Latest / The BioHub - by Avetix / Episode 164 - Natalia Misciattelli - CEO of AAVantgarde

Transcript

Episode 164 - Natalia Misciattelli - CEO of AAVantgarde · The BioHub - by Avetix

• 0:00
  So we're here in a very nice sunny Bloomsbury Square just
• 0:03
  outside Victoria House. I'm about to go in and visit the
• 0:06
  guys at avant-garde for an episode of the Biohub podcast.
• 0:09
  The guys are developing a gene therapy platform for Star Guard
• 0:13
  disease and Usher 1B syndrome. We're going to meet Natalia,
• 0:17
  who's the CEO. Natalia, thanks for jumping on
• 0:26
  the podcast. Pleasure to have you.
• 0:28
  Thank you very much for having me.
• 0:30
  Great. Good.
• 0:32
  I want to start off with ideally just a little bit of a insight
• 0:35
  or background to your own journey through biotech because
• 0:39
  you've maybe taken a little bit of a unusual route to where you
• 0:43
  are today. Yeah, absolutely.
• 0:46
  So, so I'm a scientist by heart. I'm a trained scientist, PhD
• 0:50
  scientist and and I sort of came into biotech having spent a long
• 0:55
  time in, in consulting in pharmaceuticals and about nine
• 1:00
  years ago made the plunge and and joined the biotech brigade
• 1:06
  and have a look back. Yeah.
• 1:08
  And how did the opportunity with avant-garde come around?
• 1:12
  Like, what's the story there? So with with avant-garde, we're
• 1:16
  a gene therapy company. That's our technology and it's
• 1:21
  my second gene therapy company. So I joined a systemic gene
• 1:25
  therapy company 1st and based on that expertise, when this
• 1:31
  company was formed, I was tapped on the shoulder as in would you
• 1:35
  have a look at this and would this be interesting?
• 1:37
  And I looked at the science and I thought, this is amazing
• 1:40
  science and a great founder, great publications, really
• 1:48
  solids and and I knew that I could build a company around it.
• 1:52
  Nice. And tell us a little bit more
• 1:54
  about that founder and and that science cause original
• 1:57
  technologies from Napoli. That's right.
• 1:59
  Yeah, that's right. So, yeah, so a little bit
• 2:02
  unusual, especially sort of from a global context, but actually
• 2:06
  from an Italian point of view, not so unusual because in Italy
• 2:11
  there's a, there's a large charity called Teleton.
• 2:14
  And, and Teleton is a very well known and very respected charity
• 2:18
  in Italy that's been that was set up by the Anieli family and
• 2:23
  has focused on rare disease for for a long time and have been
• 2:26
  extremely successful in, in not just thinking about sort of rare
• 2:33
  disease, but but really making scientific discoveries, pushing
• 2:36
  things forward, also translating that science into clinical
• 2:39
  programs. And actually, I think last year
• 2:44
  they made headlines because they got the first BLA approved for a
• 2:47
  charity anywhere in the world in the US, which is pretty
• 2:50
  exciting. And I think that goes to show
• 2:53
  the the depth of that organization and our scientists.
• 2:58
  Alberto Riccio is the director of one of their two institutes
• 3:03
  in Italy. They've got one in Milan and one
• 3:05
  in in Naples. And he's the director of the
• 3:09
  institute in Naples. And that's where the science
• 3:12
  originates from. Nice.
• 3:13
  Yeah, I think. Are they the only charity of
• 3:17
  it's got a approved gene therapy or general biologic anything?
• 3:22
  OK nice. Quite some going for.
• 3:25
  Yeah. I mean, it's, it was a huge,
• 3:27
  huge news because of course it's an enormous lift to do that.
• 3:31
  Yeah, yeah. And actually, they're going to
• 3:33
  be marketing the product too. Yeah, yeah, it's pretty
• 3:37
  impressive, right. I mean, yeah, biotech struggle
• 3:40
  to do it. So for a charity to to have that
• 3:42
  capacity is, is pretty incredible.
• 3:44
  Where, where did you come in? Were you involved in sort of the
• 3:47
  seed stage at a company or? Yeah.
• 3:50
  Yeah, yeah. So yeah, when I joined the
• 3:53
  company, we had a wonderful project manager who's still with
• 3:57
  us and the founder as a part time CSO and a consultant CMO
• 4:05
  and then myself. So we raised the the series.
• 4:10
  So I've helped raise the Series A and the Series B and have been
• 4:14
  there from from the beginning. But I should say credit where
• 4:17
  credit's due that we were quite far in terms of the technology
• 4:21
  because Teleton and Alberto had been very successful in getting
• 4:27
  grant funding. So they were two programs that
• 4:32
  were already quite well developed and the platform
• 4:36
  technology, Alberto had worked on that for for decades and had
• 4:40
  really come up with the concept of figuring out how to how to
• 4:47
  enable oversized genes in an AV context.
• 4:54
  And that's really where that's the foundational science.
• 4:58
  And yeah, and, and that's, you know, so we've got two different
• 5:02
  flavours of that science. But sort of from a invention
• 5:05
  perspective, he had the foresight of, you know, this is
• 5:09
  sort of the first generation of gene therapies pursue the the
• 5:13
  size that you can. But he was already thinking
• 5:17
  several steps ahead and thinking, well, if we could only
• 5:20
  pursue some of these other indications where the gene is
• 5:23
  too large, let's figure out how to do that.
• 5:25
  And, and he figured figured that out not just one way, but
• 5:28
  actually two different ways. So it was pretty cool.
• 5:31
  Yeah, I was doing some a little bit of background on Alberta and
• 5:34
  I think, yeah, like understatements, a pretty
• 5:37
  impressive guy. The amount of publications he's
• 5:41
  put out is is, yeah, crazy and real pioneer in the field.
• 5:45
  Absolutely. So obviously we're sat here
• 5:47
  today in London HQ. Is Milan still or?
• 5:53
  HQ is Italy, let's. Put it that way.
• 5:55
  Yeah, yeah, yeah. So we've got, we've got a lot of
• 5:59
  our Discovery team is still in Naples and we've got, we've got
• 6:02
  people in Rome as well and, and then a team here in London, in
• 6:08
  Basel and in the US, yeah. Nice, very good and I know
• 6:13
  obviously talking about the season series AI remember being
• 6:17
  in Vienna, you know during last year's by your actual buyer, not
• 6:22
  by your spring. And I think, yeah, you know, it
• 6:26
  had been a pretty tough funding landscape for for several months
• 6:30
  up until that points when the news on the Series B came
• 6:33
  through. It was a bit like, oh, yeah,
• 6:35
  wow, fair enough. You know, that's pretty
• 6:37
  impressive. You've had investors along for
• 6:41
  the entire journey, though, right?
• 6:43
  You've you've brought a lot of the original syndicate with you.
• 6:46
  Yeah, absolutely. The so the the Series B, of
• 6:50
  course, the the Series A investors were very supportive
• 6:56
  and and that they're very thoughtful investors, very
• 6:59
  knowledgeable is in phobia and Sophie, Nova Atlas, Longwood,
• 7:05
  they've been great not just in terms of financials, but also
• 7:10
  from our expertise perspective. And and the series B we we
• 7:15
  enlarge the syndicates with with more investors.
• 7:18
  It was Co led by Schroeder's and yeah, it was I mean, gene
• 7:25
  therapy is, you know, is an expensive business.
• 7:28
  So, so it was, it was great to be able to, to close the rounds
• 7:34
  in what was a difficult financial climates.
• 7:38
  But I think it come, it shows it's the, it's the data, it's
• 7:42
  still, it's a science and and also it's the team.
• 7:46
  You know, we have an excellent team, not just our founder, but
• 7:49
  the rest of of the team has been fantastic at delivery and and
• 7:54
  being very, very thoughtful as we've been driving the
• 7:57
  programmes forward. Yeah.
• 7:59
  I mean, it's a pretty much a who's who of, yeah, pretty
• 8:03
  impressive investor list for sure.
• 8:05
  And let's get into the platform a little bit and what they're
• 8:10
  sort of backing and the data, because there's two platforms
• 8:14
  that Alberto discovered and touched on and each programme is
• 8:19
  utilizing each platform basically.
• 8:23
  Do you want to give us a little bit more detail on that?
• 8:25
  Yeah, I think you can sort of argue whether it's one platform
• 8:28
  or two, right? I think of it as one platform
• 8:31
  with two different flanges. Yeah, OK.
• 8:34
  Because really what they are, they're dual AV platforms.
• 8:37
  We're utilizing always 2 or we could in theory use 3A VS and
• 8:44
  then we either to enable the the full length gene and then
• 8:49
  ultimately the protein. We're then either splicing at
• 8:53
  the DNA level or at the protein level.
• 8:55
  But it sort of gets us to the same result, which is the end
• 8:58
  product and what we're always trying to do.
• 9:00
  And that's why to me, I see it as as as one platform we will
• 9:04
  always look at driving the best possible efficiency.
• 9:09
  And for ushers that happened or 1B, it happened to be the DNA
• 9:14
  splicing platform. And it's actually the same
• 9:17
  platform that's also used by a course for their auto program.
• 9:22
  And for for star guards, it happened to be the the in team
• 9:27
  platform was the most efficient. So we're always driving for, for
• 9:31
  maximum impact and maximum impact for for the patients.
• 9:36
  And that works done in Naples. That work was done in Naples.
• 9:41
  Patent tips done and very thoughtful.
• 9:46
  Very, very thoughtful. Yeah, nice.
• 9:48
  And, and the two programmes, you've obviously got the, the
• 9:51
  Natural History study running alongside that as well.
• 9:56
  You're fully enrolled on the Usher 1B.
• 9:58
  Trial. So yeah, absolutely.
• 10:00
  So for Usher 1B, we did a Natural History study first
• 10:04
  there too, about 53 patients. That was actually done as an
• 10:08
  academic programme and we licensed that.
• 10:13
  And then we've run the Phase 1 two study.
• 10:16
  It's a dose escalation studying three different doses and we
• 10:20
  announced the 13th of January on this day.
• 10:24
  Wasn't a Friday, was it it? Might have been, I'm not sure
• 10:27
  actually we, we announced that, that we'd fully enrolled the
• 10:32
  program, which was great because now of course we're waiting for
• 10:35
  the data set to mature. It's an open label study.
• 10:37
  So we have been having peaks and, and we have also been
• 10:41
  sharing the, the data with the community because this is the
• 10:45
  first time that anybody has taken a dual AV into the retina.
• 10:51
  So we wanted to make sure that, you know, as we are The Pioneers
• 10:54
  in this space that we share this this data because we are very
• 10:58
  scientifically rigorous team and we wanted to make sure that that
• 11:02
  that data set was out there. So yeah.
• 11:06
  Nice. And and with that full
• 11:08
  enrollment now, is that a case where you've designed the trial
• 11:12
  to expect some data in the next sort of year or so or yeah,
• 11:16
  what's things looking like there?
• 11:18
  Yeah. So we're expecting to have more
• 11:21
  data and to talk more about the data set in the second-half of
• 11:25
  of this year. Yeah.
• 11:26
  Nice. And then for Starguards,
• 11:29
  whereabouts are you up with with that program?
• 11:31
  Yeah. So for Starguards, that's our
• 11:32
  second program. And I think what's very clear
• 11:35
  and I think we always see it that a second program you can,
• 11:39
  you can normally there are synergies between the two
• 11:42
  programmes, that's for sure. And actually we're using a lot
• 11:45
  of the same elements. We're using AV8 for both of
• 11:47
  them. We're using subrational
• 11:48
  injection for all of them. And what we also did was we also
• 11:53
  started a Natural History study for star guards as well.
• 11:56
  There was a Natural History study that existed called
• 11:59
  Procstar. But that study which was
• 12:04
  pioneering and wonderful to understand the the science and
• 12:09
  and also the progression of disease.
• 12:12
  It was done academically and so multiple different centres for
• 12:16
  quite a long period of time, different instruments, things
• 12:20
  changed. And so the the rigor of of
• 12:26
  running a study that you're doing internally over a shorter
• 12:29
  period of time has given us a, a different data set that will
• 12:35
  help us for the future too. So our Natural History study is
• 12:38
  fully enrolled. Nice.
• 12:39
  It's 150 patients. OK.
• 12:42
  And then we are in the middle of our of our Phase 1 two study for
• 12:46
  star guards. Yeah.
• 12:47
  OK. Makes sense.
• 12:48
  And how have you designed the study in terms of endpoints?
• 12:51
  I know that was a discussion you had earlier this week on the
• 12:54
  panel with the guys at Bio Europe.
• 12:56
  Have you looked to fairly novel endpoints?
• 12:59
  Are they pretty traditional? I mean, it's a Phase 1 two
• 13:02
  study. So we're, we're looking at all
• 13:04
  the endpoints that you would imagine and, and we will see
• 13:08
  what, what we decide for, for the future.
• 13:11
  What we've learned from from ushers is it's important also to
• 13:15
  capture the the patient reported outcomes, especially when we
• 13:21
  know that for some, for some diseases, it's harder to, to get
• 13:26
  to a functional endpoint. For ushers.
• 13:30
  We've published data showing BCVA, so you know, eye charts
• 13:34
  and, and shown that we're actually seeing improvement in
• 13:37
  the first patients, which is very exciting.
• 13:39
  And for for star guards, we're making sure that we've got all
• 13:43
  the same endpoints that we've got for for ushers.
• 13:46
  But in terms of the ranking, that remains to be seen.
• 13:51
  Yeah, fair, Nice. And then in terms of, I know
• 13:54
  there's an area that gene and cell therapy to be fair has, but
• 13:58
  they struggled with over the years in terms of
• 13:59
  manufacturability. I know you're in obviously quite
• 14:02
  a lot of patience open to be. How are you finding that, you
• 14:06
  know, pretty well set technology now?
• 14:11
  I assume the team are doing a good job on that front.
• 14:13
  Like how do you plan for that to scale up process, you know, not
• 14:17
  necessarily right now, but but later on?
• 14:19
  So we have an amazing team. I have to say that CMC is is a
• 14:24
  stronger, is an area where you really need to have expertise.
• 14:27
  If you've got a strong team, you can really excel.
• 14:29
  And we have an amazingly strong team.
• 14:32
  They've been around gene and cell therapy for decades.
• 14:36
  They've been pioneers, they're rigorous, they know what to do.
• 14:41
  But we also have got the advantage that it's the eye.
• 14:44
  So we need relatively small quantities, but of course we
• 14:48
  need high quality quantities. And and I have to say that kudos
• 14:55
  where kudos is due that our CMC team has has never actually
• 14:59
  failed a single batch. Yeah, that's, that's good.
• 15:03
  I know it's obviously been in the news with, with Ham Gen.
• 15:05
  X, right and the the issues there recently.
• 15:07
  But I, I get that the eye as an organ as it were is a yeah,
• 15:12
  slightly different kettle of fish for sure.
• 15:15
  Nice. And then just generally looking
• 15:17
  ahead for the next sort of year, 18 months, what can we expect
• 15:21
  from you guys clinically, like commercially just business wise
• 15:26
  in terms of updates? You can expect a lot from us.
• 15:31
  We've got two programs in the clinic, so they will and they're
• 15:34
  open label studies, so they will.
• 15:35
  We will be publishing, we will be sharing information, we'll be
• 15:39
  sharing news and we've got a lot of exciting progress that that
• 15:45
  we'll be sharing with the community.
• 15:48
  For us, the inheritor retinal disease community has been
• 15:52
  historically underserved. They've got, there are very few
• 15:54
  treatments. So we're excited about
• 15:57
  supporting the community and and we're excited about sharing our
• 16:01
  data when it matures. Nice.
• 16:03
  And in the long run, I guess that's probably what you'd say
• 16:05
  if you were looking back in five years from now in terms of the
• 16:09
  impact that you guys have had, that would be the main point for
• 16:12
  you, I guess. Oh, absolutely.
• 16:14
  Absolutely. I think in the end, this is all
• 16:17
  about getting products that are meaningful to patients that need
• 16:22
  them. And we know that both of these
• 16:26
  diseases are debilitating. These are diseases of young
• 16:30
  people. So if we can help these people
• 16:35
  change their opportunities, provide independence, provide
• 16:40
  hope, that is tremendous. And I think even at this point
• 16:44
  in time, we, we hope, we're bringing hope to the patient
• 16:49
  community that we will be helping them.
• 16:52
  Yeah, I guess it must be really rewarding to, yeah, see initial
• 16:56
  data coming in from from any patient even in the phase one to
• 16:59
  study. And like you say, it's these
• 17:02
  indications, they're like, not to downplay losing sight as you
• 17:05
  get older. It's it sucks, obviously, but
• 17:08
  yeah, these are really young people who have got their full
• 17:10
  lives ahead of them otherwise. So yeah, cool.
• 17:14
  Very good. And I think for the for the
• 17:16
  ushers patients especially those patients are born deaf, they've
• 17:20
  got balance issues and then they go blind.
• 17:24
  So I think especially for that patient population, it's an
• 17:28
  opportunity to help them with the the site.
• 17:31
  But of course, there's also a possibility in the future to
• 17:34
  help them with other elements of, of their disease and that's
• 17:37
  also exciting. So we really, we're, we're
• 17:41
  committed to the community and we're committed to making a
• 17:43
  difference and leveraging our technology.
• 17:46
  Yeah, awesome. Well, best of luck with
• 17:48
  everything and yeah, looking forward to seeing the progress
• 17:51
  as the as the year goes on. Thank you very much and awesome.
• 17:54
  Thanks for the questions. Yeah.
• 17:55
  Thank you.