my firstCEO, I worked with a lady called
(06:44):
Sam Truex at Quench Bio, who's agood friend, and again, another
great mentor. I've been reallylucky with the people I've
interacted and worked withthrough the years. And there
were lots of elements of whatSam was doing that she gave me
the opportunity to learn about.
And I thought, well, there'sareas here that I think I could
really help too, because I bringa different style, I bring a
different way of thinking. Andeven then, I wouldn't say I was
(07:07):
100% sure that my next goal isto be CEO, but I certainly felt
there were areas where I thoughtI could bring value again as a
CEO with a slightly differentbackground. Sam's background was
more business development than acore science and so on. So
joining Sitryx was similar andcoming in as CSO, not
necessarily absolutely settingmy heart on CEO at all, but, but
(07:30):
it really felt like there was anopportunity here, given what
I've already described throughthe transition with Neil moving
into a role as president and soon for me to take that next
step. And I really do enjoy thebusiness side of biotech as well
as the scientific side. And Ithink it's you bringing those
(07:51):
two pieces together that giveyou the best opportunity to
deliver those new drugs forpatients. And another quick
comment, some of the exposurethat I've had on that business
side has also come through myentrepreneur in residence role
at Atlas, and I'm a venturepartner with SV health investors
right now in London, and thosethings, you start to see those
(08:12):
elements of the job. And again,felt, well, I think there's
value I can add. I've gotexperience pre clinically, and
clinically, the company's movingto more of a clinical phase now,
and it's the next step indevelopment for me, and
hopefully I will be able to addreal value to Sitryx.
John Simboli (08:30):
I want to ask you about the leap of faith part of
this. You were well prepared, asI've understood what you just
told me, and it's quite logicalin some ways, in most ways, to
follow that path that youfollow. On the other hand, there
is, I would say, probably, formost people I've spoken with,
there is a leap of faith aboutgoing from something that's very
big, like Pfizer or BMS orwherever it might be, to
(08:53):
something that's new and gettingstarted. And I remember a
conversation with two founderswho, one co founder spoke to the
other and said, I'm thinkingabout starting this company,
would you like to join me? Theother guy said yeah, and they
were both really excited as theytold me the story, and then they
said, then we went home and toldour wives. So that's the part of
the question I want to ask youabout when you come to grips
with that, this is exciting, butthis is an unknown. How does one
(09:16):
negotiate that?
Iain Kilty (09:17):
Well, you're absolutely right, and you've
been in the environment, in BigPharma, but you've been
reasonably successful. It'sreasonably comfortable. You're
well compensated, and you'vealso, you've got teams you
really like, generally, I didanyway, that's the hardest
piece, in many respects, wasleaving some of the people.
You're also leaving value on thetable, because you have various
options and all the rest of it.
So it is an element of leap offaith. It was interesting. I
(09:40):
didn't need to go back to mywife and sell this. She knew
that I was really ready to go,probably before I did, in some
respects, because she could seehow energized I was when I was
working with those biotechteams, through some of the work
I was doing for Pfizer at thetime, and how I'd come back and
talk about it and the receptionsI'd been. And chatting to those
guys, and I obviously discussed,I think I could, I could have an
(10:03):
impact, that I could, I could dosomething that's valuable. And
she, she was very encouraging,actually, well, if you believe
it, just go, you should do it,which was fantastic. It's
fantastic to have that sort ofsupport at home, because yeah
there's definitely anervousness, and it's really
interesting because one of thethings I was most nervous about,
actually, was job securitymoving into a small company. I
was the fourth employee atQuench Bio when I moved there,
(10:26):
so it was a small company at thetime. But I'm not sure that
actually, now I've been in thatworld for a number of years, I
don't think that's really theright thing to be concerned
about, because the reality isthat with any of these, with any
of these investor ecosystems, ifyou do a good job within that
ecosystem, there's always needfor people with experience and
drive to join other startupcompanies or establish biotechs.
(10:50):
There's no shortage of roles.
Now, your company name maychange more than it would at a
Pfizer and so on, but, but Ijust don't think actually
there's that there's such a bigdifference in job security. It's
just a different type ofsecurity, as long as you could
deliver. And I guess then theother piece that you always
have, and you have as you step,well, I have as you step, from a
CSO into a CEO role, is there'salways an element of, you know,
(11:14):
can I, can I do thiseffectively? You know, there's
always a bit of impostersyndrome. And mind you, those
sort of things, you know thatthose things keep you sharp,
keep you focused, make you workhard, so I think that's just all
part of the process.
John Simboli (11:27):
So here's a related question about how
people think of a CEO ascompared to another C suite job.
So I spoke with a person who wasthe Chief Business Officer at a
biopharma company. And he toldme that he was accustomed to
going into the meetings with CEOand the other members of the
(11:47):
team and posing options, youknow, we could do this. We could
do this. And then he said, whenhe became CEO, he just without
even understanding that he washe was doing that, he was
explaining to his team we coulddo this and this. And he said
frequently, suddenly they wouldturn to him and surprise, he was
surprised by this, and turn tohim and say, yeah, but which one
(12:07):
are we going to do? So there isa collaborative aspect, but
there's also an expectation,right, that the CEO will be a
final decider. So again,probably early in the cycle,
maybe I should ask you this insix months, but do people look
at you any differently as theCEO than they did as the CSO
internally?
Iain Kilty (12:26):
I think so. I mean, my natural style is I do like to
make decisions. And we've donevarious analyzes with our LT,
you know, all the differentHogan type analyzes and things
to look at our different stylesand I'm probably the strongest
decision maker style within theteam. So that piece is quite
natural for me, and I quiteenjoy that, being able to make a
(12:48):
decision and move on. I like tomake a decision before we leave
the room. But yeah, obviously Ilike to listen to the team and
so on. Now, as a relativelyearly stage biotech just moving
our first wholly owned programto the clinic now, a lot of what
we're talking about is in myarea of expertise, because it's
the drug discovery piece. So Ifeel comfortable around that
(13:08):
drug discovery development. Itgets a bit more tricky if you're
talking about decisions you needto make around a legal decision
or a decision about some thingswe've been talking about
recently, the lease and labspace we might want versus not,
and some of those things. Soyes. So I think as you move more
out of your comfort zone, thosesort of decisions get harder,
(13:29):
don't they? Now what's great isI have a really good leadership
team who I can rely on to adviseme and to be involved in that
debate around any of those sortsof decisions that need to be
made. But yeah, no doubtthere'll be challenges in the
future in that way. I thinkactually, one of the things I've
(13:49):
already seen is just peopletreat you differently once
you're the CEO, because you'renot quite a peer anymore. And
some of those, you know, much ofthe team, it's many of the team
were my peers previously. Andwhilst you don't, I don't
personally feel any different.
You do notice the style ofpeople's interaction can be
subtly different. And I thinkyou just have to get used to
that, that you know you're in aslightly different position.
John Simboli (14:11):
When you first came to Sitryx, do you recall
what it was in particular aboutthe science that grabbed hold
you? I'm sure you looked athundreds of other options and
possibilities at that timecoming from Atlas, you saw many
different things, I'm certain.
So my question is, do you recallwhat it was specifically about
Sitryx that made you say, Ireally want to investigate this?
Iain Kilty (14:31):
Yeah so there's, there's a few elements to it,
actually. So I had theprivilege, again, working at
Pfizer, to work on particularlyjak kinase inhibitors, which
have become drugs and otherprograms which have really had
an impact on patients, which isgreat. The way that those
approaches work is that they'resuppressing elements of the
(14:52):
immune system, and from thereyou can drive a certain level of
disease remission, but we kindof got stuck with the amount of
disease remission we can achievein rheumatoid arthritis, in
inflammatory bowel disease andother indications. So we need to
start thinking slightlydifferently about how can we
really move that needle to drivegreater therapeutic benefit for
(15:13):
patients and drive morepatients, as I say, into true
remission and sustainedremission at that. So actually,
when I was at Pfizer, we werelooking at different areas we
could invest in to do that. Andone of the areas we felt really
had that potential wasimmunometabolism. So we actually
had a group there, when I was atPfizer, focused in this space.
(15:34):
It was a space I knew prettywell. And the fundamental thesis
for immunometabolism is that bymodulating the metabolic pathway
cells are depending upon, youcan modulate the phenotype of
those cells. So you can move acell from in effect, a pro
inflammatory cell, to more of aregulatory or homeostatic sort
of type cell, and that has thepotential to really drive much
(15:57):
greater efficacy for patients.
So the disease area wasinteresting to me. I think the
other elements were, it's asmall molecule company. I've got
a lot of experience in thatspace. And going back to the
point I made about, do I think Ican make a difference in that
organization and really addbenefit? And then,
fundamentally, it's superimportant it's the right team.
(16:17):
And when I met previous CEO,Neil, Neil Weir, and some of the
other leadership team at thetime, I really felt that this is
a team that would be fun to workwith, but know what they're
doing and have a clear vision ofwhere they want to go. And
equally, we have a greatinvestor base, and that's also
incredibly important, as youknow, in the biotech world,
(16:37):
seasoned investors who reallyunderstand drug discovery and
development and I had theopportunity to meet with a
number of the investors as wellbefore I took the role and and
again, was really encouragedthat they would be great people
to work with. So it was amixture of the science made
sense to me, I already knew someelements of it, the team were
great and the investor base wasgood.
John Simboli (17:02):
When you tell someone who's from outside the
industry that you're the CEO ofSitryx therapeutics, what do you
think they picture you doing allday, and what do you do all day
when you try to explain to them,no, I do this.
Iain Kilty (17:15):
So usually, if I'm asked, what do I do for a
living? I would say, well, Iwork in a company where we're
trying to make new drugs to helppeople with autoimmune diseases,
diseases like arthritis andinflammatory bowel disease,
eczema and so on. And thenpeople have usually got a
reference point there that theyknow somebody who who struggles
with one of those diseases. Andthen perhaps, if that piece is
(17:37):
clear, and they say, oh no, Iunderstand that. But, is it
pharma biotech, then I wouldjump in and say, well, I built a
lot of my experience and skillset working in Big Pharma, but
now I work in biotech and enjoyworking there because of the
dynamic nature of that business.
But it's an ecosystem. Bigbiotech needs Big Pharma. Big
Pharma needs biotech, so westill work closely with pharma
(17:59):
and spends a lot of time withthose teams. And then to what do
I specifically do there? Well,I'm a scientist at heart. I'm
focused on developing drugsthat'll change people's lives,
and perhaps tell them a bitabout our lead programs in
eczema. A lot of people knoweczema, and so you know this,
this, it's a small molecule,it'll be it's a pill. If it
(18:21):
works people, it'll really helpthose people with more severe
disease. So, so trying to findthose reference points that make
sense to people.
John Simboli (18:30):
Can you recall when you were eight or nine or
10 or some formative stage andyou were thinking, my parents,
this is as a kid, of course, myparents think I should become a
kind of connected to, gee, I'minterested in this. Does any of
that have anything to do withhow your professional life
played out?
Iain Kilty (18:46):
It certainly does, to a degree. I think my parents
and probably even I as a child,always knew I'd be involved in
the sciences somewhere. I was asort of kid who asked the why
question all the time. I wantedto take things apart, understand
how they worked. I used to loveall the sciences, actually, so I
didn't know which path I wouldfollow. Would it be physics,
chemistry, biology? It alwaysfelt like it was going to be
(19:10):
something in one of the in oneof those directions, because
that was what fired me up as achild, reading about nature,
being out in nature. I grew upin Cumbria in the northwest of
the UK, and it's a stunningarea. It's right by the net Lake
District National Park. So usedto spend lots of time out in the
Fells and so on there and thatused to really inspire me, that
the again, just being in natureand trying to understand it,
(19:33):
geography also. So did I knowI'd be in a biotech company? I
probably wouldn't have knownwhat a biotech company was at
that time. But did I think I'dbe doing something scientific?
Probably, that's probably what Iwould have told you. I want to
be a scientist or a doctor orsomething that has a link to
science. But yeah.
John Simboli (19:54):
Do you recall at a later stage, when you were in at
university or in medicaltraining, whatever's the
appropriate part for thisquestion, can you remember,
yeah, that's exactly the part ofit that I want to investigate.
Maybe, as a professor, maybe itwas an idea that, yeah.
Iain Kilty (20:11):
Yeah, so I actually, I did my first degree in
Cambridge in the UK. And thescientific degree you enter
Cambridge in is called naturalsciences. So it starts quite
broad, and I actually enteredthinking I'd be a chemist. So my
first year, I was thirdchemistry, third molecular work,
(20:31):
molecular biology, and then athird sort of zoology type work.
But it was really with a view tochemistry and moving forward.
But actually, once I got there,I got really inspired at an
electrical Bruce Ponder, he wasone of the guys who identified
the BRCA gene mutation in breastcancer. And I remember he, I
still remember when he gave atalk about this, and I thought,
(20:53):
this is amazing. This isactually the world I want to go
into at that point, because thisis changing people's lives. He's
worked out one of the causes of,you know, familial breast
cancer. So it was fascinating.
And really it was the influenceof people like him that that
moved me from the chemistryfocused more towards a molecular
biology and biochemistry. And aspart of that, I did pharmacology
(21:15):
work and so on. I think theother thing that made me think
is, I'm probably not a long termacademic. I really want to think
more about the applied nature ofthis medical research or
scientific research, and then itjust, it really just evolved
from there, went on to a PhD andthen into an industrial postdoc
(21:37):
after that.
John Simboli (21:42):
If someone says, who is Sitryx therapeutics, how
do you like to answer that?
Iain Kilty (21:45):
Yes, Sitryx therapeutics are an immunology
focused company, but withinimmunology, we're exploiting
immunometabolism to drive agreater anti inflammatory
response in chronic, autoimmuneand auto inflammatory diseases.
The real potential here is thisfundamental thesis around
immunometabolism, that bymodulating metabolic pathways,
(22:07):
we can reset the phenotype ofinflammatory cells, so we're not
blocking a single pathway or asingle cytokine. We're moving
the cell to more of a noninflammatory cell type, so
that's not immunosuppressive. Sothat's quite different to
current anti inflammatorytherapies, and we think offers
that potential to drive muchgreater efficacy for patients.
(22:29):
It's a company that was foundedby a number of the leaders in
the immuno metabolism space. Oneof our founders, Luke O'Neill,
has really driven a lot of theliterature. Jeff Rathmell, Mike
Rosenblum, Jonathan Powell, allgreat scientists working in the
field, and that's given us agreat basis in scientific
knowledge. And then what we'vedone is combine that with a team
who've got both big pharma andbiotech experience, certainly
(22:52):
within the leadership team, sothey know what good looks like,
but they can also work nimbly tothen be able to exploit that
science and deliver noveltherapies to the clinic.
John Simboli (23:02):
Is there a way to talk about the mechanism of
action for the lead candidatefor the eczema candidate that
you'd like to talk about?
Iain Kilty (23:10):
Yeah, so our LEAD program is a PKM2 activator
program. So PKM2 is an enzymethat's involved in glycolysis.
It's been a well characterizedenzyme for a number of years,
but about a decade or so ago, itwas shown that as well as this
role in glycolysis, this enzymehas a moonlighting role
regulating gene transcriptionwithin the nucleus of cells. And
(23:33):
the way it regulates whetherit's driving glycolysis or
driving gene transcription iswhether it exists as a dimer or
a tetramer, so it says anequilibrium between the two in
cells, and the dimer will drivethe nuclear pro inflammatory
gene transcription. The tetramerwill drive glycolysis. So our
small molecules induce formationof that tetramer, so skew you
(23:55):
away from that nuclear activityand maintain that metabolic
activity. And the net effect ofthat is you could, you reduce,
particularly lymphocyte T and B,lymphocyte proliferation,
cytokine production and antibodyproduction.
John Simboli (24:11):
How do you see the lead candidate in terms of your
vision for the portfolio as awhole? Where does it fit in?
Iain Kilty (24:19):
So our lead candidate has helped us really
build our understanding of howto prosecute immunometabolic
targets. And one of the things Ihaven't really touched on yet,
but is absolutely critical inprosecuting this target class,
is looking at cells in theappropriate cellular context.
And what I mean by that is, ifyou're growing cells in media
with lots of glucose, aminoacids, oxygen and so on, that's
(24:43):
designed to keep cells alive.
That's nothing like aninflammatory site where the
cells are competing with eachother for all of those things,
amino acids, glucose, and it'soften hypoxic and so on. So if
you really want to reveal thepharmacology of modulating
metabolic pathways, you need tomodulate the environment the
cell is in and build confidencethat's relevant to the
(25:04):
inflammatory state in disease tounderstand the pharmacology. Now
our lead program is a greatexample of that where the
pharmacology is only revealedunder conditions where the cells
have depleted extracellularserines, the amino acid serine,
and then what happens is cellsneed to make their own serine.
Under those conditions, they upregulate this serine
(25:24):
biosynthesis pathway. That'swhen you see the pharmacology of
PKM2 activators in T lymphocytesand B lymphocytes. So there's a
lot of reasons that's exciting,because that means you've got a
very laser targeted approach toit sites where serine is being
used up, not just in the blood,where you'll have high levels of
serine, but at thoseinflammatory sites where you're
getting competition. But it alsoprovides, if you'd like, an
(25:48):
initial way to think about anynew target that we bring in. So
not every target is going to bedependent on serine. Other
targets are going to bedependent on other mediators,
and they may be relevant todifferent situations. So those
sort of insights have beenimportant in how we've then
prosecuted the future portfoliobeyond PKM2. But I say we're
very excited about PKM2. There'sclear medical need in eczema,
(26:12):
and a small molecule, once ortwice a day pill that could
really drive efficacy for thosepatients in a safe manner would
be hugely beneficial.
John Simboli (26:23):
Sometimes, when I talk with folks on BioBoss, I
find the discussion is largelyaround the scientific puzzle,
how do I unravel this? How do Imake sense of this? How does our
company move this forward? Andthen other times, the discussion
will also include, if this worksthe way I think it will I can't
wait, because I can see how thiscould have an effect on
(26:44):
patients. And of course, the twoare intertwined. You couldn't do
one without the other. Butthere's like a shifting thing
that happens over time in myexperience. So where are you on
that process? Are you, are youfocused primarily on
understanding how this all maywork. Do you also allow yourself
to think about, jeez if thisworks this is going to really do
(27:05):
some good for some people.
Iain Kilty (27:07):
Yeah, absolutely allow myself to think the
latter. I think that's the thingthat makes you jump out of bed
in the morning. So if I didn'tbelieve it had that potential, I
wouldn't be as excited about it.
I think the potential here isthat we can really drive a shift
in immune cell phenotype fromdriving inflammation to more of
a homeostatic or noninflammatory regulatory
(27:29):
phenotype, and that has thepotential to drive sustained
remission for patients whichwhich would be huge. Our lead
program is focused on eczema,although we do think this asset
could have value acrossadditional indications, and
there's clear medical need therethat there's a real breakthrough
a number of years ago whendupilumab dupixent was approved.
It's a biologic that modulatesL413. But that that drug, about
(27:51):
50% of the patients get a 75%improvement. So that's similar
to an anti TNF in psoriasis. Sosignificant, makes a huge
difference to patients, butthere's a lot of medical need
remaining, and the next wave ofcompounds were Jak inhibitors. I
worked on some of those when Iwas at Pfizer. One of those is
now an approved drug, which isgreat, and they do give slightly
more efficacy because theyintegrate more pathways than
(28:13):
that 413 pathway But there aresome limitations around the
label and the safety of thoseassets. So if we could achieve
efficacy similar or better, butwith a much safer therapy, that
for patients would be have ahuge impact, and that's what
makes me jump out of bed in themorning. I think we have some
really nice data to say thatthat may well happen, but we've
(28:33):
got to generate the clinicaldata to say, is that true? But I
truly think that that isexciting.
John Simboli (28:40):
Do you see that as a potentially incremental change
for patients? As somethinggreater than that? It's going to
vary from patient to patient,but.
Iain Kilty (28:49):
I think it has the potential to be greater than
that. I think it will vary frompatient to patient, which is
nearly always the case. Alwaysgets some really good responders
and some people who are notresponding as well to the
therapy. But just because ofheterogeneity within the
disease, but also, there's ahuge element of convenience here
for patients to be able to takea pill on a day to day basis, as
(29:10):
opposed to a two weeklyinjection. I think for a lot of
patients it'll increase accessas well. More patients will
actually be able to get hold ofthat drug, I would hope, and
therefore get that benefit.
John Simboli (29:21):
When you tell the story about Sitryx and people
get it wrong, do you ever see apattern about why they're
getting it wrong, even thoughyou said it a different way,
they heard it a different way,and then you can help them to
get back on track. Another wayof saying this, how might people
misperceive what Sitryx isabout?
Iain Kilty (29:39):
Yeah. So I think the biggest misperception we see is
actually more on the safety sideof things, if you're interfering
with metabolism. So gettingpeople comfortable that we're
not interfering with fundamentalelectron transport, chain type
metabolism. What we're focusingon are those metabolic changes
(29:59):
we're seeing at inflammatorysites, those cysts, those
pathways which upregulated tomake a TH17 cell more active or
or a macrophage produce morecytokines and so on, and to
really helping people tounderstand that by targeting
specific enzymes whichupregulated at those sites, but
also the importance of cellularcontext that we talked about
(30:22):
earlier will drive a veryfocused pharmacological effect.
So it's not a broad effect thatyou'll see across all tissues,
and that tends to be a placewhere people can, yeah, they
come in, possibly with a biasthat I can't see how you could
do this in a safe manner. Now,the nice thing we can do now is
(30:42):
that we have a program that Lilyopted into at IND last year. So
we show that we can generategood margins through GLP talks,
which gives you some confidencethat this isn't a type of
approach which can never besafe. And now our lead program
is at a similar stage withinSitryx, our wholly owned
program, as well, where, again,we've shown good margins through
(31:04):
GLP talk studies. Which so Ithink as we build that data set,
people will get more comfortablewith that. But conceptually,
that can be a challenge earlyon.
John Simboli (31:12):
For the people who like the devil's advocate
approach, sometimes the questionfor the CEO becomes, well,
that's a great idea, but if it'ssuch a great idea, how come
nobody else did it? So I'm sureyou get variations on that from
time to time. What's the bestanswer for that?
Iain Kilty (31:27):
Well, I think the science is evolving all of the
time, and people actually havefocused on immuno metabolism in
cancer in the past, whichactually has been a good source
of targets and certainly toolcompounds for us to validate
mechanisms and pathways, and ithasn't necessarily been the most
efficacious therapy in cancer,but you're trying to do
something very different incancer. In cancer, you're trying
to block a pathway to kill acell. What we're doing is
(31:49):
blocking a pathway to driverewiring of the pathway to
different metabolic pathwayswithin the cell and changing the
phenotype of the cell. Andthat's actually what was seen in
some of some of the oncologystudies. So we've learned from
the oncology studies, and thenapplied that to immunology. So I
think it's actually reflectiveof the evolving science, and
that we're part of the firstwave there. And then I'd go back
(32:11):
to again, that we just havegreat founders who are a number
of the leaders in the field thathave helped us move at speed.
And we continue to work reallyclosely with particularly Luke
O'Neill and Mike Rosenblum forcompletely different things,
actually, but work closely withthose guys as we drive forward
our portfolio.
John Simboli (32:29):
Who makes a good partner to Sitryx therapeutics?
Iain Kilty (32:32):
We're really lucky, actually. We have some fantastic
partners at different levels. Sogoing to some of our founders,
academic partners, I'vementioned Professor Luke O'Neill
a couple of times from TrinityCollege, we have a postdoc in
his lab, but we have joint labmeetings with with Luke, and a
really open dialog. And I thinkthat really helps us, because
that keeps us at the cuttingedge of the academic science in
(32:52):
this space, and also helps, fromhis side, he learns more about
the pharmacology, and we'regetting great tools, which he
can then use in his science. Sothere's joint benefit there. But
the other really goodpartnership we have is with Eli
Lilly. So we signed that deal,actually just before I joined
Sitryx, and they've worked withus on a number of programs. They
(33:13):
opted into one of our programslast year that was IMD, which
they now fully run, and it's inphase one development. And we
have a second program we'reworking on with those guys. And
the way that works so well,actually, is that we just,
again, we have joint projectteams. It's really open between
the two companies, and we bringdifferent skills to the table.
So we own the strategy atSitryx, but it's hugely helpful
(33:37):
to be able to pull on theknowledge of the Lilly team and
ensure that we're fully alignedas we're moving things forward.
The last thing we want to do isprovide a package that doesn't
align with their needs. Andthey're very good as well.
They're not, certainly notobliged to, but they do help
generate various data fromdatabases they can access that
we can't, that help us moveforward more efficiently. So I
think the similarity in bothcases is that openness. I'm
(33:59):
really trying to work as oneteam with a common goal. The
science has to be good. If ascience isn't good, then doesn't
matter if you put the best teamin the world in it, you won't
deliver drugs. But you can havegreat science with a team that's
not functional, and you're notgoing to get there either. And I
think the culture that's beenbuilt at Sitryx has really
enabled the company to moverapidly to the point we are
(34:20):
today, and it's just a fun placeto work for those reasons. And I
think, as well, has facilitatedthis close collaboration, with a
couple of examples I was givingyou earlier, around the academic
collaborations and theindustrial collaborations.
John Simboli (34:34):
If I were to ask people on your immediate team,
you know, what's Iain'smanagement approach, how do you
think they would answer there?
Iain Kilty (34:41):
Yeah so, I think they would answer that I'm
approachable and very calm. I'vealways been told I'm a very calm
person, which is great. Like tolisten to everybody's views, but
I really do like to have adecision made. It doesn't always
have to be my decision. I justdon't like leaving a room
without a clear plan. And Ithink they would probably
reflect that ss well in theirfeedback. And I'd certainly
(35:03):
hope, as I said, that they wouldfeel that I'm accessible and
they can chat to me. And there'scertainly elements of evidence
for that that I take comfortfrom, that that's true. You get
bits of feedback, but as we wentthrough the transition, a number
of those quite junior teammembers would come and chat to
me about, oh, if in this newrole, will I still have chance
to ask you about this, and can Ishare these thoughts or whatever
(35:23):
it might be? And I was reallypleased that people were willing
to come and take some time withme to talk about any concerns
they had about any changeswithin the company.
John Simboli (35:33):
How do you know when it's time to make a
decision versus when it's timeto look for more information?
Iain Kilty (35:39):
Yeah, it's a great question, especially in
research, because I don't thinkyou ever really know, are you at
60% of the information? Have Igot 90 or actually 20? How far
do I need to go? So a lot ofthis, I think, comes from some
experience, and also just theimportance of the decision and
the impact of the decision. Soif this is a relatively small
(36:00):
decision, it's $5,000 to bespent on study x, or whatever it
might be, then I think you canbe pretty comfortable making
those decisions with relativelysmall amounts of information. If
the decision really could impactthe future of the company and
the direction you're going togo, and maybe something you
couldn't easily undo, then youreally need to make sure you've
(36:21):
done as much diligence as youcan. But I do think one of the
things from my experience inboth big pharma and biotech,
that if you get into a placewhere you can't make a decision,
then you're in trouble, becauseyou've almost made a decision by
not making it, you're juststatic, and if you're not moving
forward, you're movingbackwards. So I think you've
obviously got to be careful.
You're not ready fire aim. Youneed to give yourself chance to
(36:45):
have really thought thingsthrough and had the appropriate
diligence around a decision thatyou make. But it can be
comfortable sometimes,especially for the more
difficult decisions to say,okay, let's get back together in
two more weeks, and we'll doresearch X and come back to this
decision. So I just think, youknow, you have to be careful,
because you've, you've actuallymade a default decision there.
John Simboli (37:06):
Is anything about the origin story and the
community that is there inOxford and in UK in general,
that would be interesting foryou, in your opinion, to talk
about?
Iain Kilty (37:19):
Well actually I was in Cambridge, Mass for 10 years
before I took this job, so thatwas quite a different
environment. So first I cancomment on that. So I originally
was in biotech, working withAtlas venture in tech square in
Cambridge, and it's a hugelyvibrant atmosphere there. It was
a fantastic place to first beinvolved in biotech, and I
worked with Bruce Booth. He wasthe chairman of our board, and
(37:41):
again, another great mentor. Soagain, as I say, luckily,
through my career with peopleI've interacted with in that
way. The Oxford ecosystem offerssomething slightly different.
It's not as developed as theCambridge mass ecosystem, and
we're more spread out. We're notall in tech square. We're at a
science park, but there's anincredible amount of high
quality science in the UK andexcellent scientists, which
(38:03):
offer a great opportunity tothink about new approaches to
developing new drugs forpatients, whether that's for
Sitryx, specifically withinimmuno metabolism, or beyond
that, in my venture partner rolewith SV health investors. So I
really enjoyed becoming part ofthat UK ecosystem and starting
to think, how can I bring someof the experience that I have
(38:24):
from the US into the UK to helpus, you know, make more from
from the really good qualitysubstrate that we have.
John Simboli (38:32):
Thanks for speaking with me today, Iain.
Iain Kilty (38:34):
Thanks, John. I really enjoyed the conversation.
Today I'm speaking with Iain Kilty, CEO of Sitryx
(00:03):
therapeutics, headquartered inOxford, UK. Welcome to BioBoss,
Iain.
Iain Kilty (00:09):
Thanks, John. I'm looking forward to the
conversation.
John Simboli (00:12):
Iain, what led to your role as CEO at Sitryx?
Iain Kilty (00:15):
So I took on the role relatively recently,
actually just a couple of monthsago, but I've been working with
Sitryx for just over the lastthree years. I was the CSO
before transitioning into theCEO role, and it was a great
opportunity for me to lead acompany that I'm passionate
about and really believe that wehave a chance to have a huge
impact on patients who sufferfrom autoimmune diseases. And
(00:38):
that's really been the area I'vespent my whole career in
different guises. So prior toSitryx, I was working in
Cambridge Mass actually, withAtlas venture, as a CSO for one
of their immunology companies,but also as an entrepreneur in
residence, helping them seed newcompanies in that space. But
spent the bulk of my careeractually at Pfizer. I was at
(00:58):
Pfizer over 20 years, both USand UK, always in the immunology
space, but a variety of roles,from leading early target
discovery teams through toleading clinical clusters in
rheumatology and dermatology,before ultimately being
responsible for theirpreclinical portfolio in INI.
And as part of that role,actually, I was doing a lot of
(01:19):
work, working with biotech, andwhilst, I guess lots of
fantastic things about BigPharma and Pfizer and had an
amazing time there, learnt ahuge amount, had the opportunity
to contribute to marketedtherapies now, but the dynamism,
the opportunity to impactthings, to really drive programs
at speed and take risks was wasmore available to me in the
(01:43):
biotech world, and I've reallyenjoyed making that transition.
John Simboli (01:48):
What's it like to be a CSO and then become a CEO?
What sorts of understandings doyou have now? I know you're in
the job relatively a short time,but what's it like to be a CSO
versus what's like to be CEO?
Iain Kilty (02:01):
Yeah, so it's, as you say, relatively early in my
CEO experience, but the previousCEO actually is chap called Neil
Weir. He was the CEO from thestart of Sitryx, and when the
company was founded, and he'sstill within the company, he's
now president of the company.
Which is great for me, becauseNeil's been a mentor all the way
for me since I joined Sitryx,and this was part of a
(02:22):
succession planning it was evendiscussed as I very first joined
as the CSO. And obviously, as aCSO, you're primarily focused on
driving that scientificportfolio. And I joined at a
time the company was reallyevolving from having some early
targets to driving those targetstowards development candidates
and needing to become more of aprofessional drug discovery or
(02:43):
drug development organization,which was a huge amount of fun,
and we've now been able todeliver multiple programs
through those stage gates. Sowith respect to the transition
of role over this time, Neil'sgiven me opportunities to be
heavily involved in the investordiscussions, the pitches, the
strategic thinking of thecompany and so on. So it's less
(03:04):
of an abrupt you're thescientist. Oh, now I want you to
be involved in all of theseother things than a transition
over time, which has been greatbecause, obviously I know the
company very well. It's not likecoming in as a CEO and trying
and learning the science,learning the strategy and so on.
I've been involved in buildingthe company to this point, and
that was one of the reasons thiswas a really exciting
(03:26):
opportunity for me. Because Isaid earlier, I think I have
great belief that we have achance to really make a
difference for patients in whatwe're doing. I really like the
team, and I think we have somereally quite exciting assets to
take forward to the clinic now.
The key thing even in theseearly days, is my focus is
moving away from that managementof that scientific portfolio on
(03:48):
a day to day basis to all theother pieces, thinking about the
discussions with the bankers,the discussions with lawyers
working with the board, andthat's an interesting reporting
relationship that's new for me,I've always had a direct boss,
and whilst I report into thechair of the board, Pierre
Legault, and he's been also agreat mentor for me, you have
(04:09):
lots of other players on theboard as well who are from
different institutions,different organizations that
you're working with. So hugeamounts for me to learn on that
front, lots of connections, lotsof talking to people and a lso
important for me within theSitryx organization, that it's
not just the science part of theorganization that feels they
know Iain. Now we're smallenough for 45 people that I knew
(04:32):
everyone anyway, but it's adifferent relationship now to
make sure I'm interacting withthe finance team and in a
different way, the operationsteam and so on and so forth. So
yeah, lost lots to learn, butit's a transition more than any
sort of revolution in the wayI'm doing things
John Simboli (04:49):
From early on in your in your career, your 25
years with Pfizer, did youpicture at some point being a
CEO? Or is this something thatsort of evolves as time goes
along?
Iain Kilty (05:00):
Yeah, so when I was at Pfizer, I don't think I
necessarily pictured myself asbeing a CEO. I think actually,
as I developed in my career atPfizer, I would take on new
levels of responsibility andalways enjoy it, and once you
got comfortable with that, you'dlook at the next role and think,
well, I could have more impactin that next role. And then look
for those opportunities to buildout my toolkit, build out my
(05:21):
experiences to be in a positionto take on those next roles. And
as I mentioned earlier, actuallyI spent a bit of time in the
clinical phase of drug discoverywhile I was at Pfizer, which was
not my initial background. I wasPhD scientist, very much lab
based early on in my career, butreally research focused. But
(05:42):
that experience for those fewyears was hugely impactful in
how I then did my job leading aportfolio through to
development, candidate,nomination and early, early
development, So phase one, 1btype work. So in a similar guise
as I talked about, I wasinteracting quite a bit with
biotech companies when I was atPfizer, and that's what really
(06:02):
fired my interest, that adynamic place to work. I could
really try and influence things.
I felt I could bring experiencefrom big pharma into that
biotech setting and add value.
And to me, that's one of themost important things. Am I able
to add value here and reallyprogress towards making drugs?
Because fundamentally, that'swhat I want to do. I want to
make drugs that change people'slives. And there's no feeling
(06:24):
quite like being involved in aprogram that you get the first
clinical data and you see it'sworking, and you think I was
involved in that. That was anidea that we had on a PowerPoint
slide and so on. So that drovemy transition into a biotech and
CSO was the obvious area foreven my scientific background.
But in a similar guise, my firstCEO, I worked with a lady called
(06:44):
Sam Truex at Quench Bio, who's agood friend, and again, another
great mentor. I've been reallylucky with the people I've
interacted and worked withthrough the years. And there
were lots of elements of whatSam was doing that she gave me
the opportunity to learn about.
And I thought, well, there'sareas here that I think I could
really help too, because I bringa different style, I bring a
different way of thinking. Andeven then, I wouldn't say I was
(07:07):
100% sure that my next goal isto be CEO, but I certainly felt
there were areas where I thoughtI could bring value again as a
CEO with a slightly differentbackground. Sam's background was
more business development than acore science and so on. So
joining Sitryx was similar andcoming in as CSO, not
necessarily absolutely settingmy heart on CEO at all, but, but
(07:30):
it really felt like there was anopportunity here, given what
I've already described throughthe transition with Neil moving
into a role as president and soon for me to take that next
step. And I really do enjoy thebusiness side of biotech as well
as the scientific side. And Ithink it's you bringing those
(07:51):
two pieces together that giveyou the best opportunity to
deliver those new drugs forpatients. And another quick
comment, some of the exposurethat I've had on that business
side has also come through myentrepreneur in residence role
at Atlas, and I'm a venturepartner with SV health investors
right now in London, and thosethings, you start to see those
(08:12):
elements of the job. And again,felt, well, I think there's
value I can add. I've gotexperience pre clinically, and
clinically, the company's movingto more of a clinical phase now,
and it's the next step indevelopment for me, and
hopefully I will be able to addreal value to Sitryx.
John Simboli (08:30):
I want to ask you about the leap of faith part of
this. You were well prepared, asI've understood what you just
told me, and it's quite logicalin some ways, in most ways, to
follow that path that youfollow. On the other hand, there
is, I would say, probably, formost people I've spoken with,
there is a leap of faith aboutgoing from something that's very
big, like Pfizer or BMS orwherever it might be, to
(08:53):
something that's new and gettingstarted. And I remember a
conversation with two founderswho, one co founder spoke to the
other and said, I'm thinkingabout starting this company,
would you like to join me? Theother guy said yeah, and they
were both really excited as theytold me the story, and then they
said, then we went home and toldour wives. So that's the part of
the question I want to ask youabout when you come to grips
with that, this is exciting, butthis is an unknown. How does one
(09:16):
negotiate that?
Iain Kilty (09:17):
Well, you're absolutely right, and you've
been in the environment, in BigPharma, but you've been
reasonably successful. It'sreasonably comfortable. You're
well compensated, and you'vealso, you've got teams you
really like, generally, I didanyway, that's the hardest
piece, in many respects, wasleaving some of the people.
You're also leaving value on thetable, because you have various
options and all the rest of it.
So it is an element of leap offaith. It was interesting. I
(09:40):
didn't need to go back to mywife and sell this. She knew
that I was really ready to go,probably before I did, in some
respects, because she could seehow energized I was when I was
working with those biotechteams, through some of the work
I was doing for Pfizer at thetime, and how I'd come back and
talk about it and the receptionsI'd been. And chatting to those
guys, and I obviously discussed,I think I could, I could have an
(10:03):
impact, that I could, I could dosomething that's valuable. And
she, she was very encouraging,actually, well, if you believe
it, just go, you should do it,which was fantastic. It's
fantastic to have that sort ofsupport at home, because yeah
there's definitely anervousness, and it's really
interesting because one of thethings I was most nervous about,
actually, was job securitymoving into a small company. I
was the fourth employee atQuench Bio when I moved there,
(10:26):
so it was a small company at thetime. But I'm not sure that
actually, now I've been in thatworld for a number of years, I
don't think that's really theright thing to be concerned
about, because the reality isthat with any of these, with any
of these investor ecosystems, ifyou do a good job within that
ecosystem, there's always needfor people with experience and
drive to join other startupcompanies or establish biotechs.
(10:50):
There's no shortage of roles.
Now, your company name maychange more than it would at a
Pfizer and so on, but, but Ijust don't think actually
there's that there's such a bigdifference in job security. It's
just a different type ofsecurity, as long as you could
deliver. And I guess then theother piece that you always
have, and you have as you step,well, I have as you step, from a
CSO into a CEO role, is there'salways an element of, you know,
(11:14):
can I, can I do thiseffectively? You know, there's
always a bit of impostersyndrome. And mind you, those
sort of things, you know thatthose things keep you sharp,
keep you focused, make you workhard, so I think that's just all
part of the process.
John Simboli (11:27):
So here's a related question about how
people think of a CEO ascompared to another C suite job.
So I spoke with a person who wasthe Chief Business Officer at a
biopharma company. And he toldme that he was accustomed to
going into the meetings with CEOand the other members of the
(11:47):
team and posing options, youknow, we could do this. We could
do this. And then he said, whenhe became CEO, he just without
even understanding that he washe was doing that, he was
explaining to his team we coulddo this and this. And he said
frequently, suddenly they wouldturn to him and surprise, he was
surprised by this, and turn tohim and say, yeah, but which one
(12:07):
are we going to do? So there isa collaborative aspect, but
there's also an expectation,right, that the CEO will be a
final decider. So again,probably early in the cycle,
maybe I should ask you this insix months, but do people look
at you any differently as theCEO than they did as the CSO
internally?
Iain Kilty (12:26):
I think so. I mean, my natural style is I do like to
make decisions. And we've donevarious analyzes with our LT,
you know, all the differentHogan type analyzes and things
to look at our different stylesand I'm probably the strongest
decision maker style within theteam. So that piece is quite
natural for me, and I quiteenjoy that, being able to make a
(12:48):
decision and move on. I like tomake a decision before we leave
the room. But yeah, obviously Ilike to listen to the team and
so on. Now, as a relativelyearly stage biotech just moving
our first wholly owned programto the clinic now, a lot of what
we're talking about is in myarea of expertise, because it's
the drug discovery piece. So Ifeel comfortable around that
(13:08):
drug discovery development. Itgets a bit more tricky if you're
talking about decisions you needto make around a legal decision
or a decision about some thingswe've been talking about
recently, the lease and labspace we might want versus not,
and some of those things. Soyes. So I think as you move more
out of your comfort zone, thosesort of decisions get harder,
(13:29):
don't they? Now what's great isI have a really good leadership
team who I can rely on to adviseme and to be involved in that
debate around any of those sortsof decisions that need to be
made. But yeah, no doubtthere'll be challenges in the
future in that way. I thinkactually, one of the things I've
(13:49):
already seen is just peopletreat you differently once
you're the CEO, because you'renot quite a peer anymore. And
some of those, you know, much ofthe team, it's many of the team
were my peers previously. Andwhilst you don't, I don't
personally feel any different.
You do notice the style ofpeople's interaction can be
subtly different. And I thinkyou just have to get used to
that, that you know you're in aslightly different position.
John Simboli (14:11):
When you first came to Sitryx, do you recall
what it was in particular aboutthe science that grabbed hold
you? I'm sure you looked athundreds of other options and
possibilities at that timecoming from Atlas, you saw many
different things, I'm certain.
So my question is, do you recallwhat it was specifically about
Sitryx that made you say, Ireally want to investigate this?
Iain Kilty (14:31):
Yeah so there's, there's a few elements to it,
actually. So I had theprivilege, again, working at
Pfizer, to work on particularlyjak kinase inhibitors, which
have become drugs and otherprograms which have really had
an impact on patients, which isgreat. The way that those
approaches work is that they'resuppressing elements of the
(14:52):
immune system, and from thereyou can drive a certain level of
disease remission, but we kindof got stuck with the amount of
disease remission we can achievein rheumatoid arthritis, in
inflammatory bowel disease andother indications. So we need to
start thinking slightlydifferently about how can we
really move that needle to drivegreater therapeutic benefit for
(15:13):
patients and drive morepatients, as I say, into true
remission and sustainedremission at that. So actually,
when I was at Pfizer, we werelooking at different areas we
could invest in to do that. Andone of the areas we felt really
had that potential wasimmunometabolism. So we actually
had a group there, when I was atPfizer, focused in this space.
(15:34):
It was a space I knew prettywell. And the fundamental thesis
for immunometabolism is that bymodulating the metabolic pathway
cells are depending upon, youcan modulate the phenotype of
those cells. So you can move acell from in effect, a pro
inflammatory cell, to more of aregulatory or homeostatic sort
of type cell, and that has thepotential to really drive much
(15:57):
greater efficacy for patients.
So the disease area wasinteresting to me. I think the
other elements were, it's asmall molecule company. I've got
a lot of experience in thatspace. And going back to the
point I made about, do I think Ican make a difference in that
organization and really addbenefit? And then,
fundamentally, it's superimportant it's the right team.
(16:17):
And when I met previous CEO,Neil, Neil Weir, and some of the
other leadership team at thetime, I really felt that this is
a team that would be fun to workwith, but know what they're
doing and have a clear vision ofwhere they want to go. And
equally, we have a greatinvestor base, and that's also
incredibly important, as youknow, in the biotech world,
(16:37):
seasoned investors who reallyunderstand drug discovery and
development and I had theopportunity to meet with a
number of the investors as wellbefore I took the role and and
again, was really encouragedthat they would be great people
to work with. So it was amixture of the science made
sense to me, I already knew someelements of it, the team were
great and the investor base wasgood.
John Simboli (17:02):
When you tell someone who's from outside the
industry that you're the CEO ofSitryx therapeutics, what do you
think they picture you doing allday, and what do you do all day
when you try to explain to them,no, I do this.
Iain Kilty (17:15):
So usually, if I'm asked, what do I do for a
living? I would say, well, Iwork in a company where we're
trying to make new drugs to helppeople with autoimmune diseases,
diseases like arthritis andinflammatory bowel disease,
eczema and so on. And thenpeople have usually got a
reference point there that theyknow somebody who who struggles
with one of those diseases. Andthen perhaps, if that piece is
(17:37):
clear, and they say, oh no, Iunderstand that. But, is it
pharma biotech, then I wouldjump in and say, well, I built a
lot of my experience and skillset working in Big Pharma, but
now I work in biotech and enjoyworking there because of the
dynamic nature of that business.
But it's an ecosystem. Bigbiotech needs Big Pharma. Big
Pharma needs biotech, so westill work closely with pharma
(17:59):
and spends a lot of time withthose teams. And then to what do
I specifically do there? Well,I'm a scientist at heart. I'm
focused on developing drugsthat'll change people's lives,
and perhaps tell them a bitabout our lead programs in
eczema. A lot of people knoweczema, and so you know this,
this, it's a small molecule,it'll be it's a pill. If it
(18:21):
works people, it'll really helpthose people with more severe
disease. So, so trying to findthose reference points that make
sense to people.
John Simboli (18:30):
Can you recall when you were eight or nine or
10 or some formative stage andyou were thinking, my parents,
this is as a kid, of course, myparents think I should become a
kind of connected to, gee, I'minterested in this. Does any of
that have anything to do withhow your professional life
played out?
Iain Kilty (18:46):
It certainly does, to a degree. I think my parents
and probably even I as a child,always knew I'd be involved in
the sciences somewhere. I was asort of kid who asked the why
question all the time. I wantedto take things apart, understand
how they worked. I used to loveall the sciences, actually, so I
didn't know which path I wouldfollow. Would it be physics,
chemistry, biology? It alwaysfelt like it was going to be
(19:10):
something in one of the in oneof those directions, because
that was what fired me up as achild, reading about nature,
being out in nature. I grew upin Cumbria in the northwest of
the UK, and it's a stunningarea. It's right by the net Lake
District National Park. So usedto spend lots of time out in the
Fells and so on there and thatused to really inspire me, that
the again, just being in natureand trying to understand it,
(19:33):
geography also. So did I knowI'd be in a biotech company? I
probably wouldn't have knownwhat a biotech company was at
that time. But did I think I'dbe doing something scientific?
Probably, that's probably what Iwould have told you. I want to
be a scientist or a doctor orsomething that has a link to
science. But yeah.
John Simboli (19:54):
Do you recall at a later stage, when you were in at
university or in medicaltraining, whatever's the
appropriate part for thisquestion, can you remember,
yeah, that's exactly the part ofit that I want to investigate.
Maybe, as a professor, maybe itwas an idea that, yeah.
Iain Kilty (20:11):
Yeah, so I actually, I did my first degree in
Cambridge in the UK. And thescientific degree you enter
Cambridge in is called naturalsciences. So it starts quite
broad, and I actually enteredthinking I'd be a chemist. So my
first year, I was thirdchemistry, third molecular work,
(20:31):
molecular biology, and then athird sort of zoology type work.
But it was really with a view tochemistry and moving forward.
But actually, once I got there,I got really inspired at an
electrical Bruce Ponder, he wasone of the guys who identified
the BRCA gene mutation in breastcancer. And I remember he, I
still remember when he gave atalk about this, and I thought,
(20:53):
this is amazing. This isactually the world I want to go
into at that point, because thisis changing people's lives. He's
worked out one of the causes of,you know, familial breast
cancer. So it was fascinating.
And really it was the influenceof people like him that that
moved me from the chemistryfocused more towards a molecular
biology and biochemistry. And aspart of that, I did pharmacology
(21:15):
work and so on. I think theother thing that made me think
is, I'm probably not a long termacademic. I really want to think
more about the applied nature ofthis medical research or
scientific research, and then itjust, it really just evolved
from there, went on to a PhD andthen into an industrial postdoc
(21:37):
after that.
John Simboli (21:42):
If someone says, who is Sitryx therapeutics, how
do you like to answer that?
Iain Kilty (21:45):
Yes, Sitryx therapeutics are an immunology
focused company, but withinimmunology, we're exploiting
immunometabolism to drive agreater anti inflammatory
response in chronic, autoimmuneand auto inflammatory diseases.
The real potential here is thisfundamental thesis around
immunometabolism, that bymodulating metabolic pathways,
(22:07):
we can reset the phenotype ofinflammatory cells, so we're not
blocking a single pathway or asingle cytokine. We're moving
the cell to more of a noninflammatory cell type, so
that's not immunosuppressive. Sothat's quite different to
current anti inflammatorytherapies, and we think offers
that potential to drive muchgreater efficacy for patients.
(22:29):
It's a company that was foundedby a number of the leaders in
the immuno metabolism space. Oneof our founders, Luke O'Neill,
has really driven a lot of theliterature. Jeff Rathmell, Mike
Rosenblum, Jonathan Powell, allgreat scientists working in the
field, and that's given us agreat basis in scientific
knowledge. And then what we'vedone is combine that with a team
who've got both big pharma andbiotech experience, certainly
(22:52):
within the leadership team, sothey know what good looks like,
but they can also work nimbly tothen be able to exploit that
science and deliver noveltherapies to the clinic.
John Simboli (23:02):
Is there a way to talk about the mechanism of
action for the lead candidatefor the eczema candidate that
you'd like to talk about?
Iain Kilty (23:10):
Yeah, so our LEAD program is a PKM2 activator
program. So PKM2 is an enzymethat's involved in glycolysis.
It's been a well characterizedenzyme for a number of years,
but about a decade or so ago, itwas shown that as well as this
role in glycolysis, this enzymehas a moonlighting role
regulating gene transcriptionwithin the nucleus of cells. And
(23:33):
the way it regulates whetherit's driving glycolysis or
driving gene transcription iswhether it exists as a dimer or
a tetramer, so it says anequilibrium between the two in
cells, and the dimer will drivethe nuclear pro inflammatory
gene transcription. The tetramerwill drive glycolysis. So our
small molecules induce formationof that tetramer, so skew you
(23:55):
away from that nuclear activityand maintain that metabolic
activity. And the net effect ofthat is you could, you reduce,
particularly lymphocyte T and B,lymphocyte proliferation,
cytokine production and antibodyproduction.
John Simboli (24:11):
How do you see the lead candidate in terms of your
vision for the portfolio as awhole? Where does it fit in?
Iain Kilty (24:19):
So our lead candidate has helped us really
build our understanding of howto prosecute immunometabolic
targets. And one of the things Ihaven't really touched on yet,
but is absolutely critical inprosecuting this target class,
is looking at cells in theappropriate cellular context.
And what I mean by that is, ifyou're growing cells in media
with lots of glucose, aminoacids, oxygen and so on, that's
(24:43):
designed to keep cells alive.
That's nothing like aninflammatory site where the
cells are competing with eachother for all of those things,
amino acids, glucose, and it'soften hypoxic and so on. So if
you really want to reveal thepharmacology of modulating
metabolic pathways, you need tomodulate the environment the
cell is in and build confidencethat's relevant to the
(25:04):
inflammatory state in disease tounderstand the pharmacology. Now
our lead program is a greatexample of that where the
pharmacology is only revealedunder conditions where the cells
have depleted extracellularserines, the amino acid serine,
and then what happens is cellsneed to make their own serine.
Under those conditions, they upregulate this serine
(25:24):
biosynthesis pathway. That'swhen you see the pharmacology of
PKM2 activators in T lymphocytesand B lymphocytes. So there's a
lot of reasons that's exciting,because that means you've got a
very laser targeted approach toit sites where serine is being
used up, not just in the blood,where you'll have high levels of
serine, but at thoseinflammatory sites where you're
getting competition. But it alsoprovides, if you'd like, an
(25:48):
initial way to think about anynew target that we bring in. So
not every target is going to bedependent on serine. Other
targets are going to bedependent on other mediators,
and they may be relevant todifferent situations. So those
sort of insights have beenimportant in how we've then
prosecuted the future portfoliobeyond PKM2. But I say we're
very excited about PKM2. There'sclear medical need in eczema,
(26:12):
and a small molecule, once ortwice a day pill that could
really drive efficacy for thosepatients in a safe manner would
be hugely beneficial.
John Simboli (26:23):
Sometimes, when I talk with folks on BioBoss, I
find the discussion is largelyaround the scientific puzzle,
how do I unravel this? How do Imake sense of this? How does our
company move this forward? Andthen other times, the discussion
will also include, if this worksthe way I think it will I can't
wait, because I can see how thiscould have an effect on
(26:44):
patients. And of course, the twoare intertwined. You couldn't do
one without the other. Butthere's like a shifting thing
that happens over time in myexperience. So where are you on
that process? Are you, are youfocused primarily on
understanding how this all maywork. Do you also allow yourself
to think about, jeez if thisworks this is going to really do
(27:05):
some good for some people.
Iain Kilty (27:07):
Yeah, absolutely allow myself to think the
latter. I think that's the thingthat makes you jump out of bed
in the morning. So if I didn'tbelieve it had that potential, I
wouldn't be as excited about it.
I think the potential here isthat we can really drive a shift
in immune cell phenotype fromdriving inflammation to more of
a homeostatic or noninflammatory regulatory
(27:29):
phenotype, and that has thepotential to drive sustained
remission for patients whichwhich would be huge. Our lead
program is focused on eczema,although we do think this asset
could have value acrossadditional indications, and
there's clear medical need therethat there's a real breakthrough
a number of years ago whendupilumab dupixent was approved.
It's a biologic that modulatesL413. But that that drug, about
(27:51):
50% of the patients get a 75%improvement. So that's similar
to an anti TNF in psoriasis. Sosignificant, makes a huge
difference to patients, butthere's a lot of medical need
remaining, and the next wave ofcompounds were Jak inhibitors. I
worked on some of those when Iwas at Pfizer. One of those is
now an approved drug, which isgreat, and they do give slightly
more efficacy because theyintegrate more pathways than
(28:13):
that 413 pathway But there aresome limitations around the
label and the safety of thoseassets. So if we could achieve
efficacy similar or better, butwith a much safer therapy, that
for patients would be have ahuge impact, and that's what
makes me jump out of bed in themorning. I think we have some
really nice data to say thatthat may well happen, but we've
(28:33):
got to generate the clinicaldata to say, is that true? But I
truly think that that isexciting.
John Simboli (28:40):
Do you see that as a potentially incremental change
for patients? As somethinggreater than that? It's going to
vary from patient to patient,but.
Iain Kilty (28:49):
I think it has the potential to be greater than
that. I think it will vary frompatient to patient, which is
nearly always the case. Alwaysgets some really good responders
and some people who are notresponding as well to the
therapy. But just because ofheterogeneity within the
disease, but also, there's ahuge element of convenience here
for patients to be able to takea pill on a day to day basis, as
(29:10):
opposed to a two weeklyinjection. I think for a lot of
patients it'll increase accessas well. More patients will
actually be able to get hold ofthat drug, I would hope, and
therefore get that benefit.
John Simboli (29:21):
When you tell the story about Sitryx and people
get it wrong, do you ever see apattern about why they're
getting it wrong, even thoughyou said it a different way,
they heard it a different way,and then you can help them to
get back on track. Another wayof saying this, how might people
misperceive what Sitryx isabout?
Iain Kilty (29:39):
Yeah. So I think the biggest misperception we see is
actually more on the safety sideof things, if you're interfering
with metabolism. So gettingpeople comfortable that we're
not interfering with fundamentalelectron transport, chain type
metabolism. What we're focusingon are those metabolic changes
(29:59):
we're seeing at inflammatorysites, those cysts, those
pathways which upregulated tomake a TH17 cell more active or
or a macrophage produce morecytokines and so on, and to
really helping people tounderstand that by targeting
specific enzymes whichupregulated at those sites, but
also the importance of cellularcontext that we talked about
(30:22):
earlier will drive a veryfocused pharmacological effect.
So it's not a broad effect thatyou'll see across all tissues,
and that tends to be a placewhere people can, yeah, they
come in, possibly with a biasthat I can't see how you could
do this in a safe manner. Now,the nice thing we can do now is
(30:42):
that we have a program that Lilyopted into at IND last year. So
we show that we can generategood margins through GLP talks,
which gives you some confidencethat this isn't a type of
approach which can never besafe. And now our lead program
is at a similar stage withinSitryx, our wholly owned
program, as well, where, again,we've shown good margins through
(31:04):
GLP talk studies. Which so Ithink as we build that data set,
people will get more comfortablewith that. But conceptually,
that can be a challenge earlyon.
John Simboli (31:12):
For the people who like the devil's advocate
approach, sometimes the questionfor the CEO becomes, well,
that's a great idea, but if it'ssuch a great idea, how come
nobody else did it? So I'm sureyou get variations on that from
time to time. What's the bestanswer for that?
Iain Kilty (31:27):
Well, I think the science is evolving all of the
time, and people actually havefocused on immuno metabolism in
cancer in the past, whichactually has been a good source
of targets and certainly toolcompounds for us to validate
mechanisms and pathways, and ithasn't necessarily been the most
efficacious therapy in cancer,but you're trying to do
something very different incancer. In cancer, you're trying
to block a pathway to kill acell. What we're doing is
(31:49):
blocking a pathway to driverewiring of the pathway to
different metabolic pathwayswithin the cell and changing the
phenotype of the cell. Andthat's actually what was seen in
some of some of the oncologystudies. So we've learned from
the oncology studies, and thenapplied that to immunology. So I
think it's actually reflectiveof the evolving science, and
that we're part of the firstwave there. And then I'd go back
(32:11):
to again, that we just havegreat founders who are a number
of the leaders in the field thathave helped us move at speed.
And we continue to work reallyclosely with particularly Luke
O'Neill and Mike Rosenblum forcompletely different things,
actually, but work closely withthose guys as we drive forward
our portfolio.
John Simboli (32:29):
Who makes a good partner to Sitryx therapeutics?
Iain Kilty (32:32):
We're really lucky, actually. We have some fantastic
partners at different levels. Sogoing to some of our founders,
academic partners, I'vementioned Professor Luke O'Neill
a couple of times from TrinityCollege, we have a postdoc in
his lab, but we have joint labmeetings with with Luke, and a
really open dialog. And I thinkthat really helps us, because
that keeps us at the cuttingedge of the academic science in
(32:52):
this space, and also helps, fromhis side, he learns more about
the pharmacology, and we'regetting great tools, which he
can then use in his science. Sothere's joint benefit there. But
the other really goodpartnership we have is with Eli
Lilly. So we signed that deal,actually just before I joined
Sitryx, and they've worked withus on a number of programs. They
(33:13):
opted into one of our programslast year that was IMD, which
they now fully run, and it's inphase one development. And we
have a second program we'reworking on with those guys. And
the way that works so well,actually, is that we just,
again, we have joint projectteams. It's really open between
the two companies, and we bringdifferent skills to the table.
So we own the strategy atSitryx, but it's hugely helpful
(33:37):
to be able to pull on theknowledge of the Lilly team and
ensure that we're fully alignedas we're moving things forward.
The last thing we want to do isprovide a package that doesn't
align with their needs. Andthey're very good as well.
They're not, certainly notobliged to, but they do help
generate various data fromdatabases they can access that
we can't, that help us moveforward more efficiently. So I
think the similarity in bothcases is that openness. I'm
(33:59):
really trying to work as oneteam with a common goal. The
science has to be good. If ascience isn't good, then doesn't
matter if you put the best teamin the world in it, you won't
deliver drugs. But you can havegreat science with a team that's
not functional, and you're notgoing to get there either. And I
think the culture that's beenbuilt at Sitryx has really
enabled the company to moverapidly to the point we are
(34:20):
today, and it's just a fun placeto work for those reasons. And I
think, as well, has facilitatedthis close collaboration, with a
couple of examples I was givingyou earlier, around the academic
collaborations and theindustrial collaborations.
John Simboli (34:34):
If I were to ask people on your immediate team,
you know, what's Iain'smanagement approach, how do you
think they would answer there?
Iain Kilty (34:41):
Yeah so, I think they would answer that I'm
approachable and very calm. I'vealways been told I'm a very calm
person, which is great. Like tolisten to everybody's views, but
I really do like to have adecision made. It doesn't always
have to be my decision. I justdon't like leaving a room
without a clear plan. And Ithink they would probably
reflect that ss well in theirfeedback. And I'd certainly
(35:03):
hope, as I said, that they wouldfeel that I'm accessible and
they can chat to me. And there'scertainly elements of evidence
for that that I take comfortfrom, that that's true. You get
bits of feedback, but as we wentthrough the transition, a number
of those quite junior teammembers would come and chat to
me about, oh, if in this newrole, will I still have chance
to ask you about this, and can Ishare these thoughts or whatever
(35:23):
it might be? And I was reallypleased that people were willing
to come and take some time withme to talk about any concerns
they had about any changeswithin the company.
John Simboli (35:33):
How do you know when it's time to make a
decision versus when it's timeto look for more information?
Iain Kilty (35:39):
Yeah, it's a great question, especially in
research, because I don't thinkyou ever really know, are you at
60% of the information? Have Igot 90 or actually 20? How far
do I need to go? So a lot ofthis, I think, comes from some
experience, and also just theimportance of the decision and
the impact of the decision. Soif this is a relatively small
(36:00):
decision, it's $5,000 to bespent on study x, or whatever it
might be, then I think you canbe pretty comfortable making
those decisions with relativelysmall amounts of information. If
the decision really could impactthe future of the company and
the direction you're going togo, and maybe something you
couldn't easily undo, then youreally need to make sure you've
(36:21):
done as much diligence as youcan. But I do think one of the
things from my experience inboth big pharma and biotech,
that if you get into a placewhere you can't make a decision,
then you're in trouble, becauseyou've almost made a decision by
not making it, you're juststatic, and if you're not moving
forward, you're movingbackwards. So I think you've
obviously got to be careful.
You're not ready fire aim. Youneed to give yourself chance to
(36:45):
have really thought thingsthrough and had the appropriate
diligence around a decision thatyou make. But it can be
comfortable sometimes,especially for the more
difficult decisions to say,okay, let's get back together in
two more weeks, and we'll doresearch X and come back to this
decision. So I just think, youknow, you have to be careful,
because you've, you've actuallymade a default decision there.
John Simboli (37:06):
Is anything about the origin story and the
community that is there inOxford and in UK in general,
that would be interesting foryou, in your opinion, to talk
about?
Iain Kilty (37:19):
Well actually I was in Cambridge, Mass for 10 years
before I took this job, so thatwas quite a different
environment. So first I cancomment on that. So I originally
was in biotech, working withAtlas venture in tech square in
Cambridge, and it's a hugelyvibrant atmosphere there. It was
a fantastic place to first beinvolved in biotech, and I
worked with Bruce Booth. He wasthe chairman of our board, and
(37:41):
again, another great mentor. Soagain, as I say, luckily,
through my career with peopleI've interacted with in that
way. The Oxford ecosystem offerssomething slightly different.
It's not as developed as theCambridge mass ecosystem, and
we're more spread out. We're notall in tech square. We're at a
science park, but there's anincredible amount of high
quality science in the UK andexcellent scientists, which
(38:03):
offer a great opportunity tothink about new approaches to
developing new drugs forpatients, whether that's for
Sitryx, specifically withinimmuno metabolism, or beyond
that, in my venture partner rolewith SV health investors. So I
really enjoyed becoming part ofthat UK ecosystem and starting
to think, how can I bring someof the experience that I have
(38:24):
from the US into the UK to helpus, you know, make more from
from the really good qualitysubstrate that we have.
John Simboli (38:32):
Thanks for speaking with me today, Iain.
Iain Kilty (38:34):
Thanks, John. I really enjoyed the conversation.
Popular Podcasts
On Purpose with Jay Shetty
I’m Jay Shetty host of On Purpose the worlds #1 Mental Health podcast and I’m so grateful you found us. I started this podcast 5 years ago to invite you into conversations and workshops that are designed to help make you happier, healthier and more healed. I believe that when you (yes you) feel seen, heard and understood you’re able to deal with relationship struggles, work challenges and life’s ups and downs with more ease and grace. I interview experts, celebrities, thought leaders and athletes so that we can grow our mindset, build better habits and uncover a side of them we’ve never seen before. New episodes every Monday and Friday. Your support means the world to me and I don’t take it for granted — click the follow button and leave a review to help us spread the love with On Purpose. I can’t wait for you to listen to your first or 500th episode!
Crime Junkie
Does hearing about a true crime case always leave you scouring the internet for the truth behind the story? Dive into your next mystery with Crime Junkie. Every Monday, join your host Ashley Flowers as she unravels all the details of infamous and underreported true crime cases with her best friend Brit Prawat. From cold cases to missing persons and heroes in our community who seek justice, Crime Junkie is your destination for theories and stories you won’t hear anywhere else. Whether you're a seasoned true crime enthusiast or new to the genre, you'll find yourself on the edge of your seat awaiting a new episode every Monday. If you can never get enough true crime... Congratulations, you’ve found your people. Follow to join a community of Crime Junkies! Crime Junkie is presented by audiochuck Media Company.
Ridiculous History
History is beautiful, brutal and, often, ridiculous. Join Ben Bowlin and Noel Brown as they dive into some of the weirdest stories from across the span of human civilization in Ridiculous History, a podcast by iHeartRadio.