Latest / The BioHub - by Avetix / Episode 229 - Frederic Marrache - CEO of Bionyra

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Episode 229 - Frederic Marrache - CEO of Bionyra · The BioHub - by Avetix

• 0:06
  So Frederick, great to have you on the Essex Bio podcast.
• 0:09
  Thanks for coming on. Thank you very much for having
• 0:11
  me. Pleasure being here.
• 0:13
  I'm looking forward to this question.
• 0:15
  Absolute pleasure. I mean, we'll we'll get into the
• 0:18
  Bionera story a little bit, but I guess to start things off,
• 0:23
  Frederick, I think it's always useful to yeah, give some
• 0:26
  context to give us a history lesson on on your own journey
• 0:29
  through biotech. And I think the thing that I was
• 0:32
  most curious about and perhaps our audience as well is yes,
• 0:37
  sort of what needed to happen or what stars or planets needed to
• 0:41
  align for you to move from, you know, a decade long role, Sanofi
• 0:48
  or career, It's an office through different roles into Co
• 0:51
  founding a seed stage biotech at that stage 'cause they're two
• 0:55
  very different worlds. But yeah, I'll, I'll let you
• 0:58
  explain some more. Sure, sure.
• 1:00
  I'm happy to do so. I mean, it's, it's been quite a
• 1:04
  journey and I think for me it's always been about eventually
• 1:09
  building and and creating a new company.
• 1:12
  I always had this entrepreneurial each, it's been
• 1:17
  a bit my story. I, I never quite knew exactly
• 1:21
  how to go about it, right, Because you always have, you
• 1:25
  know, you have very different ways to become an entrepreneur.
• 1:29
  You can be the inventor, you can be more of a business founder,
• 1:34
  you can be an investor. I mean, there's so many angers
• 1:36
  to that. And it took me a while to find
• 1:39
  my own story. And maybe I should go back and
• 1:43
  tell you a bit more about my background beyond the last 10
• 1:46
  years with Tanofi. I mean, I initially trained as
• 1:49
  an MD, PhD in France. I trained as a
• 1:51
  gastroenterologist. I moved to the US and did my
• 1:58
  post doc at Columbia University in the same field.
• 2:01
  At the time, my aspiration was to pursue an academic career,
• 2:07
  but I had a realisation that maybe it was not for me.
• 2:14
  Maybe I wanted to have a different career.
• 2:17
  I wanted to have different experience to go through
• 2:21
  different, I'd say journeys with the idea that at some point I'd
• 2:26
  like to create my own thing. So I didn't really know what to
• 2:28
  do. I did an MBA at the time.
• 2:30
  I worked in management consulting with McKinsey for
• 2:34
  several years before eventually going back to the life science
• 2:38
  sector and joining Sanofi, where I spent all my time within the
• 2:45
  R&D organization and more prominently in the immunology
• 2:52
  and inflammation clinical development franchise, which was
• 2:56
  built around Dupixent. And I've been very lucky and
• 3:00
  fortunate to join such a franchise and to see the
• 3:03
  emergence of what is I believe now probably the biggest drug in
• 3:10
  the immunology and inflammation space.
• 3:13
  It's it's a massive mega, mega blockbuster, I don't know how
• 3:17
  you call it. So this is a little bit the
• 3:20
  journey that led me here today. As I said, always wanted to
• 3:23
  experience and do different things.
• 3:25
  Had this entrepreneur entrepreneurial each and working
• 3:29
  several years in the big pharma. Also appreciated that there's
• 3:34
  probably way to do things a bit better by just being faster,
• 3:38
  nimbler and try to look for things that may still be a bit
• 3:43
  under the radar and build the pipeline that would be basically
• 3:48
  turnkey ready for, for for anyone going forward.
• 3:52
  So that's was to me the rationale.
• 3:57
  I also felt that there's a lot of room to improve on the
• 4:00
  current drugs we have. And I felt that now was the
• 4:05
  time. I felt that I really had done a
• 4:08
  lot of clinical development. I knew how to progress a drug
• 4:15
  through the different steps of clinical development.
• 4:17
  I knew I we knew how to go about it and I could bring that in my
• 4:22
  project. Yeah, for sure.
• 4:26
  It's an interesting one. And and you mentioned Dupixent,
• 4:29
  yeah, I guess it's the inspiration behind a lot of
• 4:31
  these sort of next Gen. molecules that we're seeing
• 4:34
  across immunology, not just on on the gastro side.
• 4:37
  But what what was it that like obviously timing aligned there
• 4:42
  was an opportunity and how did it come about with the guys
• 4:46
  because it was stuffing over who obviously let the seed round,
• 4:50
  right. And how, how did those
• 4:52
  interactions take? I I presume it didn't happen
• 4:54
  overnight, Frederick. No, it doesn't.
• 4:57
  It doesn't. And as I said, it's been a a, a
• 5:02
  multi year process and journey to get to this point where I
• 5:06
  was. I felt I was ready and when
• 5:09
  there was a window of opportunity to do something that
• 5:13
  really played into my experience.
• 5:16
  So the story that I knew the Sofi Nova team previously I had
• 5:24
  networked with them as part of the key player in the French
• 5:28
  biotech ecosystem. We discussed project, previous
• 5:34
  project with them that eventually didn't progress and
• 5:40
  eventually this one worked. We felt that you know there is a
• 5:46
  real opportunity these days to build clinical stage companies
• 5:52
  from the get go by building a pipeline of clinical stage
• 5:57
  assets and in licensing them early on and that especially in
• 6:03
  immunology and inflammation there was a lot of
• 6:06
  opportunities. So, so Fenova clearly joined
• 6:11
  force with me. They had a lot of experience in
• 6:13
  company building. They have a a very significant
• 6:16
  outreach that helped us first in licence the assets and identify
• 6:22
  the ones we felt were relevant and could be a a key element of
• 6:29
  our pipeline and 2nd lead the fundraise beyond the the seed.
• 6:36
  Yeah, it's, it's, it's interesting that you mentioned
• 6:39
  just, I guess what's impressive about stuff and oversight is the
• 6:43
  the breadth of options that they seem to assess and and have.
• 6:48
  And, and I know the guys have a the proprietary platform, which
• 6:51
  is essentially like AI guess a big opportunity list of of, you
• 6:56
  know, options that are out there and a lot of tools that help
• 7:00
  them screen those and then select for potentially first or
• 7:03
  best in class efficacy. So, yeah, but you've got to have
• 7:06
  the funding as well to back it up when you see a good idea,
• 7:09
  right. So yeah, makes sense.
• 7:12
  I mean getting onto the assets that you did you know in license
• 7:18
  and and the sort of backbone of the the story behind Bionere.
• 7:22
  And now do you want to give a quick high level on on each and,
• 7:26
  and I guess we can dig into afterwards in a bit more detail
• 7:30
  the two clinical stage assets? Absolutely.
• 7:34
  So I like to say we have two pipeline in our pipeline. 1 is
• 7:40
  our type information which where we have our our anchor molecule
• 7:50
  which is BYN001. It is an entire interleukin 25
• 7:56
  monoclonal antibody that also has half life extension
• 8:02
  features. Interleukin 25 is part of the
• 8:09
  alarming family like TSL, PIA33. It is expressed by epithelial
• 8:16
  cells in response to any aggression or stress.
• 8:21
  And I25 in particular is a key driver of type 2 inflammation,
• 8:25
  which is the key pathway involved in all immunoallergy
• 8:30
  condition. In our case, we focus on atopic
• 8:33
  dermatitis as the first indication, but it's also
• 8:37
  relevant to a number of indications like a drug like
• 8:40
  Dupixent, ES, like asthma, CBD, nasal polyposis and the list is
• 8:47
  quite long. So I'm not going to expand on
• 8:51
  this. I think one of the unique and
• 8:57
  exciting aspect of this molecule is that it's a new MOA and I'm
• 9:02
  really excited about it. I keep saying I see it as the
• 9:05
  most exciting emerging mechanism of action in the field of atomic
• 9:10
  dermatitis. What's really exciting is that
• 9:14
  it comes from the get go with this half life extension
• 9:16
  features. And I'm sure, you know, it's
• 9:17
  been a trend across across pharma to have this improved
• 9:24
  convenience with less frequent administration and as a result,
• 9:28
  very significantly reduced needed burden for patients.
• 9:33
  And now, you know, over the recent years, the, the what was
• 9:38
  causing anxiety is that you have a new MOA, but you know that
• 9:41
  three years down the road there would be someone who would come
• 9:44
  with an improvement over your molecule with this half life
• 9:46
  extension feature. So we have it already, right?
• 9:49
  And now people are also anxious that someone is going to come
• 9:52
  with a multi specific molecule that is going to combine you,
• 9:55
  you lead target with something else and we will also develop
• 10:00
  multi specific down the road. So we're trying to make sure
• 10:02
  that we have the full I-25 toolbox and that we sustain the
• 10:08
  best in class profile. So that's for the type 2
• 10:12
  inflammation slash interleukin 25 French size.
• 10:16
  Then the suborgon piece of the second pipeline, our pipeline,
• 10:19
  the TL1D pipeline and here we have two molecules, we have ATL
• 10:26
  1A mono specific with half life extension and ATL one AI23P19 by
• 10:33
  specific molecule. And I feel they really
• 10:36
  complement them, complement one another very well.
• 10:42
  If you have followed the TL1A field, it's been a bit of a game
• 10:46
  changer story in the INI field and especially in the
• 10:50
  inflammatory bowel disease space.
• 10:54
  It came out now two or three years ago that TL1A happens to
• 10:58
  be a very exciting mechanism of action.
• 11:05
  There were initial results from the first generation of TL1
• 11:09
  antibodies, namely promises and and HOI venturing consistently
• 11:15
  that you had the level of efficacy that seemed probably
• 11:18
  better than any of the mechanism of action that had already been
• 11:22
  approved. And it drove real massive
• 11:26
  enthusiasm with very significant delectivity.
• 11:29
  I'm sure you you know that. So now we have a real
• 11:33
  opportunity to build on that in the inflammatory bowel disease
• 11:36
  space. And our view has been the next
• 11:39
  iteration is going to be about increasing the level of efficacy
• 11:44
  and combining TL1A with something that is going to
• 11:48
  improve the level of efficacy. And as many, we feel that the
• 11:51
  best way to go about it is to leverage proven mechanism.
• 11:55
  And here it's I23P19, which not only is very effective because
• 12:00
  we know the efficacy profile of drug like Scalyzi or Tremfya,
• 12:05
  but also has a very favorable safety profile.
• 12:08
  So you, you, you, you, you're not concerned around cumulative
• 12:11
  toxicity with this combination. So we really feel that this is
• 12:15
  going to be a very exciting play in the IBD space and we have a
• 12:22
  molecule which is a bispecific molecule which is extremely
• 12:25
  potent and which we as a result we believe also be infrequently
• 12:33
  dosed and we represent a very convenient option for patients.
• 12:39
  So that's for one piece of the TL1 is then we still have this
• 12:41
  mono specific molecule and I think some of our competitors
• 12:45
  also have a monospecific molecule with this half life
• 12:49
  extension. But our idea is probably to
• 12:53
  position it a bit differently. I mean we feel we have a very
• 12:56
  competitive molecule. We probably have one of the
• 12:58
  longest half life in this space and hopefully we'll present some
• 13:04
  of the data shortly. We also have a very favourable
• 13:08
  immunogenicity profile and this has been a real concern in this
• 13:12
  case with this class because one of the first generation
• 13:16
  molecule, Tim Kebart from Roche has something like 60 to 80% ADA
• 13:24
  and a lot of people have speculated that that maybe was
• 13:29
  more target related than molecule related.
• 13:32
  So that that's been a concern. We know that we don't have to be
• 13:36
  concerned about that with this molecule, which is great because
• 13:42
  this molecule is also the backbone of our multi specific
• 13:44
  so far as it's the first level of the risking.
• 13:47
  But going back to the mono specific molecule, I'm sure you
• 13:53
  know that in the ionized space it is very rare to see a
• 13:57
  mechanism, mechanism of action that remains limited to single
• 14:01
  indication. And here everyone's been
• 14:05
  assuming that eventually Tier 1A is going to be relevant to other
• 14:09
  indications. Which one in harmony has been
• 14:13
  the question. We're getting now some clarity
• 14:17
  about that, but we still need to learn more.
• 14:22
  And we feel that the opportunity for our drug is probably going
• 14:26
  to be outside of the inflammatory bowel disease space
• 14:28
  because in the IBD space, you are stuck between the first
• 14:32
  generation, the emerging wave of bispecific, which I think makes
• 14:35
  it a bit complicated. We're not ruling it out.
• 14:38
  I think it remains open. So our view of this TL 1 1/2
• 14:43
  life extended drug is that it's sort of your backbone for
• 14:47
  anything in the TL1 space. We're prioritizing for now the
• 14:50
  non IBD space in the TA1S Corp and we have recent results from
• 14:56
  some of our competitors over the sub summer in dermatology with
• 15:00
  hidradenitis suppurativa, in rheumatology with rheumatoid
• 15:04
  arthritis where there is a good efficacy signal.
• 15:07
  Is it sufficient for to develop this drug as monotherapy or will
• 15:13
  when they need to be combined with a partner either through a
• 15:16
  multi specific or through the combination of half life
• 15:19
  extended drug? That is the question everyone is
• 15:21
  asking. I tend to think the latter
• 15:24
  right. You want to go directly to the
• 15:25
  highest level of efficacy, but this remains to be seen.
• 15:31
  I think you still have that option.
• 15:32
  Also in IBD you can combine this mono specific with different MOA
• 15:36
  than IA 23 P 19 and there's going to be probably a number of
• 15:39
  new emerging and exciting MOA that could be combined with TLA
• 15:42
  down the road. So again, I think even if it's a
• 15:46
  motor specific drug, it's all going to be about multi
• 15:49
  targeting and that's what Bioneera is about.
• 15:51
  Bioneera is about really realizing the full potential for
• 15:55
  multi targeted biology, be it with multi specific or
• 15:59
  leveraging the monospecific molecules we have that can be
• 16:01
  combined. There's one very exciting
• 16:05
  opportunity we see going forward with this Tier 1A molecule going
• 16:08
  back to this, it is in atopic dermatitis.
• 16:14
  It is possible that TL1 it could be relevant to atopic
• 16:18
  dermatitis. There is there is an ongoing
• 16:20
  study from one of our competitor and we believe or we expect the
• 16:24
  be doubt by the end of the year. And if it's positive it will
• 16:27
  open a number of opportunities for us given we have also this
• 16:32
  I-25 molecule. But let's one step at a time.
• 16:38
  I hope this gives you a good view on what we see as a
• 16:42
  potential of it. Does Yeah, Well, yeah, you took
• 16:48
  a few questions out of my my mouth actually Frederick with
• 16:50
  with that because I was going to ask about the miss indication
• 16:54
  expansion potential. But it's interesting how you
• 16:56
  view the TL1A monoclonal as sort of that, I guess it de de risks
• 17:03
  us bispecific, but also you just keep your eyes up open for
• 17:08
  potential different uses outside of IBD.
• 17:10
  Because yeah, like you say, it's a super competitive race, that
• 17:14
  one and one where there's obviously front runners who are
• 17:19
  much further along the track, right, naturally.
• 17:23
  And I know big pharma moves slower than biotech at times,
• 17:26
  but there's a limit, I guess to how much you can catch up if a
• 17:31
  company's in Phase 3 for sure. Nice.
• 17:35
  Do you, do you want to run through sort of where you're at
• 17:37
  with the programs at the minute? Obviously you started phase one
• 17:41
  for both 002 and 003, right? N001 now.
• 17:48
  Oh, have you? Oh nice.
• 17:49
  Yes. So all three compounds are now
• 17:51
  in phase one. The most advanced is BIN 002,
• 17:57
  the tier one half life extended monospecific drug for which we
• 18:01
  already have complete enrolled SAD and MAD and we have now a
• 18:07
  good understanding of how the drug behaved.
• 18:10
  We feel very confident that it would support dosing interval of
• 18:15
  three to six months. The second most advanced is the
• 18:20
  bispecific BN003TL1AI23P19. We have fully enrolled the
• 18:28
  single ascending part of the phase one healthy volunteer and
• 18:32
  we'll have some early results by the end of the year for sure.
• 18:37
  And last but not least, the 25 antibody B001 which for which
• 18:43
  we've just initiated 2 weeks ago or last week phase one.
• 18:49
  Oh, exciting, that's cool. And and getting away from the
• 18:53
  assets slightly, but, but more on AI guess a rounded picture
• 18:57
  of, of, of the company. Obviously it's not possible
• 19:00
  without the science, but it's also not possible without the,
• 19:03
  the team and ultimately the the money driving that progress as
• 19:08
  well. We touched on the guys at suffer
• 19:11
  Nova at the beginning, but obviously more recently you guys
• 19:15
  were in the news over summer because of the huge Series A you
• 19:19
  announced multiple different top EU and USVCS coming on to for
• 19:25
  that ticket. And I wanted to ask you
• 19:27
  obviously as a first time CEO, how you how you found that
• 19:33
  process, Frederick, because obviously it's it's very
• 19:36
  different to what you would have been involved in at Sanofi
• 19:39
  previously and any learnings you you sort of took from that
• 19:43
  process as well? For me, it's been quite a
• 19:48
  journey and it's my first time. So I don't really have any
• 19:53
  reference points to, to, to be able to tell you how it went.
• 19:56
  I think it went well because we got more than what were
• 19:59
  initially planned and we started toward the end of 2025.
• 20:03
  And I believe that at the time the funding environment was a
• 20:06
  bit challenging. Now I was lucky to started with
• 20:11
  a with a Sofi Nova, which is clearly a a respected name and
• 20:16
  and the fund which has a very significant outreach.
• 20:21
  It happened that our initial traction came from the French
• 20:26
  ecosystem because Jaito which is the other big venture capital
• 20:33
  firm right now in France quickly joined to Co lead the Ceresia
• 20:38
  together with Sofinova Partners. We also had quickly Sanofi
• 20:44
  Venture who came as a corporate, which also I think helps
• 20:49
  legitimize the project and provide some big Pharma
• 20:52
  validation of the relevance of the plan.
• 20:57
  And that's how it it it started. And then we were able to add up
• 21:01
  a few, a few a few more funds. Lessons learned is that you need
• 21:06
  to be persistent. You still have more no than yes
• 21:11
  getting to yes. It's quite a tedious profile
• 21:13
  process in that there's a lot of governance hoops Q and as, which
• 21:20
  is not so unlike what you experience at time in the big
• 21:23
  pharma space. But eventually the outcome is
• 21:26
  quite different. So for me, it's been very
• 21:28
  interesting in that I really got to meet a number of of investors
• 21:33
  and lots of different funds and there's no two funds alike.
• 21:37
  They all have different views, different people, different ways
• 21:40
  to look at it, different ways to understand the science or
• 21:42
  different perspective on the science.
• 21:44
  There are different time in the fun life, right?
• 21:47
  Whether they're early, late, they have different
• 21:51
  sensitivities to the overall environment.
• 21:54
  So I found it extremely enriching for me.
• 21:57
  It's been a big learning experience and I met a, a, a, a
• 22:02
  number of, of great people, some of whom have joined the, the
• 22:07
  current syndicate, some who have not because for various reason.
• 22:10
  But I'm sure we'll speak again later.
• 22:14
  Yeah, sure. And and I guess it never hurts
• 22:17
  having a name might suffer over investing early to open a few
• 22:22
  doors in that sense as well. But I mean, look, it's, I think
• 22:25
  it's France biotech's biggest ever Series A, right.
• 22:29
  So an awesome accolade to have. And I guess like you mentioned
• 22:33
  the guys at Sanofi coming on, very helpful to have that
• 22:36
  corporate back in particularly from, you know, a company who in
• 22:41
  the space, right like developing similar molecules themselves to
• 22:45
  a degree. So I mean, yeah, definitely
• 22:48
  helpful. You obviously none of it
• 22:52
  possible without the team that you're building as as well.
• 22:56
  I was keen to touch on because I know you've lived and worked in
• 22:59
  the US before as well. You're obviously based in in
• 23:02
  Paris now. And what is the plan for
• 23:04
  development now? I guess you've got some,
• 23:06
  obviously two of the biggest French VCs on the ticket.
• 23:10
  Are they keen to see you build out a a big presence in Paris
• 23:14
  and keep it European or are you looking across the pond?
• 23:17
  What? What's the perspective?
• 23:19
  I think the perspective is, you know, we are indeed a French
• 23:23
  company and we are incorporate in France, but the perspective
• 23:26
  is that we are a global company. I mean, the drug business is a
• 23:29
  global business. When you develop a drug, it is
• 23:33
  meant to be developed internationally, be it at the
• 23:36
  time of the treating code development or where you conduct
• 23:40
  your clinical trials or eventually when where it would
• 23:44
  be commercialized. We all know that the US is a
• 23:49
  very important place, not only because it is the main market
• 23:54
  down the road, but also because it's probably the largest talent
• 23:58
  pool and it's hard to dismiss it.
• 24:01
  So the the team is is is, you know, the the company is
• 24:06
  incorporated in France, the team is spread across France, Europe
• 24:12
  and the US. We also already have a number of
• 24:16
  of of associate in the US and it really come down to the network
• 24:22
  I had coming into this project. I spent as I said more than 10
• 24:27
  years with Sanofi and Sanofi is a French company, but it is a
• 24:30
  truly global company. We had multiple sites in
• 24:34
  multiple region of the world and as a result I knew people in
• 24:37
  multiple countries and that was my primary network.
• 24:41
  Some of these people have less than a fee to start their own
• 24:46
  journey freelance. Others have gone to other
• 24:49
  company and have got to know other people either have less
• 24:52
  than a few to the biotic space and have also made different
• 24:55
  type of connections. And throughout this network
• 24:59
  where we I was able to to build the initial group of people who
• 25:06
  supported the diligence and then the initial work on the project
• 25:09
  now really run the operations. And it started with a very, I'd
• 25:15
  say nimble structure, primarily relying on external consultant,
• 25:20
  right, mostly part time because there was not enough.
• 25:23
  And as we fund raised and as our operations have grown, some of
• 25:29
  these consultants have remained with us increasing the, the,
• 25:33
  the, the workload. We have made a few recruitments,
• 25:38
  but we managed to have in a matter of months a fully
• 25:41
  operational RND team or clinical development RND team thanks to
• 25:47
  like to the flexibility that these models offer you.
• 25:51
  Going forward, you'll probably evolve a bit the model, but for
• 25:55
  now this gives us the time to really understand what are
• 25:58
  exactly I need in terms of commitment, in terms of
• 26:00
  location, in terms of specific profile and we can build from
• 26:04
  that. Yeah, nice.
• 26:06
  Interesting. I guess one of the reasons I was
• 26:09
  asking is I know at least because it's often over a part
• 26:12
  of the European like coalition, as it were, for, you know, BCS
• 26:18
  like Bobby and involved as well in terms of trying to get
• 26:22
  companies to yes, capital flowing into early biotech, but
• 26:26
  also companies trying to stay here a little bit longer as well
• 26:29
  and and build up operationally, should we say so yeah, it'd be
• 26:33
  interesting as as a company who've raised a ton of money as
• 26:36
  it were, you know, France's biggest Series A in biotech
• 26:40
  ever. It'd be interesting to see how
• 26:42
  how feasible you think it is to grow the company in Paris
• 26:45
  because there's been some success stories, but there's
• 26:47
  been some, some challenges as well for sure.
• 26:50
  Cool. Well, look, Frederick, thanks
• 26:51
  for coming on and giving the overview to Bayonera.
• 26:53
  I think it's a really interesting story to shine a
• 26:57
  light on and looking forward to seeing some more news from you
• 27:00
  guys, I guess later this year, early next.
• 27:03
  Absolutely. It's been a pleasure having a
• 27:07
  chance to share what we do at Bayonneera.
• 27:09
  Tell our story and I look forward to telling you more
• 27:13
  shortly. Yeah, absolutely.
• 27:15
  Awesome. Cool.
• 27:16
  Well, Frederick, thanks for the time.
• 27:18
  Catch you soon. Thank you very much.