Latest / The BioHub - by Avetix / Episode 69 - Nolan Townsend - CEO of Lexeo Therapeutics

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Episode 69 - Nolan Townsend - CEO of Lexeo Therapeutics · The BioHub - by Avetix

• 0:04
  So welcome back to your episode of the Bio Hub.
• 0:07
  Today, we're delighted to welcome Nolan Townsend, a
• 0:09
  seasoned biotech leader and the CEO of Lexio Therapeutics.
• 0:13
  With a background that spans investment banking and executive
• 0:16
  leadership at Pfizer, when Nolan led the rare disease division
• 0:19
  globally, Nolan brings a unique blend of financial insight and
• 0:23
  clinical innovation. Lexio Therapeutics are a
• 0:26
  clinical stage biotech based in New York focused on improving
• 0:29
  hearts health by using cutting edge science to change how we
• 0:33
  treat genetic heart diseases. So join us today as we'll talk
• 0:37
  through Nolan's journey, Lexio's pipeline, as well as what's next
• 0:41
  for Lexio Therapeutics. Thanks so much for coming on.
• 0:45
  How are you? I'm great.
• 0:46
  It's great to. It's great to be here today.
• 0:49
  Yeah, it's a pleasure to have you on.
• 0:51
  So thanks for thanks for helping us out.
• 0:53
  So look, let's start with a little bit about yourself then.
• 0:56
  So you began your career in healthcare finance before
• 0:59
  transitioning into leadership roles at Pfizer and now Lexio.
• 1:04
  What drew you into the life sciences industry and what
• 1:06
  inspired you to join Lexio as CEO?
• 1:10
  That's a good question. You know, I think in general, I,
• 1:15
  I felt that one of humankind's greatest innovations is the
• 1:19
  ability to, you know, extend our, our own lives with, with
• 1:22
  technology, you know, and imagine being able to package
• 1:26
  this, this technology into a pill or into a vial.
• 1:31
  You know, the concept of that was, was very attractive to me.
• 1:33
  I, I see it as, you know, the, the type of industry that would,
• 1:36
  would always exist. I think humankind wants to live
• 1:39
  longer, wants to live healthier lives.
• 1:41
  And, you know, this is the industry that's delivering, you
• 1:44
  know, solutions, you know, to, to that challenge.
• 1:48
  So as we, as we evolve as a, as a, let's say, as a species, you
• 1:53
  know, we'll always find some, some new disease, some new
• 1:57
  challenge from a healthcare perspective that we're seeking
• 1:59
  to address. And I think therapeutics are,
• 2:01
  you know, the most efficient way to address the, the challenges
• 2:05
  of, of, of extending life. So that's what drew me to the
• 2:09
  industry in general. You know, I started my career in
• 2:14
  finance. You know, maybe it's because of
• 2:16
  where I went to undergraduate. I went to University of
• 2:18
  Pennsylvania. It has a very strong, you know,
• 2:22
  sort of finance, you know, flow from, from Penn to, to New York
• 2:26
  and and so on. And I, you know, worked in
• 2:30
  corporate finance and, and then later in, in healthcare
• 2:33
  investment banking and as, as I, you know, was in investment
• 2:37
  banking. I, I worked on, you know,
• 2:38
  various transactions and I saw that, you know, a lot of the
• 2:42
  decision makers for the transaction itself and the
• 2:45
  individuals that were responsible for, you know,
• 2:48
  realizing the full value of whatever that transaction was,
• 2:51
  were some of the, you know, operating executives or general
• 2:54
  managers, the CEOs of the companies that we were, you
• 2:56
  know, working with. So that was 1, you know,
• 2:59
  important exposure or learning for me was, was that that
• 3:03
  dynamic? I also for my, the graduate
• 3:07
  education went to Harvard Business School, which is a
• 3:10
  general management school. So, you know, you hear a lot
• 3:12
  from, you know, CEOs, you know, in that context, a lot of the
• 3:17
  case studies that that we would spend time with in, in at
• 3:20
  Harvard Business School, the protagonist of the case is our
• 3:24
  CEO. So you get to see things, you
• 3:26
  know, from the vantage point of ACEO and I think you have a full
• 3:29
  understanding of the complexity of the role and also the impact
• 3:33
  that such a role can have on, on organizations, on industries,
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  you know, and so on. So, you know, leaving investment
• 3:40
  banking, I, I took a path, you know, working at Pfizer towards,
• 3:45
  you know, more general management or operating roles
• 3:48
  that led to a, you know, successive stream, stream of
• 3:52
  general management roles both in and outside of the US.
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  The last few of which, as you mentioned were and Pfizer's rare
• 3:58
  disease business, which actually exposed me to the, you know,
• 4:02
  potential of, of genetic medicines and the impact of
• 4:06
  treating, you know, complex rare diseases with the time I'm at
• 4:09
  need. And so I think this was a lot of
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  the backdrop for the formation of Lexio and then the focus of
• 4:15
  the company. And, and I think that that's an
• 4:18
  important aspect of of the work that we're doing across the the
• 4:21
  biotechnology industry. Yeah, good.
• 4:25
  And just a little bit into Lexia then.
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  So I guess the company has evolved since its founding,
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  expanding from a gene therapy focus company into a broader
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  clinical stage biotech. How has the company's mission
• 4:37
  and scientific vision changed under your leadership, and how
• 4:41
  is the pipeline matured as a result?
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  Of that, yeah. So it's, it's, it's, it's an
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  interesting story. We're almost a six year old
• 4:48
  company now. If you look back at our first,
• 4:52
  you know, press releases, you would see that we had an, an
• 4:55
  option to 18 different gene therapies and these sat across,
• 5:01
  you know, 5 different therapeutic areas.
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  So that was, you know, the, the pipeline we theoretically had
• 5:07
  access to at the outset of the company.
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  You know, at that time we, we decided to focus primarily on
• 5:13
  cardiac and central nervous system diseases.
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  We did not spend much time on some of the other, some of the
• 5:19
  other disease areas. And then, you know more recently
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  have even further narrowed our focus to to cardiac.
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  And I think there's a few things that sit behind that.
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  You know, admittedly one of them is the capital markets
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  environment. I think it forces companies to
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  really focus on, you know, the programs with with the highest
• 5:38
  probability of success that will have the highest impact for, you
• 5:40
  know, for patients. But what that also implies what
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  what I mentioned high probability of success is, you
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  know, focusing on places where you can demonstrate the, the
• 5:49
  value of the program, both the patients, payers, investors and
• 5:53
  so on, you know, on a more rapid time frame.
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  So this would mean focusing on diseases where, you know, maybe
• 6:00
  the biology is more well understood.
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  So mean focusing on diseases where you can, you know,
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  demonstrate, for example, you know, tissue transduction via
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  tissue samples. You could take a tissue sample
• 6:13
  of the heart, for example. You cannot take a tissue sample
• 6:16
  of the brain where the biomarkers for the disease are
• 6:19
  are well understood or there may be regulatory pathways that are
• 6:23
  more clearly defined. So I think that's, you know, the
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  kind of series of considerations that in part LED us to focus on
• 6:30
  cardiac, but the other side of it is just the degree of unmet
• 6:34
  need. I mean, today there were, you
• 6:37
  know, fewer than 10 cardiac precision medicines that have
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  been approved. You know, there's a reason for
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  that. I think historically the FDA is
• 6:46
  required cardiovascular outcome studies with with heart
• 6:49
  endpoints to support the approval of cardiovascular
• 6:52
  treatments. But this has been evolving over
• 6:54
  the past few years and the FDA has become open to, you know,
• 6:57
  biomarker based endpoints which open the door to, you know, rare
• 7:02
  and precision medicines in in cardiovascular disease.
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  Myself and a few members of our team, management team and
• 7:10
  broader team at Lexio had the opportunity to lead the launch
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  of I think one of the first cardiovascular rare disease
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  treatments at at Pfizer. This was to feminist for the
• 7:21
  treatment of TTR amyloid cardiomyopathy.
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  And I think this really opened our, our eyes and frankly the
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  eyes of, of the entire biotechnology industry to the
• 7:31
  potential of cardiac rare disease treatments.
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  We have a number of companies that have since launched
• 7:38
  competitive treatments to the, the one that we that, that we
• 7:41
  launched and developed there, you know, a couple of years
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  back. So I think the question is, you
• 7:45
  know, what's next for rare and precision cardiac medicine.
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  And in our view, the AV vector is the most efficient way to
• 7:53
  deliver genetic payloads to the heart.
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  Lipid nanoparticles cannot access the cardiomyocyte Gownak
• 8:00
  you know, and so on are not able to to deliver those kinds of
• 8:03
  payloads to the heart. So, you know, for the moment we
• 8:06
  think this is the most efficient way to treat, you know, cardiac
• 8:08
  kinetic disease. This may not always be the case.
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  I think other you know, modalities including non viral
• 8:15
  will emerge to treat genetic conditions of the heart.
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  But you know, today Lexio has two clinical stage programs that
• 8:21
  are moving rapidly and diseases of high unmet need.
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  The first being in Friedrich's ataxia where we're treating both
• 8:29
  the cardiac and neurologic symptoms of the disease, and the
• 8:32
  second being an arrhythmogenic cardiomyopathy.
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  I think these are good examples of the potential of genetic
• 8:38
  medicines in, in cardiac disease.
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  I'd expect that, you know, the, the next wave of treatments
• 8:43
  will, you know, redefine what it means to treat cardiac disease.
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  And, and what I mean by that is, you know, today we look at, for
• 8:50
  example, heart failure, HEPFPF or HEPF ref as one uniform,
• 8:54
  almost monolithic disease. But the belief is that as you
• 8:58
  look at the genetics that sit behind a disease like this, you
• 9:02
  may find that the genetics are, are, are a driver of the
• 9:05
  disease, similar to what we found in oncology.
• 9:08
  And so the therapeutic solutions mean breaking the disease into
• 9:11
  its genetic components and then applying, you know, precision
• 9:14
  therapies to to treat each of those, you know, genetically
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  driven components of a of a much broader disease.
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  If I'd expect the cardiovascular disease is ultimately looks a
• 9:23
  lot like oncology. We'll see a range of treatments
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  to to address these, you know, genetically mediated
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  cardiovascular conditions. I think AV vectors and gene
• 9:35
  therapy will will be the tip of the spear here, but I think
• 9:39
  we'll ultimately see other modalities emerge that that will
• 9:42
  be in a position to treat cardiac disease.
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  And we we've done some preclinical work in, in non
• 9:47
  viral, for example, RNA for treating cardiac disease will be
• 9:51
  formed a new company with two leading venture funds to
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  continue to explore that that pathway.
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  So I think there's more to come on that front.
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  But today our clinical stage programs are, I believe really
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  tip of the spear for the treatment of genetic diseases
• 10:06
  with with with gene therapy. Nice.
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  And just to delve into Lexio's cardiology pipeline, so the two
• 10:13
  league program, so LX2006 and LX2020 targeting genetic forms
• 10:21
  of cardiomyopathy. Can you share more about these
• 10:24
  therapies, the specific conditions they're designed to
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  treat, as well as the unmet clinical needs that they would
• 10:31
  address? Yeah.
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  So the most advanced program is treating Friedrich's ataxia.
• 10:37
  This is a multi system disease. And what I mean by that is you
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  would typically think of Friedrich's ataxia as a
• 10:43
  neurologic disease and then that's the the ataxia component
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  of it. This disease typically develops
• 10:49
  in childhood. These are patients that are 5,
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  you know, 8 years old that the neurologic disease progresses
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  typically into a form of cardiomyopathy, emerges in in
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  adulthood. And it's this cardiomyopathy
• 11:01
  that's typically the cause of death for the majority of
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  Friedrich's ataxia patients. And typically patients
• 11:07
  experience mortality in their in the third decade of life.
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  So a therapeutic that can treat both the cause of mortality in
• 11:14
  this disease, which is cardiac, but can also have some benefit
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  in the neurologic disease, is one that, you know, we believe
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  would be highly valued by patients that are, you know,
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  that are, that are suffering from Friedrich's ataxia.
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  So this therapy was is designed to deliver a functional copy of
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  the miss of the missing gene, which is for toxin deliver it
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  expresses the functional protein by re expressing for this for
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  toxin protein. This this has been shown to
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  reverse the disease cardiac disease pathology in terms of a
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  reducing, you know, heart mass, which is the series of events
• 11:51
  that ultimately leads to to heart failure.
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  We've also shown some benefit in the neurologic component of the
• 11:56
  disease on certain Friedrichs ataxia, your functional scales.
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  So this is a disease of, you know, high unmet need.
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  There is an existing therapy, but this therapy only treats the
• 12:08
  neurologic component of the disease.
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  It it does not appear to have a benefit for the cardiac disease.
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  So, you know, many patients will still die from, from this
• 12:15
  disease without a therapy like one that we're developing that
• 12:19
  that can address the cardiac component.
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  So we're excited about this therapy.
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  It's, it's moving rapidly into registrational study.
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  We'd hope to have data from this registrational study in 2027 and
• 12:30
  then be submitting ABLA thereafter.
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  So I think it's not too distant that we could see an additional
• 12:36
  therapeutic option for patients with with Friedrich's ataxia.
• 12:40
  The next most advanced program as you mentioned is, is treating
• 12:43
  arrhythmogenic cardiomyopathy. This is a very different disease
• 12:46
  pathology. It's a disease of arrhythmia of,
• 12:49
  of life threatening arrhythmias. Commonly patients experience,
• 12:53
  you know, sudden death from this disease.
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  It's electric basic electrical conduction disorder.
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  This disease is mediated by a deficiency in the in the
• 13:03
  mutation the in the placophyllin 2 gene, which is the most common
• 13:07
  gene associated with arrhythmogenic cardiomyopathy.
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  This gene mutation causes deficiency of the functional
• 13:14
  protein. We're restoring the the genetics
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  and then the the functional protein is expressed through
• 13:20
  that restoration. This has been seen in animal
• 13:23
  models to correct the disease pathology, produce these life
• 13:28
  threatening rhythmic events and and address other symptoms of
• 13:31
  the disease. This is a relatively large, rare
• 13:34
  disease. It's about 60,000 patients in
• 13:36
  the US. So I think a therapeutic option
• 13:39
  that has a, you know, meaningful impact and the right safety
• 13:42
  profile could address a, a pretty significant cause of
• 13:45
  mortality and morbidity in, in this important, you know,
• 13:49
  cardiac disease. So these are the two therapies
• 13:52
  that we're we're developing. The second one, the rhythmogenic
• 13:56
  cardiomyopathy program, will have a data readout from our
• 13:59
  phase one study in the second-half of of this year.
• 14:04
  Exciting. I know gene therapy has
• 14:07
  traditionally been applied to rare diseases, but Lexio are
• 14:10
  applying this to cardiovascular conditions.
• 14:13
  What do you think makes the gene therapy space A promising
• 14:16
  strategy, and how does it compare to more traditional
• 14:20
  treatment approaches? Well, I'd say first, you know,
• 14:23
  these are both cardiac, but they're also rare.
• 14:26
  So the, the 2 are not necessarily mutually exclusive.
• 14:29
  But you know, I, I think importantly, historically gene
• 14:32
  therapies have been applied to, to liver mediated diseases.
• 14:37
  And so these were, for example, the hemophilia treatments,
• 14:41
  they've been applied to ocular diseases.
• 14:43
  So Luxterna, the commercially approved gene therapy is a, is a
• 14:47
  is eye disease and then has been applied in the case of spinal
• 14:51
  muscular atrophy to a disease to a, to a neurologic disease, but
• 14:57
  it has not been applied at least has not reached a commercial
• 15:00
  setting or late stage studies even into endocardiac disease.
• 15:05
  And I think that's unique and I think the heart is uniquely
• 15:09
  amenable to, to gene therapy in a, in a few ways.
• 15:13
  One is that we have found the delivery system or the vector
• 15:18
  that can deliver genetic payload to the heart, but do so at, at,
• 15:21
  at safe doses. And this is an important theme
• 15:25
  here that we've been able to at relatively low doses, for
• 15:28
  example, in our Friedrich ataxia study achieved very, a very
• 15:31
  meaningful effect size and improvement of cardiac
• 15:34
  hypertrophy and, and other, you know, symptoms of, of, of
• 15:38
  cardiomyopathy. Secondarily, it is actually in,
• 15:43
  in, in in one sense almost ideal for the the case of clinical
• 15:48
  trials and that there are, you know, non invasive biomarkers
• 15:51
  you can use to assess the progression or regression of
• 15:56
  cardiac disease. For example, cardiac MRI echo.
• 16:00
  There's blood based biomarkers like troponin that can evaluate
• 16:03
  A cardiac cell death. So there's a number of non
• 16:06
  invasive ways to evaluate disease progression.
• 16:09
  You can also take tissue samples of the heart, which you, you
• 16:12
  know, cannot necessarily do in the in the brain or the eye, for
• 16:14
  example. But importantly, then this is
• 16:18
  obviously the type of diseases that result in mortality.
• 16:22
  And, you know, cardiac disease is one of the leading causes of
• 16:25
  mortality, you know, globally. And you can look at
• 16:29
  hospitalization, you can look at, you know, symptoms of heart
• 16:32
  failure, shortness of breath. I mean, there's a number of
• 16:34
  different and really meaningful clinical endpoints, you know, in
• 16:38
  some cases hard endpoints that you can evaluate.
• 16:40
  So I think we have a range of of tools available to us when we're
• 16:44
  designing clinical trials that can allow us to, you know,
• 16:47
  rapidly advance these therapies through development.
• 16:50
  And as I mentioned earlier, the FDA is, is open to these
• 16:53
  biomarkers as, as, as accelerated approval endpoints.
• 16:58
  And so I think we will find ourselves in a place where we
• 17:01
  can begin to see the potential of precision or rare cardiac
• 17:05
  treatments through, through therapies like we're developing.
• 17:09
  I would expect others to begin to, you know, focus on this as
• 17:12
  well over time. Yeah, and the cell and gene
• 17:17
  therapy fields has experienced both significant breakthroughs
• 17:21
  as well as definitely some recent headwinds.
• 17:24
  What gives you confidence in cell and gene therapies?
• 17:26
  Long term potential? Yeah, it's a, it's a good
• 17:29
  question and, and I think an important one right now.
• 17:32
  And, and I would, you know, make the case that every new novel
• 17:36
  modality, whether you look back at, you know, monoclonal
• 17:39
  antibodies, you look back at, you know, RNAI, you know, all
• 17:44
  modalities kind of go through periods of, of, of excitement
• 17:49
  and, and, and, and investment and, and a lot of interest.
• 17:52
  And, and then, you know, may experience some setbacks as they
• 17:57
  move through, you know, clinical development, maybe early
• 17:59
  commercial. And, and I think the field
• 18:02
  begins to understand, you know, some of the challenges of, of
• 18:05
  the modality. And I think we've spent the last
• 18:07
  few years in gene therapy really understanding some of the
• 18:10
  limitations or challenges of, of, of the, of the modality
• 18:13
  itself. And I think there are a few
• 18:14
  important things, you know, that, that we've learned.
• 18:17
  The 1st is that it, it appears that there is a limiting dose to
• 18:21
  gene therapy, meaning this upper end of how much a virus, even of
• 18:26
  this non pathogenic virus that the human body can ultimately
• 18:30
  accept, You know, interestingly, and one of the challenges is
• 18:32
  that some of the diseases of high end summit need, you know,
• 18:35
  require the most, the highest genetic payloads to correct
• 18:38
  them. For example, if you see disease
• 18:40
  like Duchenne's muscular dystrophy, you know, you're,
• 18:43
  you're trying to correct the genetics of, of, of muscles.
• 18:48
  This is the largest organ in, in the human body.
• 18:51
  So you're, you're really skating on the, the edge of, you know,
• 18:53
  what may be a, a, a safe dose for gene therapy relative to the
• 18:58
  need to correct, you know, to correct the disease.
• 19:01
  But I believe if you, you know, were to ask Duchesne's patient
• 19:04
  or the family of a Duchesne's patient, do you want the
• 19:07
  biotechnology industry to explore a therapeutic option,
• 19:10
  despite the fact that it will require a high dose of gene
• 19:13
  therapy, which may come with, you know, a risk benefit profile
• 19:16
  that needs to be, you know, considered.
• 19:17
  I think most, most patients, most families would say,
• 19:20
  absolutely you should pursue a therapy for Duchenne's muscular
• 19:23
  dystrophy, even at even at those doses.
• 19:25
  And so I think that's one of the challenges that we're seeing in
• 19:28
  the field is that some of the diseases we're seeking to
• 19:29
  address are themselves just fundamentally, you know, life
• 19:32
  threatening. And yet, you know, developing A
• 19:35
  therapeutic for them, while it may have, you know, some safety,
• 19:38
  you know, baggage tied to it ultimately is going to have a
• 19:40
  very dramatic, substantial positive benefit for patients
• 19:45
  that are treated with, with the therapy.
• 19:48
  Now, I think the, the, the nuance here is to find the
• 19:53
  right, the, the right tool for the, the, for the disease that
• 19:58
  we're, you know, seeking to treat.
• 20:00
  And I think that's an important theme here is the the evolution
• 20:04
  in the vector technology. Evolution and manufacturing
• 20:07
  technology and so on can allow us to be more precise in the
• 20:11
  tool that we choose to address the disease in question.
• 20:14
  And you know, what we've been able to do in cardiac disease is
• 20:17
  find a capsid that has a high tropism profile or let's say
• 20:20
  affinity for the heart. And that capsid then allows us
• 20:24
  to deliver these, this genetic payload, but do so at lower
• 20:27
  doses. And therefore we can do so, you
• 20:29
  know, very safely, you know, safety in gene therapy is, is
• 20:33
  always related to dose. So when you see a higher dose
• 20:36
  gene therapy, you, you, you know that you're probably accepting
• 20:39
  some safety risk. But as the doses decrease, it's
• 20:41
  actually notable in the absence of, of safety events.
• 20:44
  For example, if you look at, you know, the, the hemophilia
• 20:47
  treatments or other others at, at lower doses.
• 20:50
  So that's the key to the future of the field is to find ways to
• 20:53
  treat the diseases of, of interest and a focus and of, of
• 20:57
  unmet need for society, but do so at at lower doses.
• 21:01
  It's either, you know, reapplying existing, you know,
• 21:04
  vector technology in, in a, in a different way, or, you know,
• 21:08
  there's a, there's a, you know, a huge body of work in novel,
• 21:11
  novel caps that are novel vectors that are seeking to find
• 21:14
  ways to deliver these genetic payloads at, at lower doses.
• 21:17
  So I would see that as the future of gene therapy.
• 21:20
  I think as we achieve that, we'll, we'll see the safety
• 21:22
  profile become something more appropriate even for, for larger
• 21:26
  diseases over time. And I think that's, you know,
• 21:29
  that's where the field is, is headed.
• 21:30
  So I think that's our, our, you know, our, our, our point of
• 21:33
  view on this. Now, the other side of this all,
• 21:36
  and we talked, I talked about safety, but I mean the, the
• 21:39
  efficacy, the, the benefit to patients of gene therapy is, is
• 21:43
  almost, you know, undeniable. You see in sickle cell, you see
• 21:48
  in spinal muscular atrophy. I mean in spinal muscular
• 21:51
  atrophy, this is a disease where, you know, life expectancy
• 21:54
  in SMA, one would typically be, you know, two or three years of
• 21:57
  age, there's patients being treated with the gene therapy
• 21:59
  that are, you know, kind of going on to live a normal life.
• 22:02
  I mean, this is, you know, an unheard of degree of scientific
• 22:06
  and clinical innovation that's being applied to a disease that,
• 22:09
  you know, you know, ultimately would be very challenging for,
• 22:12
  you know, for families and patients.
• 22:14
  So that's the potential of gene therapy.
• 22:15
  That's the potential that's, you know, still yet to be realized
• 22:18
  across, you know, a range of, of rare genetic diseases, but then,
• 22:22
  you know, potentially over time into, into other types of
• 22:25
  diseases. And I would note that, you know,
• 22:28
  because it's a correction of the genetics, you'd expect to see
• 22:32
  persistent expression of the gene therapy in, in, you know,
• 22:35
  in most cases. And so this, these are typically
• 22:38
  one time, you know, one time therapies in some cases could be
• 22:43
  functional cures to the diseases that the that the companies or
• 22:47
  investigators are, are, are seeking to treat.
• 22:49
  So I think this is exactly what society, you know, wants from
• 22:54
  the biotechnology industry is for us to deliver cures to
• 22:57
  diseases, to move away from, you know, treatments that a patient
• 23:00
  has to, you know, has to consume or take for the, you know, for
• 23:05
  the rest of their lives to a single administration, you know,
• 23:08
  functional cure to, to a disease.
• 23:11
  This is what gene therapy can deliver to society over time.
• 23:15
  I just think we have to continue to work on the technology,
• 23:17
  optimize it. We'll have to continue to work
• 23:19
  to make it better. Today.
• 23:21
  I think it's, it's a great technology to apply to, to a set
• 23:25
  of, you know, rare genetic diseases.
• 23:27
  But over time, I think we'll expand the number of diseases
• 23:29
  that we can treat and we'll expand it, you know, potentially
• 23:32
  beyond even the the rare disease context.
• 23:36
  Yeah, very good. I think given today's evolving
• 23:40
  macroeconomic and regulatory environment, how are you
• 23:43
  adapting Lexio's strategy to remain focused and agile while
• 23:47
  continue to advance key programs?
• 23:50
  Yeah, I think the, you know, the macroeconomic environment is an
• 23:52
  important one. You know, obviously the the
• 23:55
  biotechnology market has been, you know, relatively stagnant or
• 24:00
  from a public markets perspective for a number of
• 24:03
  years now. So I think what this means is
• 24:07
  that for companies like us, clinical stage companies we're
• 24:10
  operating, we have to access the capital markets at very, very
• 24:15
  high cost of capital. This means that the the hurdle
• 24:18
  rate for the return on that capital is, is quite high.
• 24:23
  This means that we need to then focus on the programs with the
• 24:26
  highest probability of success or the most attractive, you
• 24:29
  know, market opportunity. That most attractive market
• 24:32
  opportunity would typically mean a disease that does not have an
• 24:35
  existing treatment ahead of it. So I think that's one of the
• 24:38
  important themes is the reason why we've, you know, we really
• 24:41
  refocused our pipeline on our two, you know, say most advanced
• 24:44
  programs that you know, we believe have the highest
• 24:47
  probabilities of success. You know, what comes hand in
• 24:50
  hand with that is the regulatory landscape.
• 24:53
  There has been some volatility on that front in the recent
• 24:56
  months that I think you know most people have have observed
• 25:00
  this volatility, you know does find its way ultimately into the
• 25:04
  cost of capital. So as volatility and uncertainty
• 25:07
  in the regulatory front, then, you know, the cost of capital
• 25:10
  goes up, you know, for companies.
• 25:12
  So I think that it, it really comes down to, to focus to
• 25:16
  focusing on what's most important to focusing on what
• 25:19
  has the highest probability of success and ultimately what
• 25:22
  delivers the most most value for, you know, for for patients.
• 25:27
  And, and I think that that's the strategy that we've taken.
• 25:29
  And you know, if you imagine a company that's gone from, you
• 25:32
  know 18 potentially 18 programs down to you know, to two
• 25:37
  clinical stage and then a couple that are are preclinical.
• 25:40
  We've represented that that focus that I think the capital
• 25:44
  markets have required over over the last few years.
• 25:47
  But you know what, we're, we're really excited about the impact
• 25:50
  that we, we can have on diseases like Friedrich's ataxia.
• 25:53
  I mean, it's really exciting, you know, even to get one drug
• 25:56
  through an approval, it's, it's a long journey, but it's an
• 25:59
  exciting 1. And ultimately to get there and
• 26:01
  especially in a disease like Friedrich's ataxia, it would be
• 26:04
  a, you know, a great accomplishment for Lexio to, to
• 26:07
  get there in the next couple of years.
• 26:08
  And we're excited. We're excited that we're on that
• 26:10
  path. Very good.
• 26:12
  And what are the next major milestones for Lexio?
• 26:15
  Are there any particular clinical or corporate
• 26:17
  development, corporate developments on the horizon that
• 26:20
  you're particularly excited about?
• 26:23
  Yeah. So as I mentioned earlier, we
• 26:25
  have a data readout for our PKP 2 rhythmogenic cardiomyopathy
• 26:29
  program. We have a number of patients
• 26:31
  that have been treated in our phase one study.
• 26:33
  So I think this will be the, you know, the the first, you know,
• 26:36
  more comprehensive readout of clinical data for for us for
• 26:40
  this program, but also just across the rhythmogenic
• 26:42
  cardiomyopathy field. I think it'll give a good sense
• 26:44
  of, you know, the, the ability to treat this disease with the
• 26:47
  gene therapy and, and then ultimately the degree of impact
• 26:50
  that the therapy can have and, and ultimately as well the
• 26:54
  pathway for this therapy into its, its next study and
• 26:57
  hopefully towards an approval or an accelerated approval.
• 27:02
  We expect to have a data readout, the final data readout
• 27:05
  from our Phase 1-2 study for Friedrich's ataxia in in in
• 27:09
  2026. We're starting the registration
• 27:13
  or accelerated approval study for the Friedrichs and taxi
• 27:17
  program shortly. This that study will have a data
• 27:21
  readout in, in mid 2027. So I think we have a pretty
• 27:24
  robust calendar of clinical data catalysts upcoming.
• 27:28
  And then, you know, on the other side of that, working towards
• 27:31
  the BL, you know, our first BLA for our Friedrichs a taxi
• 27:35
  program, which you know, would hopefully be late 27 or 2028.
• 27:38
  So that's the path we're on. We're we're, you know, we're
• 27:41
  excited to be, you know, headed down that way from a corporate
• 27:44
  development point of view. We, we have, you know, recently
• 27:48
  financed and this gives us a runway into 2028.
• 27:52
  This gives us a runway beyond the registration study for the
• 27:56
  Friedrichs a taxi program. So I don't necessarily expect,
• 28:00
  you know, much on the financing or corporate development front
• 28:03
  in the near term given, given we just completed a raise that we
• 28:07
  really were just focused on executing and and ensuring we're
• 28:09
  delivering, you know, these therapies for patients.
• 28:13
  Yeah. And as ACEO, how do you think
• 28:15
  about building and sustaining a strong company culture?
• 28:18
  Like are there any particular leadership values that are most
• 28:21
  important to you? And how do you how do they shape
• 28:24
  the way that Lexia operates and grows?
• 28:26
  Yeah. So I think the the 1st is we
• 28:29
  have a team at Lexio that's very passionate about patients and,
• 28:33
  and, and in large part very passionate about treating some
• 28:38
  of the rare diseases that that we're focused on.
• 28:40
  And I think, you know, there's a good portion of the team that,
• 28:43
  for example, previously worked in the rare disease unit at, at
• 28:47
  Pfizer and now they're here at Lexio working on rare diseases.
• 28:51
  So you can see, you know, a lot of them have, you know,
• 28:53
  dedicated a good portion of their lives to, you know,
• 28:57
  developing or, or commercializing therapies for,
• 29:01
  you know, for rare disease patients.
• 29:02
  So I think that that passion for treating diseases of this
• 29:05
  profile is something that's important to, to the culture of
• 29:09
  the company. And I think, you know, as a
• 29:11
  company, we've made a lot of progress over, you know, 5 or 6
• 29:15
  years. And I think that's a function of
• 29:17
  just, you know, having, having bold ambitions for, for where
• 29:20
  we're going and, and how we can get there.
• 29:22
  And, and the, you know, the, the timelines that we would take or,
• 29:26
  you know, we don't take any foregone conclusions or
• 29:30
  assumptions about what's possible.
• 29:31
  We try to, you know, focus on, on and be creative as into ways
• 29:36
  to get these therapies of patients faster, to do things
• 29:39
  more efficiently. And I think that that level of,
• 29:43
  we call it operational innovation is important to the
• 29:46
  culture of Lexio and what, what's allowed us to, you know,
• 29:49
  in effectively five years go from a Friedrichs Ataxi study
• 29:53
  that was in, you know, in mirroring studies or in studies
• 29:56
  in mice to one that's now in a registration study.
• 29:59
  So I think that that bold thinking that, you know, the
• 30:01
  pace of, of how we work is important to the, to the culture
• 30:05
  of Lexio, but it also, you know, ultimately allows us to deliver
• 30:09
  treatments for patients faster. And I think that's, you know, in
• 30:13
  my view, is exactly what a patient society should want from
• 30:17
  the biotechnology industry. You know, we're, we're
• 30:19
  unconstrained by red tape. We're unconstrained by, you
• 30:23
  know, large corporate infrastructure.
• 30:25
  I mean, this is the, the, the value of what biotech can
• 30:27
  deliver as small, nimble organizations.
• 30:30
  And I think, you know, Lexio embodies that culture, Bold
• 30:32
  thinking, a rapid pace. We have an undeterred culture.
• 30:36
  If we experience setbacks, we try to find ways around them.
• 30:39
  So that's the culture of Lexio. That's that's, that's helped us
• 30:42
  to get to where, you know, to where we are today.
• 30:45
  Nice. And this is a question that we
• 30:47
  always finish with on the Bio Hub.
• 30:48
  And I know I wanted to give you a bit of a heads up on this one,
• 30:51
  but if you were to have dinner with three people past or
• 30:54
  present, who would they be and why?
• 30:56
  They don't necessarily need to be biotech innovators, although
• 30:59
  they can be if you like. But yeah, three people for for
• 31:02
  dinner. You know, 1-1 would be, you
• 31:08
  know, one would be Martin Luther King.
• 31:10
  I, I think he led a social movement that changed social and
• 31:15
  political movement that changed the, the United States and, and
• 31:19
  frankly may have changed other countries.
• 31:22
  And the, you know, the, the sort of degree of, of leadership and
• 31:26
  thoughtfulness and the manner in which he executed that I think
• 31:29
  was, you know, just very impressive, obviously impactful
• 31:32
  for me as an African American person.
• 31:33
  So that's someone that I would, that I, that I would, you know,
• 31:38
  like to, you know, have dinner with.
• 31:41
  I, I think another is, and this is probably an interesting one,
• 31:45
  but is, is Vladimir Putin, who's living today.
• 31:49
  I, you know, spent time as part of my prior work in, in Eastern
• 31:54
  Europe. I, I, you know, spent time
• 31:56
  living in, in Ukraine actually. And so I, you know, learned a
• 31:59
  lot about the culture in, in that region.
• 32:03
  I, I, you know, I, I, I believe President Putin has designs,
• 32:10
  ambitions for what he believes that the Eastern Europe region
• 32:14
  or maybe Europe should, should look like or should be
• 32:16
  structured as. I mean, it would be just great
• 32:17
  for me to better understand his sort of geopolitical philosophy
• 32:21
  and, and thinking around how he believes the, you know, broader
• 32:26
  world order and Eastern Europe, maybe Europe itself should
• 32:30
  should be structured. And, you know, maybe out of that
• 32:32
  conversation is some thoughts about resolution to the, the
• 32:35
  conflict that, that, that we're seeing there.
• 32:38
  And, you know, lastly, I, you know, a, you know, in terms of a
• 32:46
  business leader, I have, have read a lot of the, you know,
• 32:50
  kind of former Jack Welch books and his leadership style, the
• 32:55
  organization he was able to build the, you know, you see a,
• 32:59
  a, a lot of CEOs that have come out of the GE general
• 33:03
  management, sort of the HR system that Jack Welch built.
• 33:09
  And so there, there's really is something to that type of
• 33:12
  leadership and, and what he's been able to do and sort of that
• 33:15
  legacy that he's left across, you know, many industries and
• 33:19
  from, from his work at, at General Electric.
• 33:21
  So I think that's the, the range of, of individuals that you
• 33:25
  know, I would, I would, you know, be interested to, to, to
• 33:29
  have dinner with and learn, learn from.
• 33:31
  Yeah, I'm sure that'd be a super interesting dinner party for
• 33:34
  sure. So, yeah, look, thanks so much
• 33:38
  for helping us out with this, Lexio.
• 33:40
  I think you've just given a really unique viewpoint of the
• 33:43
  company, the pipeline and all of that, and certainly what I'm
• 33:46
  going to keep be following for sure in the future.
• 33:48
  So yeah, Nolan, thanks again for helping us out with this all.
• 33:52
  Right. Thank you so much.
• 33:52
  Thanks for having me. I appreciate it.