Latest / The BioHub - by Avetix / Episode 179 - Tosh Butt - CEO of Navigator Medicines

Transcript

Episode 179 - Tosh Butt - CEO of Navigator Medicines · The BioHub - by Avetix

• 0:06
  So Tosh, welcome to the podcast. Great to have you on.
• 0:09
  Hi Callum, pleasure to be here. Looking forward to our
• 0:11
  conversation. Nice.
• 0:13
  I I think we're going to get into the Navigator Medicines
• 0:16
  story in in a little bit, but I think it's always nice to start
• 0:20
  off with a little bit of your background and about your story,
• 0:24
  right. I want to take it back to when
• 0:26
  you were sort of even at uni Tosh going going a little way
• 0:29
  back there, like what drew you into to buy a pharma initially
• 0:34
  or healthcare more broadly, I guess?
• 0:37
  Yeah, well, I'll take back to university today.
• 0:39
  My goodness, Callum, I'm going to have to clear out some
• 0:41
  cobwebs here, you know, But yeah, so I'm a pharmacist by
• 0:45
  training, and I chose pharmacy because I love science, find it
• 0:51
  really fascinating, and it really gets my curiosity going.
• 0:57
  And so I thought that would be a great field to get a career in,
• 1:02
  but I wanted to do something a little bit more practical than
• 1:05
  straight up bench science. Not, not that there's anything
• 1:08
  wrong with that didn't really excite me.
• 1:11
  And so I wanted to do something practical with science.
• 1:13
  So I thought pharmacy might may allow me to do that, but I still
• 1:16
  didn't have ambitions to be a pharmacist.
• 1:18
  So once I graduated, I qualified as a pharmacist, spent some time
• 1:22
  working in retail in Boots, the chemist.
• 1:25
  But before I decided what I really wanted to do, and I
• 1:27
  thought to myself, you know what?
• 1:28
  The farmer industry could be a nice combination of where my
• 1:33
  interests lie, where my experience lies and where my
• 1:36
  skills lie. And that's how I decided to
• 1:39
  choose upon the farmer industry. And I got into the farmer.
• 1:44
  I got into Glaxo, which is my first job, purely by chance.
• 1:47
  I was at a job fair in Kensington Olympia in central
• 1:52
  London or just West of central London, walking around a big,
• 1:56
  big exhibition hall and somebody from GSK at the time asked me to
• 2:02
  come over and say had I considered a career at Glaxo?
• 2:06
  I had to some extent. I knew you Glaxo were, but I
• 2:10
  hadn't really done any specific research about Glaxo.
• 2:13
  So anyway, I that's from that conversation spurred a whole
• 2:17
  bunch of interviews, etcetera, etcetera, a job offer and the
• 2:20
  rest is history. A small anecdote there.
• 2:22
  The person who who called me and asked me to come to the Glaxo
• 2:26
  stand was a former Chief Commercial officer of Vertex, a
• 2:30
  guy called Stuart Arbuckle. I know Stuart, he he knows me,
• 2:35
  but I don't think he will. He will remember that chance
• 2:39
  encounter in Kensington Olympia in London and pulling me out of
• 2:42
  the crowd and asking me to listen to his sales pitch for
• 2:45
  Glaxo. But Stuart, it worked.
• 2:47
  Thank you for my career 25 years later.
• 2:50
  Definitely. I like, imagine telling those
• 2:53
  two people then and there that that's where they'd end up as
• 2:56
  well. That, yeah, probably wouldn't
• 2:57
  have been believed by either of you, I guess, at the time.
• 3:00
  So. That's right.
• 3:02
  That's right. And so look, Callum, yes, so
• 3:04
  look, I mean, in terms of my career, a quick landscape that's
• 3:07
  that's the quick landscape would be UK trained pharmacist.
• 3:11
  And then I worked at Black. So that I've just described
• 3:15
  primarily in sales, marketing, commercial roles, both
• 3:19
  operationally as well as above market.
• 3:22
  And then global, I was at Glaxo, then I went to Sanofi.
• 3:27
  I then went back to Glaxo and then I joined AstraZeneca.
• 3:31
  So the first, I'd say 6070% of my career would have been in
• 3:36
  traditional big pharma with those three companies, GSK,
• 3:40
  Sanofi and AstraZeneca. Thoroughly enjoyed it, met some
• 3:43
  amazing people, learnt some amazing things from many
• 3:47
  accomplished leaders and really, really good human beings.
• 3:51
  Thoroughly enjoyed that. And then several years ago I
• 3:55
  decided to make the leap over to biotech and I joined a Bay Area
• 4:00
  biotech called Chemocentrix in the immunology space.
• 4:04
  I've really enjoyed that. I then went to my second
• 4:06
  biotech, a Swiss biotech called Idorsia.
• 4:10
  And then I decided I really wanted to go to a start up
• 4:14
  biotech, go in when it's really, really at it's embryonic stage
• 4:19
  and it's and have that experience around company
• 4:22
  creation. And that's where I am now a
• 4:24
  navigator. And then in terms of geography,
• 4:27
  I've been very blessed. I had the pleasure and privilege
• 4:30
  of working in the UK, working in France, working in Latin America
• 4:34
  and then I've been in the US now for the last 20 plus years.
• 4:38
  Yeah, nice, nice. And I think going back to what
• 4:41
  drove you into the biotech side of things, it was the
• 4:45
  involvement with Fazenra AstraZeneca, right, where you
• 4:48
  had to sort of build out that team from scratch that really
• 4:51
  started to get the juices flowing, so to speak.
• 4:55
  That's right. Look, I look like I said
• 4:57
  earlier, kind of, I was really enjoying my time in big pharma.
• 5:02
  Like I'm working with some incredibly talented people,
• 5:04
  incredibly good people, good coaches, good trainers.
• 5:09
  And then in 2017, I was asked to set up our bendrolizumab brand
• 5:16
  name Fasenra for years in a philic asthma team at the time
• 5:21
  AstraZeneca, certainly the Wilmington office where we were,
• 5:24
  I was based was a, I'll call it a primary care shop for want of
• 5:29
  a better term. So this was going to be our
• 5:31
  first foray into the world of biologics and specialty
• 5:34
  medicine. Specialty distributors buy and
• 5:38
  Bill are working with a hub, all things that were alien to a
• 5:43
  primary care company. And so I was employee number one
• 5:47
  in that business unit. And over the course of just
• 5:50
  under 18 months myself with the team that I was, I was able to
• 5:55
  attract and hire. We got it to a just over 300
• 5:58
  people, just over 300 strong. Within 18 months, we launched a
• 6:03
  drug. It was tremendously successful.
• 6:05
  And when it's still one of my fondest experiences in the
• 6:09
  industry. And I asked myself, why do I,
• 6:11
  why do I say that? Why did I feel that then and why
• 6:15
  do I still feel that way today? What I really enjoyed was having
• 6:20
  a blank sheet of paper, being employee number one in a team
• 6:24
  and having everything there open to shape, which is a pretty
• 6:29
  unique position in big pharma. Because typically in big pharma
• 6:33
  when you're launching a new drug, you will be hiring people
• 6:37
  and talented individuals from across the organization because
• 6:40
  you have the resources there. But the brief I was given was
• 6:43
  that at least 90% of the people I hire of that 300 person team,
• 6:48
  it's going to have to be external because I'm going to
• 6:51
  have to be bringing in people who understand biologics,
• 6:54
  specialty medicine and all the capabilities and infrastructure
• 6:58
  and company wiring, the needs to set a company up for success to
• 7:02
  launch a drug like that and bring it to patients.
• 7:05
  So I really enjoyed that part of hiring people, creating a
• 7:10
  culture, working with the leadership team.
• 7:12
  And I thought to myself there was still something missing and
• 7:17
  I realised what it was, which is as much as I enjoyed that
• 7:21
  experience of launching Ffandra at AstraZeneca, I met some
• 7:25
  amazing people there, I really did.
• 7:27
  I learnt so much from them. When you do, what I realised is
• 7:31
  when you do it in a large company, you're still doing it
• 7:33
  with a safety net. And what do I mean by that?
• 7:36
  Imagine doing a trapeze act at A at a circus and you're doing it,
• 7:41
  but there's a big safety net underneath.
• 7:42
  So if you make a mistake or somebody drops you, there's a
• 7:46
  nice cushion. And Big Pharma has that to a
• 7:48
  greater or lesser extent because if things don't go well,
• 7:51
  essentially you get assigned to another business unit and you're
• 7:54
  working on another product or another therapy area and you're
• 7:57
  off to the races. And that's great.
• 8:00
  So maybe I'm a sucker for punishment.
• 8:02
  Maybe I'm a thrill seeker, maybe I'm a masochist.
• 8:04
  I don't know. You'd have to ask my wife and
• 8:06
  kids what adjective best describes me.
• 8:08
  But I thought I'd love to do that for Senra again, but
• 8:12
  without a safety net. I think that would give me a
• 8:15
  bigger sense of excitement, thrill, motivation, look to
• 8:19
  something, to something. I guess it would be scary.
• 8:22
  And those people don't join biotech.
• 8:24
  But for me, I wanted more of that.
• 8:26
  And that really, really opened the door for me to learn more
• 8:30
  about biotech, and I've loved it ever since.
• 8:33
  Yeah, I guess in early stage like, yeah, the trial is the
• 8:37
  company, whereas in big pharma the trial's a project, right.
• 8:41
  I guess in in some ways. So yeah, nice.
• 8:44
  I guess that leads us to navigate it because that's the
• 8:46
  first all taste of yeah, really joining at a super early stage,
• 8:52
  No safety net, really. Walk us through the origin
• 8:55
  story, Tosh, because it's it's quite an interesting 1, isn't
• 8:58
  it? Yeah, thank you, Karen.
• 9:00
  Yeah. So look, I, I will say, look, I
• 9:02
  mean, this is my third biotech, but I'm the first time CEO.
• 9:06
  So that brings with it an an extra set of opportunities,
• 9:11
  challenges, excitement, anxiety, all of the above when you're in
• 9:14
  a new position. But I'm absolutely loving that I
• 9:17
  work with an incredible team. But yeah, how the company was
• 9:21
  formed, you know, I'll talk about how the company was formed
• 9:23
  and then I'll talk about a little bit about navigate to how
• 9:26
  the company was formed. We were formed in August of 2024
• 9:31
  and we were formed from an incubator company called Sierra
• 9:37
  Medicines. Sierra Medicines is an incubator
• 9:40
  that's in a large part owned by RA Capital, who are a well
• 9:44
  renowned healthcare investment firm, very, very reputable.
• 9:48
  They know the space very, very well and serum medicines.
• 9:53
  They were looking for either first in class and or best in
• 9:58
  class medicines, biologics in the immunology and inflammation
• 10:03
  space and they wanted to find an asset that would meaningfully
• 10:08
  improve the standard of care for patients in a chosen disease
• 10:11
  area in the INI space and then create a company and they found
• 10:16
  an asset. Interestingly, they found it
• 10:19
  out. They decided to look in Korea
• 10:22
  and not look in China. You may ask yourself why would
• 10:25
  you do that? And that was because there was a
• 10:28
  if you're going back a few years now, there was a gold rush in
• 10:30
  China. Every big pharma company with
• 10:34
  their big BD cheque books and their big BD teams were there.
• 10:38
  So you could ask yourself how does a three or four person
• 10:40
  incubator like Sera compete with those big BD checkbooks?
• 10:44
  Well, I think the first innovative thing they did and
• 10:47
  brave thing they did was to look in Korea where most companies
• 10:51
  weren't looking at that point in time.
• 10:53
  They found a lot of innovation going on there and that was a
• 10:58
  really, really and and that's where they found the asset.
• 11:02
  So it certainly worked. The second thing I would say is
• 11:05
  the asset itself is a bispecific antibody.
• 11:09
  It's an anti TNF with a box 40 ligand.
• 11:13
  And then the second thing the learning I'd say about how the
• 11:16
  company was formed is when you look at an asset like that on
• 11:20
  surface, a lot of the traditional companies would look
• 11:24
  at that and turn their eyes up at it because it's based on an
• 11:27
  anti TNF. And I think in our industry
• 11:31
  there's a huge bias for the definition of what innovation
• 11:34
  is. And I understand it, which is
• 11:37
  innovation equals brand new medicine, new MOA, moon shot,
• 11:43
  curing a disease or and look, we, we the industry needs that,
• 11:47
  we need that, patients need that.
• 11:49
  But equally innovation can be operational innovation, it can
• 11:53
  be dosing innovation, it can be formulation innovation, it can
• 11:58
  be solving the limitations of an incredible drug from 20 years
• 12:02
  ago that would be even more incredible if you could address
• 12:06
  it's demons. And I think that is something
• 12:09
  that sera and biotech does very, very well.
• 12:13
  And so when you look at the TNF, yeah, it's 25 years old and but
• 12:19
  it's a very, very rapid active monoclonal, but it had some
• 12:22
  challenges. It's difficult to work with and
• 12:24
  difficult to combine and advise specific.
• 12:27
  If you could do that, then you've got a new molecule, it's
• 12:29
  innovation, it's anti TNF typically have a lot of problems
• 12:34
  with ADA's. Can you resolve that ADA
• 12:36
  problem? Then you've got an A new
• 12:39
  improved innovation. And so that's exactly what Sera
• 12:44
  and we thought we could do. And then the other thing it was,
• 12:47
  it was an IV. And as you can imagine in
• 12:50
  today's world, the majority of biologics are all self
• 12:53
  administered subcutaneous injections.
• 12:55
  So instead of just turning the page over or doing swipe left,
• 13:00
  the team thought, you know what, we think our protein engineers
• 13:04
  have got the know how and the capability to work on this IV
• 13:08
  formulation half life, extend it to give it extended dosing and
• 13:13
  at the same time formulate it in a higher concentration so it can
• 13:17
  be administered as a self administered subcutaneous
• 13:20
  injection. So no different to Humira,
• 13:22
  Dupixent, etcetera. And they managed to do that.
• 13:27
  And so I think that's a really cool example of how the small
• 13:30
  company in biotech is able to compete with a large company
• 13:33
  with a bigger team and bigger checkbook.
• 13:35
  Yeah, you got to think outside the box, right?
• 13:37
  And do things in a slightly different way.
• 13:39
  I mean, talk a little bit, if you don't mind, Josh, about the
• 13:43
  area you're going into HS. Why that indication what the
• 13:47
  need is, right? Because like, yeah, for anyone
• 13:49
  who doesn't know HS what the disease is.
• 13:52
  Yeah. So let me talk about Navigator
• 13:56
  and HS together. Yeah.
• 13:57
  So I'll probably mix the two because I think they're we're
• 14:00
  inextricably linked. So Navigator, a mighty team of
• 14:05
  23 Navigator employees as we stand today.
• 14:09
  As I said earlier, the company was formed in August of 2024.
• 14:13
  Back then I was employee number 5 as ACEO.
• 14:17
  So we've had rapid growth in just over a year.
• 14:20
  The company we're focused on 1st in class and or best in class
• 14:25
  biologics in the INI space. Our lead program is NAV 240 and
• 14:31
  NAV 242, which is anti TNF OX40 ligand bispecific.
• 14:37
  The 240 formulation is an IV every four weeks and the 242
• 14:43
  formulation is the one I described earlier that's new and
• 14:46
  it proved to make it innovative in the sense that it's a
• 14:50
  subcutaneous injection and the dosing is going to be every
• 14:53
  eight weeks or every 12 weeks, which is a big, big
• 14:56
  differentiating factor and benefit for patients.
• 15:00
  And the lead indication is HS hidradenitis superativa.
• 15:05
  We're second in class around 1 1/2, two years behind Sanofi,
• 15:10
  but we believe we are potentially best in class on
• 15:14
  three specific points of differentiation versus Sanofi.
• 15:19
  That's probably 2 years ahead of us.
• 15:22
  We believe when you look at our profile we can have best in
• 15:26
  disease efficacy. We believe we have to a large
• 15:30
  part resolve the ADA challenges with anti TNF therapy and that's
• 15:36
  another differentiator. And then I mentioned that dosing
• 15:39
  is a big differentiator because Sanofi's drug is dosed every two
• 15:43
  weeks as will be every eight or every 12 weeks.
• 15:47
  And the fantastic thing about the amazing work that Sanofi
• 15:50
  have done with this thereby specific, they've already
• 15:53
  demonstrated very strong clinical proof of proof of
• 15:57
  concept in HS with some very compelling and very reassuring
• 16:02
  safety results. So you can see why we're excited
• 16:05
  at Navigator about that because we've got an opportunity to
• 16:08
  raise a standard of care with Sanofi and raise a standard of
• 16:13
  care in HS and build on the market and the innovation that
• 16:17
  Sanofi's providing with our own innovation.
• 16:20
  And in terms of why HS, we chose HS because that's this, this
• 16:24
  bispecific combination. There was a lot of evidence
• 16:28
  suggesting it could give incredible results.
• 16:31
  As I said, Sanofi's demonstrated in a phase two study, proof of
• 16:34
  concept, really, really strong results.
• 16:39
  HS is a hidradenite hidradenitis superativa.
• 16:42
  It's a debilitating skin condition.
• 16:45
  It's a heterogeneous skin condition, which means there's
• 16:48
  no there's no well identified or sync or established single
• 16:54
  dominant pathway or biomarker. And you've got a 50% overlap
• 16:58
  with obesity and the word debilitating is often overused,
• 17:05
  but I it's not overused for HS and I say debilitating.
• 17:09
  Imagine you've got sores. I'm trying to use plain like
• 17:14
  that sores. Abscess is not your training
• 17:17
  time, but sores on your skin. Imagine they're painful, imagine
• 17:21
  they're smelly, imagine they leak and they're messy.
• 17:25
  So and then to make things worse, with HS, what I've just
• 17:29
  described to you typically occurs in the genitalia area or
• 17:34
  under the armpits. So you can imagine how how much
• 17:39
  of an impact that has on your ego, your emotional well-being,
• 17:42
  your ability to have an intimate relationship with someone you
• 17:45
  love. How comfortable are you going to
• 17:50
  a doctor and being really candid about the symptoms and what
• 17:54
  you're suffering from? Then how, how, how much of an
• 17:57
  awkward situation is for a poor HS patient and the doctor trying
• 18:02
  to inspect those body parts to understand how serious is their
• 18:06
  disease, what stage is it at? And then deciding what treatment
• 18:10
  is required. So it really is a debilitating
• 18:13
  disease on so many levels. So that's a huge motivation from
• 18:17
  from us at Navigator to help these patients.
• 18:20
  Heterogeneous disease with no established biomarker or no
• 18:24
  pathway means one mode of action.
• 18:27
  A single target mode of action drug is unlikely to be able to
• 18:33
  give the sufficient level of efficacy.
• 18:36
  And the the obesity is important because obese patients, they
• 18:39
  have a higher inflammatory burden and typically they have
• 18:42
  faster drug clearance. Today there are three
• 18:45
  monoclonals that are FDA approved for HS.
• 18:49
  All of them are subcutaneous formulations as I mentioned
• 18:52
  earlier, and they're all dosed either Q1 week, Q2 week or Q4
• 18:56
  week. So with a Q8 or Q12 week
• 18:59
  product, we are highly differentiated on dosing alone.
• 19:03
  But like I said, we've got three points of differentiation, not
• 19:05
  just dosing. The three drugs that are
• 19:08
  approved today are Humira, Cosentyx and Bims addicts and
• 19:13
  there's a lot of intravenous infliximab that's used off
• 19:17
  label. That's used off label because I
• 19:19
  said earlier, a lot of these patients are heavier and with an
• 19:22
  IV you can do weight based dosing and push the dose up to
• 19:25
  push up the drug exposure. So that's why doctors are using
• 19:30
  infliximab off label. And then with the three
• 19:35
  monoclonals, an efficacy ceiling has been reached and we look to
• 19:39
  all the efficacy data and only 30%, maybe just over 30% of
• 19:45
  patients achieve high score 75, which is the established
• 19:49
  regulatory and efficacy endpoint for HS.
• 19:52
  Only around 3030, two, 3334% of patients achieve that efficacy
• 19:58
  response versus baseline. So that means you got six to
• 20:01
  seven out of 10 patients not getting sufficient benefit, so
• 20:05
  we believe. That combination therapy, which
• 20:08
  includes by specific antibodies are going to be required to
• 20:12
  break the efficacy ceiling. And this was a key topic at the
• 20:15
  AAD Congress in Denver a few months back.
• 20:18
  That combination therapy is going to have to be the path
• 20:20
  forward to break the efficacy ceiling.
• 20:23
  And like I said, when you look at the amazing work Sanofi have
• 20:25
  done with their Phase 2A proof of concept, they delivered a
• 20:30
  best in disease 54% efficacy response versus baseline.
• 20:36
  So you've got far over 5 out of 10 patients compared to three
• 20:40
  out of 10 patients with the existing therapy.
• 20:42
  So that's why we're super excited about what we're doing.
• 20:45
  Yeah, nice. Thanks.
• 20:46
  And that's a usual insight as to the current standard of care as
• 20:49
  well. You, you mentioned Sanofi and
• 20:51
  and obviously, yeah, wee bit ahead of you guys in in the
• 20:55
  clinic. Do you want to talk to us a
• 20:57
  little bit about where you guys are at in the clinic and how are
• 20:59
  you hoping to? Yeah.
• 21:01
  Maybe catch up a bit and go back to that point and go big pharma
• 21:05
  versus versus biotech? Yes, you're right.
• 21:08
  So we're all so, so the status of our the stage of our
• 21:12
  programme. So NAV 240 that's the once a
• 21:15
  month IV formulation with that we are, we are in phase, we are
• 21:21
  dosing phase two patients. So we've got 150 patients study
• 21:26
  that began in February and it's a placebo-controlled study.
• 21:31
  We're studying 2 doses of this IV formulation and that's slated
• 21:35
  to give results end of third quarter 2027.
• 21:39
  Recruitment is going really well and we're super excited about
• 21:42
  the execution of that study. Now in parallel, not
• 21:47
  sequentially, really important point.
• 21:49
  In parallel, we're doing a phase one study that's dosing healthy
• 21:54
  volunteers in Australia with NAV 242.
• 21:59
  That is our subcutaneous every eight or every 12 week
• 22:04
  formulation. So we are doing both those
• 22:08
  studies in parallel and not sequentially.
• 22:12
  We're doing that because that's a way to try to catch up with
• 22:16
  Sanofi and just generally in biotech do things a little bit
• 22:20
  quicker so you get your eventual drug should it get approved to
• 22:25
  these patients quicker. So that's another example of us
• 22:28
  taking a smart risk. I will say that when you do,
• 22:33
  when you do studies in parallel, that does increase your
• 22:36
  financial burn rate. So it means that we're spending
• 22:39
  more money and we're spending it more quickly in order to
• 22:42
  accelerate. And so you, you just got to make
• 22:45
  sure you've got the support of your board and your investors in
• 22:49
  your clinical development programme and we absolutely do.
• 22:52
  So that's one thing we're doing to try to catch up with Sanofi
• 22:56
  and more importantly get this medicine to patients as quickly
• 22:59
  as possible. The second thing we're doing is
• 23:03
  once we complete this early, this phase one, phase two
• 23:07
  programme, when it comes to our pivotal registrational
• 23:10
  programme, there we are. Our current thinking is we are
• 23:17
  highly, highly likely to do a contiguous Phase 2B phase three
• 23:24
  study as opposed to doing a stand alone Phase 2A proof of
• 23:29
  concept, a stand alone phase 2B dose ranging and a stand alone
• 23:35
  pivotal phase three registration program.
• 23:37
  If you can do the phase 2B and phase three is 1 adaptive study,
• 23:42
  you can save anything from 6 to 9 to 10 months.
• 23:47
  So that's another way that in a biotech, you can do things that
• 23:52
  are non traditional, do things differently, always in
• 23:56
  consultation with the regulators.
• 23:58
  And that's another way to catch up with the competition in which
• 24:01
  in this case, the no FIFA Navigator.
• 24:04
  But like I said, stepping back more importantly, to shrink the
• 24:07
  time between this innovation that will become a medicine
• 24:11
  hopefully and then get onto pharmacy shelves so it can help
• 24:14
  patients. So they're 2 examples of how
• 24:17
  we're closing the gap competitively, getting the drug
• 24:21
  to patients more quickly. And I think it's a great example
• 24:24
  of how a small start up company can be more agile and be more
• 24:29
  creative and do some things that maybe larger companies are not
• 24:34
  willing to do or they're unlikely to do for a whole range
• 24:37
  of reasons. Yeah, 100%.
• 24:39
  You've got to take advantage of that capacity to be flexible,
• 24:43
  right? Otherwise, what's the point?
• 24:44
  And having it, you may as well have the safety net that we
• 24:46
  discussed earlier, for sure. That's right.
• 24:49
  Nice. And then just generally on, on
• 24:51
  timelines, when are you expecting some more data from
• 24:54
  the program? Is that later this year or?
• 24:57
  So our proof of concept, our Phase 2A proof of concept in HS
• 25:02
  patients that will deliver top line results towards the end of
• 25:06
  third quarter next year, so third quarter 2027.
• 25:10
  And then in parallel with the Phase one program that we're
• 25:13
  doing with our subcutaneous Q12 week or Q8 week formulation,
• 25:18
  we'll get results from that study on an ongoing basis.
• 25:22
  There'll be some data at the end of this year and then some more
• 25:25
  data in Q1, Q2 2027. And then with that phase, with
• 25:31
  that Phase 2 proof of concept data, with the IV, with the
• 25:35
  Phase one data from a subcutaneous formulation, we'll
• 25:39
  do a bridging analysis, not a bridging study, but a bridging
• 25:43
  analysis to make sure we get the exposure right with our
• 25:47
  subcutaneous formulation, so it can at least match or exceed
• 25:51
  what the IV is doing. And then we'll take the
• 25:54
  subcutaneous formulation into the into the pivotal
• 25:57
  registration program. So look, I mean, if all things
• 26:00
  go to plan, they really do because you get bumps along the
• 26:03
  road. But if you take some standard
• 26:05
  benchmark timings, if you look at some of the accelerated
• 26:09
  timings because of the, the, the, the smart more agile way
• 26:13
  we're going to do some of these studies.
• 26:15
  We think that it's realistic with what we know today that the
• 26:19
  BLA could be filed as early as second-half 20-30, but more
• 26:24
  likely first half 2031, which would be very much in line with
• 26:28
  our estimates of where of where Sanofi would be as well, which
• 26:32
  is if we can achieve that, there'll be a huge feat for our
• 26:36
  part because like I said, we're 20, only three people.
• 26:38
  We're currently sitting two years behind Sanofi.
• 26:40
  So to be on their coattails or two or three months behind them,
• 26:44
  that'll be yeoman's work by the Navigator team.
• 26:47
  Yeah, it'll be pretty impressive.
• 26:49
  And I guess just the final point, like you've obviously
• 26:52
  been with the business a couple years now and you've seen it
• 26:55
  grow massively in that time, albeit the team's really small.
• 27:00
  I guess just a question to finish up on Tosh.
• 27:02
  Like is there anything that you know now but you wish you'd
• 27:05
  known at the start? And if so, how would you sort of
• 27:07
  implement it at the start? Oh my goodness.
• 27:11
  Yeah. Look, I'm a first time CEO.
• 27:13
  So before I took the job, I spoke to many colleagues and
• 27:17
  friends who had been first time CEO's of biotech startups to try
• 27:21
  and learn as much as I could from them.
• 27:24
  And the one thing that they told me but I didn't fully
• 27:29
  appreciate. But now that I'm in the job, I'm
• 27:31
  like, whoa, my goodness, now I know why they were telling me.
• 27:34
  This is the amount of time I spend externally with the
• 27:40
  investment community. So I'm talking about investors,
• 27:44
  VCs, banks, that whole ecosystem.
• 27:47
  My goodness, it is a huge part of my job.
• 27:50
  It really is. And even though I was warned,
• 27:53
  but warned is the wrong word, even though I was given a heads
• 27:55
  up about that, it didn't really sink in.
• 27:57
  I spent so much of my time doing it.
• 28:00
  And by the way, I'm not saying that as a complaint.
• 28:04
  It's just it's a big part of the job and I actually love it
• 28:07
  because a large part of my job as ACEO is always be selling.
• 28:13
  What am I selling? I'm selling our program and I'm
• 28:17
  selling the people who are executing the plan to get this
• 28:22
  drug through the development pathway and ultimately to
• 28:24
  patients. So, yeah, I'm always selling our
• 28:27
  program, I'm always selling our people to the investment
• 28:30
  community and it's really making sure our existing investors, I
• 28:35
  want to make sure we give them continued confidence that their
• 28:39
  funds that they've given to us, we are deploying them
• 28:42
  appropriately in an efficient, responsible manner that's going
• 28:47
  to get us to the next milestone or the next important event that
• 28:52
  unlocks on value and demonstrates progress.
• 28:55
  And equally, I'm always selling to potential new investors.
• 28:59
  I like to say a big part of my job is to give new investors who
• 29:02
  haven't invested in Navigator, I want to give them FOMO.
• 29:06
  I want to give them big time FOMO.
• 29:08
  That's my job. And I want to make them want to
• 29:10
  invest in US in any future financing.
• 29:13
  So I it's a huge part of my job. And this telling or selling of
• 29:19
  the Navigator story, I have to do it again and again and again
• 29:23
  ad nauseam. It's never ending, but I love
• 29:25
  it. I really do.
• 29:26
  I mean, what's up to love? I get to our amazing lead
• 29:29
  programme, our amazing science and how we're going to help HS
• 29:33
  patients and deliver potentially a best in class medicine with
• 29:37
  best in class dosing, best in class efficacy.
• 29:40
  And at the same time, I guess my favorite part of the job is I
• 29:43
  get to show off the amazing work of the team.
• 29:45
  I had the pleasure and privilege of leading, working with and
• 29:49
  learning from. So I'm happy as Larry Callum
• 29:52
  doing this job. I really AM.
• 29:54
  And you're not doing a bad job of selling the story as well,
• 29:56
  Tosh. So all good.
• 29:57
  Well, look, it's been a pleasure to have you on.
• 29:59
  And yeah, looking forward to keeping an eye on Navigator over
• 30:03
  the next few years for sure. Thank you, Callum.
• 30:05
  I've enjoyed the conversation. Yeah, Cheers, Dosh.