Latest / The BioHub - by Avetix / Episode 216 - Tom Ciulla - CEO Ikarovec

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Episode 216 - Tom Ciulla - CEO Ikarovec · The BioHub - by Avetix

• 0:06
  So today on the Buyer Hub, I'm joined by Tom Ciulla, CEO at
• 0:09
  Caravec. Tom, welcome to the podcast,
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  first and foremost. Callum, thank you very much for
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  having me today. Oh, absolute pleasure.
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  We're going to get into the Caravec story a little bit later
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  on, but for those of, you know, listening who who haven't heard
• 0:27
  of it, Caravec, we're going to set the scene.
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  And I think just as maybe start things off, people may have
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  heard of yourself within the ophthalmology space, Tom, for
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  sure, given the track record, I want to go back a little bit and
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  just set the scene. Obviously you've had some major
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  achievements in the space because of free FDA approved
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  drugs in a variety of different indications.
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  Part of the Spark team led the 1st in vivo gene therapy
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  programme that was approved by the FDA like Sterner, obviously
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  more recently with Viridian. How is that sort of learning and
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  that development shaped you as a person and and how you're taking
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  things into a Caravac well? I, I guess I should first start
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  by some of my, my background. So I'm a, I'm a Harvard trained
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  board certified ophthalmologist and retina specialist.
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  I've been working on in in retinal diseases for 30 years
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  now. Originally had a traditional
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  academic job with a research lab, different models of
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  angiogenesis. Then got involved in all the
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  clinical trials with the drugs that many of you have heard
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  about starting with Visodyne, then Macogen, Lucentis, Eylea,
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  Ozurdex, etcetera. And that was really fun.
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  And then ultimately after about 20 years of doing that, went
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  back and got an MBA, started working in industry.
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  I worked in four publicly traded biotech companies prior to a
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  Caravac. I was Chief Medical Officer at
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  the last two and I've worked on now 4 drugs that have been FDA
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  approved, including Iservay, which is one of the two approved
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  therapies for geographic atrophy, our target indication.
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  And also worked on Luxterna, which as many of you know is the
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  first FDA approved gene therapy for hereditary disease.
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  And it's been a, it's been an incredible journey.
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  When I was in my training, I never thought I would witness so
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  much innovation. It's, it's just been an amazing
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  amount of innovation. In fact, in my training at NASAI
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  near Harvard, we were trained to actually laser a patient's fovea
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  if they came in with wet AMD. We would tell these patients
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  that we would create a blind spot in their vision, in the
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  central vision that would be smaller than the blind spot that
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  nature would ultimately create from their wet AMD.
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  And since then, it's just been a remarkable journey with, with
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  anti digests that have helped millions of patients.
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  Then I never thought I would see gene therapy in this space where
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  we, we, we with Luxterna, we're able to administer this therapy
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  to, to children essentially born blind and be for them to be able
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  to then go trick or treating for the first time or to play catch
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  with their dads for the first time.
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  It's just been an incredible amount of innovation on this
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  journey. Yeah, massively.
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  I, I've sold you short there as well.
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  Sorry, 25% short, I missed one approval off.
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  So yeah, I sold you down the river.
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  Nice. And you've done that all the
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  while while still practising, still seeing patients as well.
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  Do you want to just touch on that briefly, because I guess it
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  must give you such a sense of perspective, I guess in the
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  main, right? Well, that's absolutely right.
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  So I, I practice on a very limited part time basis now, but
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  I still practice mostly on Friday afternoons when I'm, when
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  I'm, I'm, when I'm not traveling.
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  And it's absolutely true to, to have this perspective.
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  I still see patients with geographic atrophy, for example,
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  and many of them don't opt for current treatment because of the
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  treatment burden as well as the the limited functional benefit.
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  And so to be able to witness that first hand, it really gives
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  me a sense of the unmet need and that's what we're trying to
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  solve at a Caravec. Yeah, nice, very good.
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  Well, I guess that brings us nicely into a Caravec.
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  Look, we've obviously touched on your track record.
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  It must have been something super interesting, super
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  exciting to pull you into the business and talk to us a bit
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  more about how you got into contact.
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  Yeah, one thing led to another how it came about.
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  Yes. Well, as I mentioned, I worked
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  in four publicly traded biotech companies prior to a Caravac and
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  I was contacted by a, a, a recruiter and it really
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  intrigued me to, to try to take a preclinical gene therapy
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  company into the clinic and, and background.
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  Having been a clinician and a clinical trialist and then
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  working in industry, I felt that it was a, a position that was
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  well suited for this point in my career.
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  And I, I think the exciting part is the science is what drew me
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  into a Caravac. Katie Binley, who's been working
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  on gene therapy for 25 years, and the rest of the team have
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  really built an amazing scientific platform with
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  bicystronic or bifunctional gene therapy.
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  So what the platform based involves is making two
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  therapeutic proteins with 1 gene therapy vector and the proteins
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  are designed to be synergistic. So for our first asset which
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  focuses on geographic atrophy, we're taking a validated pathway
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  complement modulation and adding to that neuroprotection with
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  with pigment epithelial Dr. factor.
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  And by adding the neuroprotection, we think that
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  we can potentially create functional benefit that the
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  current therapies have in very limited ways.
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  And I so that science really intrigues me and there's a lot
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  of support for this in the literature as well as support
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  for this in the company's preclinical studies.
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  And what's really exciting at ARVO this year, Arvo's our
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  largest ophthalmology research meeting in the world.
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  At ARVO this year there was a group that actually looked at
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  PEDF gene therapy in patients with retinitis pigmentosa and
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  what they found was a functional benefit when they compared the
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  treated eye to the fellow eye. And again, this is in retinitis
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  pigmentosa, but nevertheless A retinal degenerative disease.
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  So we now have for the first time clinical validation of this
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  approach. So I, I think the science was
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  most compelling. And then also the, the team, as
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  I mentioned, Katie Binley, our Chief Scientific officers has
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  been doing this for a long time and they really built up a, a, a
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  really nice scientific platform with a very credible team.
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  Another member of the team, Andy Osborne, who's a Vice President
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  of Preclinical Research worked at our predecessor company
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  Quathira on bisysphonic gene therapy and that was acquired by
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  Estelas a few years ago. And so this team has a lot of
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  experience in bio systronic gene therapy.
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  And then finally, I think the opportunity to be able to take
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  on a, a, a company currently preclinical and, and really try
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  to, you know, mold it so that it becomes a, a viable clinical
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  company. Yeah, for sure.
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  And I guess it's not the most usual place even in the UK to to
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  find a biotech. Obviously the guys are out in
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  Norwich, which for anyone listening who doesn't know where
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  Norwich is, it's stuck out on the eastern side of the, well,
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  England. It's, it's quite difficult to
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  get to. It's not in the Golden Triangle.
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  It's really amazing what the group have pulled together
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  there. I know obviously Katie's over in
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  Oxford, but yeah, it's, yeah, an amazing little hub that you have
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  there for sure. Yeah, it turns out to be a
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  really great place for our company, Norwich Research Park.
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  It it's really sort of an incubator area for biotech
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  companies. Most of the biotech companies,
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  they are working on plant biology.
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  So we're unique, they're working on human gene therapy.
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  But nevertheless it gives us access to wide swath facilities
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  that we wouldn't otherwise have access to.
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  And also it's a very cost effective a place to have a
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  headquarters. And because it's at at the
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  University of East Anglia, it's also an area that has attracted
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  a lot of, you know, a lot of post docs and, and PhD
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  candidates. We'll often have interns working
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  in our labs. Yeah, nice.
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  It's perfect place as a preclinical bio set to to be
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  really right. So nice.
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  You've obviously touched on the fact that you guys are still
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  preclinical. I know you probably can't won't
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  go into too much detail on on the data that you've you've
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  shared already, but what is the current state of plate on what
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  have you seen that really makes you excited about the approach
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  in in the models that you've run so far?
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  Yeah, absolutely. And this is what as I mentioned
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  earlier what what attracted me to to the company, they were
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  very strong scientific foundation.
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  So our lead asset ICAR 001 which as I mentioned is a bisestronic
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  or or dual function gene therapy combines complement modulation
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  with neuroprotection. And what we've shown in in
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  several preclinical models is that we can preserve the anatomy
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  of the retina as well as the function of the retina and these
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  various models of geographic atrophy.
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  We've also completed a non human primate dose ranging study where
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  we've ascertained doses that we think will be efficacious in
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  humans and we've had some positive interactions with with
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  the FDA who's supportive of our our strategy.
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  And finally, we've developed a scalable suspension based
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  manufacturing process, which for a gene therapy company is a, is
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  a is a big deal. So we're in the process of
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  fundraising and as soon as we have funds we plan to
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  manufacture our clinical batch and start to file our Ind and
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  eventually get into the clinic with the geographic afterpage
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  file. Yeah, it's, I mean it's a super
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  exciting next sort of 12 to 18 months for you guys.
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  We'll get on to the Series A and and the plans for the clinical
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  in a little while, but I wanted to touch on something there.
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  You obviously mentioned that the lead asset is targeted towards
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  geographic atrophy. Given the sort of mode of
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  action, the approach you guys have with the technology, could
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  you bring it into other indications as well?
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  Is that a feasible looking down the road?
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  I know it's something you might not look at initially, but yeah,
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  what are your plans there? Yes, excellent question.
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  I mentioned that you know, at Argo this year we saw the first
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  human clinical data of a PEDF gene therapy and retinitis
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  pigmentosa. So we'll be targeting retinitis
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  pigmentosa as well as a second indication.
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  As many know Luxterna for example targets patients with
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  RPE 65 gene mutations and what the the benefit of our therapy
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  is that it's gene agnostic. So we think this might be able
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  to treat a broad swath of retinitis pigmentosa patients
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  where there's just a huge unmet need.
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  As I mentioned earlier, I still see patients and I still follow
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  some of these retinitis pigmentosa patients who really
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  don't have mutations amenable to current therapies or to
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  therapies that are in development.
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  And so for these patients, having a gene agnostic therapy
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  would be very meaningful. So we'll be looking at retinitis
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  pigmentosa as our second indication.
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  Nice. Cool and great, but it opens up
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  so many patients who, like you say, are without meaningful
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  options right now. Cool.
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  I know you briefly mentioned the Series A before and that's
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  that's still in process as we record this, but how have you
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  found those conversations? And yeah, what what's the sort
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  of investor appetite looking like for the biosistronic
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  approach? Like, you know, what feedback
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  have you had? Well, yeah, great question.
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  This has been a a difficult time for fundraising and and biotech.
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  A lot of investment dollars over the past few years have been
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  going into technology and artificial intelligence.
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  But nevertheless we've had a a lot of progress.
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  We now have a lead investor with a assigned term sheet.
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  Two of our existing venture capital firms plan to invest in
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  our Series A. We've had some follower
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  investors who want to invest and we're still having conversations
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  with additional investors. So we've made a lot of progress
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  in the fundraising side despite the challenging environment.
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  It's it's been an environment that's been especially
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  challenging for preclinical gene therapy companies.
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  But the investors that we've engaged with have seen, you
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  know, our strategy, they understand the strategy and
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  they're very excited about the opportunity.
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  Yeah. I, I was going to ask actually
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  because it is a challenging environment to raise funds and
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  particularly when you don't have existing clinical data.
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  What what's particularly resonating most in those
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  conversations? Is it the platform and the
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  potential indication expansion access to bigger patient
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  populations like is is there any specific or is it a bit of a
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  mixed bag? Well, I think it's a combination
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  of the above. As you know, Cal, this is a huge
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  unmet need for geographic atrophy treatment.
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  Current treatments require patients to come in every month
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  or two indefinitely. So there's an enormous treatment
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  burden and and we we know that complement only approaches have
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  a ceiling of efficacy. So I think, I think the unmet
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  need resonates with investors. I think the differentiation of
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  our of our asset combining neuroprotection with complement
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  modulation resonates with them. I also think the the the team
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  because as you know in in these preclinical companies, the the
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  team, the leadership of the board, they all count for
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  something when investors evaluate the opportunity.
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  Yeah, massively and I mean on that front of the team certainly
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  got stuck in at Arvo, right. You have numerous poster
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  presentations and and whatnot sharing with the the community
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  what what you guys are up to. Obviously, fingers crossed that
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  Series A closes relatively soon and I'm sure we'll see the press
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  release when it does, Tom. But looking ahead, when you have
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  that money in the bank, so to speak, what do the next 12 to 18
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  months look like? You mentioned obviously plans
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  for for a phase one in GA Yeah. How quickly would that come
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  about? Well, we'll, we'll be completing
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  our GLP talk study. We'll be manufacturing a
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  clinical batch and then we plan to initiate a trial in
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  geographic atrophy. We hope to dose the the first
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  patient within a year of funding.
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  And then once we have safety data from the geographic atrophy
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  trial, we also plan to to implement a retinitis pigmentosa
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  trial. So our our timeline is, is
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  essentially to dose the first patient within a a year of
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  funding. Understood.
• 16:06
  Cool, Very good. And then on a final point, just
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  going back to I guess the beginning really and and what
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  excited you the most about joining Acorvac?
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  Yeah, obviously taking a company from preclinical to clinical as
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  CEO, it's obviously your first time as a as ACEO.
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  Tom, how have you found the transition as someone who
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  obviously has a tonne of industry experience across a
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  variety of different companies? But yeah, it's still a different
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  thing, right? You're stepping into that hot
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  seat, as it were. Every decision lands on your
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  desk. Fundraising like we've been
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  talking about how, how have you managed that and and how have
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  you found it? I, I, I found it actually
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  invigorating. I, I, I think coming in as a
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  clinician and clinical researcher with experience in
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  industry, you know, obviously I'm very passionate about this.
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  I feel like I bring a lot of credibility to people and I feel
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  like that, you know, I can explain this to investors from a
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  almost a first person perspective.
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  So that part's been fun to be able to connect the science with
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  the clinical unmet need and the and the opportunity that a
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  Caravec presents as an investment has been actually a
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  lot of fun. You know, obviously the hardest
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  part will be time allocation as we become busier and we'll have
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  to obviously build a team to help with that.
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  But we've had a lot of help with our board.
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  We have an amazing board. Dave Geyer is our board chair
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  and Dave Geyer is probably the best known retina specialist,
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  entrepreneur, biotech executive in the in the space right now.
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  He's had $3 billion plus exits most recently with the sale of
• 17:57
  Ibio and Merck. So he brings a lot of expertise
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  and experience and he's been super helpful.
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  The rest of our board's also very helpful.
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  Jean Felix Cambal is a very well known and seasoned gene therapy
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  executive who brings a lot of expertise, particularly around
• 18:19
  gene therapy, GLP, tox design and manufacturing.
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  And then we have three investment directors who've been
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  very helpful as we work with the other investors and, you know,
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  share the, the story with them. So it's been a, it's been fun.
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  I feel like at this point in my career, to be able to combine my
• 18:42
  clinical background with my industry background and apply it
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  to, you know, helping to develop the company has been really
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  invigorating. Yeah, and I think it's
• 18:54
  interesting that as part of the answer to that question, Tom,
• 18:57
  that you went to credit other people as well on on the board
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  who brought so much. I mean, obviously I know Jean
• 19:04
  Philippe pretty well. He's on the board at Splice and
• 19:06
  Mikel has been on the podcast before, another cool company.
• 19:11
  But yeah, it goes some way to explaining that.
• 19:15
  I guess the saying is that it takes a village right to to get
• 19:18
  this kind of company off the ground and and into a phase one
• 19:22
  where you're actually looking at, you know, how is this going
• 19:24
  to impact patients. But yeah, it's interesting that,
• 19:28
  yeah, you've really focused there on who's helped and who's
• 19:33
  brought it all up together rather than just focusing on on
• 19:36
  your own shift in approach. That's yeah, I think that says
• 19:40
  something about how how modest you are as well in in terms of
• 19:43
  your own track record and yeah, what you're contributing to the
• 19:46
  team. But, and I know, yeah, but yeah,
• 19:52
  look fantastic to have you on. Really enjoyed the conversation.
• 19:55
  And more importantly, really looking forward to seeing how
• 20:00
  you guys progress over the next, Yeah, 12 to 18 months.
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  It's an exciting time. And yeah, we'll stay in touch.
• 20:08
  Calum, thank you so much for having me on.
• 20:10
  It's been a real pleasure speaking with you today.
• 20:14
  Thanks, Tom.