Latest / The BioHub - by Avetix / Episode 186 - Derek Small - Founder, Managing Director Luson Bioventures

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Episode 186 - Derek Small - Founder, Managing Director Luson Bioventures · The BioHub - by Avetix

• 0:06
  So welcome back to another episode of the Bio Hub and
• 0:08
  Avetics podcast. Today I'm joined by Derek Small,
• 0:12
  founder and Managing Director of Lucen Bio Ventures and a long
• 0:16
  time biotech founder and CEO. Over the last two decades, Derek
• 0:20
  has been at the forefront of venture creation in biotech,
• 0:23
  founding and leading multiple companies across neuroscience
• 0:26
  and CNS drug development. Through Lucen, he's helped build
• 0:30
  and scale businesses from inception, raising over a
• 0:32
  billion dollars in capital and taking several companies to
• 0:36
  significant exits and public markets.
• 0:38
  In this conversation, we talk about venture creation versus
• 0:41
  traditional VC, why neuroscience continues to be his focus and
• 0:46
  what's changed in the current biotech market, and how he
• 0:49
  thinks about building companies in tougher cycles.
• 0:53
  Pleasure to have you, Derek. How are you?
• 0:55
  Oh, thanks, Max. No, it's great to be here, man.
• 0:57
  Appreciate it. For sure.
• 1:00
  Let's just start with your background.
• 1:01
  So you spent the last two decades founding and scaling
• 1:05
  biotech companies, which I kind of mentioned in the
• 1:08
  introduction. What originally drew you to
• 1:12
  venture creation instead of a more traditional VC path?
• 1:17
  Yeah, well, you know, I'm not sure I have anything traditional
• 1:22
  honestly kind of in my background because I I have an
• 1:25
  advanced degree. I have an undergraduate degree
• 1:28
  in business from small private college and went right into
• 1:33
  investment banking at Morgan Stanley.
• 1:35
  And then I did look into kind of AVC pathway, but it was on the
• 1:39
  tech side. It was at a company called EMC.
• 1:42
  And, you know, neither of those were really that appealing to
• 1:47
  me. But but we were six.
• 1:49
  I was, you know, able to kind of operate in that mode
• 1:53
  untilthe.com bus. So this is quite a while ago.
• 1:55
  This was, you know, late 90s and then early 2000 after the.com,
• 2:00
  you know, kind of implosion in 2001, I was approached by a
• 2:04
  scientist to help raise capital for a cancer therapy that he
• 2:09
  discovered. And I thought this would be, you
• 2:12
  know, hey, easy. I'd already raised a bunch of
• 2:15
  money and started companies on the tech field.
• 2:17
  And you know, so I, I was like, yeah, sure, I'll, I'll help.
• 2:21
  And it'll be everything I just did in tech and I can bring it
• 2:24
  into biotech. And then I realized that that
• 2:26
  actually was a horrible fallacy that because zero, there were 0
• 2:32
  investors in tech that were looking at biotech.
• 2:35
  So, and, and none of the skills were transferable.
• 2:37
  Really all my sales projections for tech companies made zero
• 2:42
  sense. And you know, when we had a
• 2:43
  preclinical discovery stage biotech company that wasn't
• 2:47
  going to see a sale for 15 years and after raising a billion
• 2:52
  dollars, you know, so it was, it was a learning experience that
• 2:56
  I, I honestly kind of embraced and fell in love with.
• 3:02
  That first company was my first biotech company called Simaphor
• 3:07
  Pharmaceuticals that we launched in 2002 and it was the first Pi
• 3:12
  3 kinase inhibitor company. So at a time when so many things
• 3:15
  were changing in the biotech field, I had no idea.
• 3:19
  I was like 26 years old or something like that.
• 3:22
  So, and I fell in love with biotech.
• 3:26
  That's where I say I got addicted to drugs was what was
• 3:28
  right there. And I had company I, I, I never
• 3:33
  went back to anything else. I stayed in biotech from there.
• 3:37
  I mean, it's such a that that, you know, timing of PI3 kinase
• 3:41
  in biology was just being, you know, discovered there were no
• 3:46
  drugs targeting it that were advanced.
• 3:48
  So we were the first and then we were the first into the clinic
• 3:51
  with this. And because I'm based in
• 3:54
  Indianapolis, the, and I've always been, you know, kind of
• 4:00
  here and around here and my family's from here.
• 4:02
  So it was very difficult to raise capital.
• 4:06
  It was a neat time because some people were transitioning for
• 4:09
  me, like Lily right then that ended up being major mentors and
• 4:14
  contributors and and partners for me going forward.
• 4:17
  Richard Demarki just retired, Guswantnabi just retired, Homer
• 4:21
  Pierce just retired, and then a whole wave of other neuroscience
• 4:25
  leaders retired too. So it was, I didn't know it
• 4:28
  then, but you know, that was the perfect timing to kind of get
• 4:31
  going. The cancer field was just
• 4:33
  starting to evolve too is before Gleevec was approved.
• 4:36
  So targeted therapy and oncology didn't exist when we started
• 4:40
  that company and and then that kind of all happened in the same
• 4:44
  time frame. It was a biology that I had to
• 4:47
  learn. Their resources weren't there.
• 4:50
  It was hard to raise capital. So I was required to do things
• 4:55
  in a way that most non biotech people would never get to do.
• 5:00
  I ended up actually writing multiple grants to the to the
• 5:07
  because it was so hard to raise capital, but that that forced me
• 5:09
  to learn the science. And then after successfully
• 5:13
  getting a few grants awarded, we needed to advance the drug into
• 5:18
  the clinic. So and we didn't have the money
• 5:20
  or the team to kind of really do that.
• 5:22
  So I actually became head of regulatory and clinical affairs.
• 5:26
  I learned through a network of, you know, great advisors.
• 5:29
  We were epitomizing virtual company development before that
• 5:35
  was a thing because we had to, we didn't have the money to
• 5:38
  really build a team and, and, and go out that way with, you
• 5:43
  know, kind of a more sophisticated framework.
• 5:46
  So I was forced to learn how to write an Ind and, and interact
• 5:50
  with the FDA and then we put a clinical protocol together and,
• 5:53
  and launch the 1st clinical trial.
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  I always had great experts around me, but they were
• 5:57
  fractional, you know, part time people, the only full time
• 6:01
  person on that side of the equation.
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  Although of course we had science, great scientists and in
• 6:07
  the company too. So that's really where, you
• 6:10
  know, it all kind of began for me.
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  And why I fell in love with biotech and, and the richness of
• 6:16
  that biology. I had no idea at the time, of
• 6:17
  course, is what kind of opened my mind to how things could work
• 6:24
  in a similar fashion and other, you know, disease categories,
• 6:28
  others, you know, chemistry modalities for drug discovery
• 6:32
  and development. You know, this is where I met
• 6:35
  one of my, you know, favorite Co founder drug hunter partners at
• 6:39
  Richard Demarke. And yeah, that kind of set me in
• 6:43
  a on a pathway that, you know, led me to to today.
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  And Richard and I start companies and talk about ideas
• 6:50
  to this to this day. And as I mentioned, I was just
• 6:53
  down at a a lecture. We're just establishing a new
• 6:56
  class at Indiana University focused on biotechnology and
• 7:01
  drug development. And yeah, it's exciting time.
• 7:05
  Yeah, for sure. And it's a, it's a really
• 7:07
  interesting path. And then you you look at Lucent,
• 7:12
  you've been pretty. Deliberate about venture
• 7:15
  creation versus venture capital. Yeah, go ahead and.
• 7:17
  You know, and I, I think that that's really, I've always been
• 7:22
  an operator over an investor, but thinking like an investor, I
• 7:27
  found to be important and kind of intellectually honest for me,
• 7:31
  since I'm not a scientist, I wanted to make sure that we were
• 7:36
  thinking of this as much about an investment thesis, but
• 7:40
  appreciating the science and, and to really do that and play
• 7:43
  that through, I felt like I, I needed to be on the operating
• 7:47
  side versus just the pure investment side.
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  And so, and I've always had kind of attraction to that and, and
• 7:56
  building teams and, and trying to, you know, the, you know,
• 7:59
  with the goal of leading organizations and, and building
• 8:02
  cultures that, you know, can kind of hopefully align with,
• 8:08
  you know, that vision or goal of, of, you know, having not
• 8:14
  only deeply scientific roots that, you know, drive science
• 8:19
  towards drug development that can help patients, but also
• 8:24
  hopefully in a highly ethical, you know, you know, North Star
• 8:29
  type of cultural strategy that aligns business and science.
• 8:35
  That's always been something I felt pretty core for me.
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  And, and, and aligning incentives is, is kind of a, you
• 8:41
  know, a deep perspective that I have that I, I, I like to, you
• 8:48
  know, make sure it's part of all of our companies.
• 8:50
  So leading those just makes it easier to maintain that without
• 8:55
  having to try and, you know, imprint that on a new person,
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  especially when I was so young getting started.
• 9:02
  So then it's just kind of like rinse and repeat.
• 9:04
  You know, I've started several companies and, and they've been,
• 9:08
  you know, most of them have been, you know, relatively
• 9:12
  successful. So bringing in a new CEO has
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  been, you know, pretty straightforward.
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  It's just been different timing and different circumstances, but
• 9:21
  that's, that's created this more organically than necessarily.
• 9:24
  I, you know, I definitely didn't start off in 2002 thinking I was
• 9:27
  going to do this as we've done it to the day.
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  But but yeah, that's that's kind of how I think about it as I
• 9:35
  look back. And and then there's the other
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  interesting part that because of the way you've worked, you work,
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  you often have to wear 2 hats at once.
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  How do you then manage those roles?
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  Yeah, there is a, you know, I think I, I tried to govern all
• 9:52
  decisions frankly by my faith initially, which is make, you
• 9:58
  know, decisions that are in the best interest of the order of
• 10:01
  the organization. So that, I mean, you know,
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  that's how kind of my faith dictates how we should make
• 10:10
  decisions and and respect structure.
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  But in a way that I think could just be more about doing the
• 10:16
  right thing. You know, this idea of, you
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  know, it's never the right time to do the wrong thing, I think
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  has always been kind of a a true notice for me.
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  And so, yeah, those that that just gives me a a framework for
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  leading the organizations. Yeah.
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  And then there's there's the part that you are now focused
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  on, which is neuroscience. Why?
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  Why has CNS been such a consistent focus for you,
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  despite how challenging the space has been?
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  Yeah, well, so I didn't know how, you know, it was all
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  challenging to me. So it, it, it, it's one of
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  those, you know, where I just didn't know what I was
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  necessarily getting into. In 2007, I met a scientist up at
• 10:56
  Northwestern. His name's Joe Moskal.
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  And Joe had discovered this idea of using a very small peptide
• 11:07
  for modifying really complex, you know, neuro activities.
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  And the peptide itself, you didn't make a ton of sense as I
• 11:16
  look back at it as a 5 minute Tetra, 5 minute plasma half life
• 11:21
  Tetra peptide, that's IV only. And we were going to take it
• 11:23
  into the chronic depression. And so at the time, it seemed
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  very unlikely, but that, you know, the experience actually, I
• 11:33
  had with at Semaphore, we use a tetrapeptide to conjugate to a
• 11:38
  small molecule and, and provide kind of a separation from PK and
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  PD, meaning, you know, we were able to target and, and increase
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  the life of, you know, the duration of the effect of the
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  molecule without, you know, necessarily matching the actual
• 11:55
  PK of the pharmacokinetics of the molecule.
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  So this small peptide that was quick in and out, you know, it
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  didn't instantly not make sense to me.
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  And so then it made it I think made me be a little bit more
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  honest with looking at the pharmacology, understanding the
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  data and then, you know, be willing, I think and myself and
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  my advisors, I had some great advisors around me too, that
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  were excellently neuroscience leaders that were just pretty at
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  this point. And they had been retired for a
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  while. So they were pretty honest
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  scientists. And so when they saw that, you
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  know, saw the data without jumping to conclusions about the
• 12:33
  molecule or the pharmacokinetics, they realized
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  that, wow, this drug was actually modifying multiple
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  behavioral in vivo functions for weeks, not just the minutes that
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  it was there as a plasma half life.
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  And so we had enough data together to convince them.
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  And then it was just empirical. We were did an experiment after
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  proof, experiment proof, experiment proof.
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  Then we started to see proof of concept happen in in clinical
• 13:02
  trials with drugs like ketamine. And then we were able to get our
• 13:07
  drugs in the clinical trials and start to show similar profiles
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  and what that was doing then. But you know what really
• 13:14
  imprinted me though? There were two things in those
• 13:17
  two companies, the oncology company and then what happened
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  later in in this company called Norax, the first neuro company
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  was the patient responses in those clinical trials were
• 13:29
  dramatic. So my first patient in that
• 13:32
  oncology company, she was a you know, 27 year old female with
• 13:39
  stage 4 gastrointestinal stromal tumor had not responded to any
• 13:43
  therapy. I mean, ultimately was terminal
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  and she responded to the first dose that we gave her in a way
• 13:51
  that we, you know, she stabilized and then it actually
• 13:53
  ended up on that first dose for over 5 years.
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  And so that stabilization and that kind of patient impact was
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  a big imprint for me. And then Fast forward to Norax
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  that the first clinical trial we did, it was really unusual.
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  So it's single dose clinical trial where we were looking for
• 14:14
  a 24 hour onset, which was pretty unique at the time,
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  although we we know that to be more possible now with many
• 14:21
  different drugs and psychedelics and what have you.
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  But it wasn't then. And so in what was happening was
• 14:28
  as we're waiting on the data to come in, we were getting calls
• 14:31
  from patients saying, Hey, you know, this drug and I have them
• 14:34
  still on my phone. This drug has literally changed
• 14:37
  my life and I can't go back to the way I was before.
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  How can I stay on your drug in these clinical trials and these
• 14:44
  things just, you know, kind of change, you know, how how I
• 14:49
  viewed this business and what my career might be to be something
• 14:54
  that was to absolutely more about trying to to help the
• 14:57
  patients that need these therapies and think deeper about
• 15:00
  the science and and so on too. So that changed dramatically for
• 15:05
  me and my my interest in what types of drugs development to
• 15:09
  develop. Now I brought in a new CEO there
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  as a company got bigger just because I felt like I was not
• 15:14
  really prepared to be. We're going to take it public.
• 15:17
  We had a confidential S1 on file.
• 15:19
  So, and I just didn't, I'm so young, I'd never done any of
• 15:24
  that. So we brought in a, a new CEO
• 15:27
  that was supposed to kind of set it up to go public ultimately,
• 15:31
  you know, and I stayed on the board there, but you know,
• 15:34
  ultimately we sold the company instead of going public.
• 15:37
  And I started an HPV company and we took that public before that
• 15:40
  company and I became CEO of that.
• 15:42
  So, you know, I, I guess there were different plans for me than
• 15:45
  I thought I had for not taking a company public and being a
• 15:49
  public company CEO that derailed my idea of staying in the neuro
• 15:55
  space. But it became such a juggernaut
• 15:58
  of a company. We ended up going public rapidly
• 16:01
  in this hepatitis B company called Assembly Biosciences,
• 16:05
  raised 3/4 of a billion dollars in a in a few years, advanced
• 16:10
  into multiple clinical trials or developing drugs in China.
• 16:13
  And you know, just really tremendous experience and
• 16:16
  progress that I can't really replace that from building
• 16:20
  relationships and understanding how to run a public biotech
• 16:24
  company and what have you. But as we were going through
• 16:27
  that around 20/16/2017, my father was had a major episode
• 16:35
  and was sent to the hospital with full code and being
• 16:39
  resuscitated. And that began kind of a new
• 16:43
  awareness that actually he was at the end stage of an early
• 16:46
  onset dementia that I guess I was just in denial of.
• 16:50
  Before that we had all the hallmarks that he was having
• 16:53
  those challenges. But, you know, we just all
• 16:57
  thought he was being lazy, getting belligerent, you know,
• 17:02
  not kind of being a good, you know, father and husband.
• 17:08
  So it just was, it's felt like it was a personal thing.
• 17:12
  And what we realized was it was absolutely structural for him.
• 17:16
  It was a, you know, dementia and, and I being became his
• 17:19
  primary care provider too. And as I was doing all this
• 17:23
  crazy, you know, flying around and that was super eye opening
• 17:29
  for me. And, and a reminder he ended up
• 17:31
  dying in in 2017 complications associated with that.
• 17:35
  And that was when I started my succession process for the next
• 17:39
  CEO at that company Assembly Biosciences.
• 17:42
  And I decided actually I decided in 2016 to get back into neuro
• 17:46
  from my loose on bioventures standpoint.
• 17:49
  And we, I started to build the advisory team back up.
• 17:52
  We actually launched a couple biotechs that I was not CEO of,
• 17:55
  I was just an investor and board member on and kind of got back
• 18:01
  into that pathway when I finally found the right CEO to bring in
• 18:05
  there. That's in 2019 where I went, you
• 18:08
  know, kind of fully back into 100% neuro for loose on bio
• 18:14
  ventures and started, you know, several of the companies that
• 18:17
  now we, we still are either operating or running today.
• 18:22
  Yeah. I mean, that's incredible.
• 18:26
  And I think neuro is interesting as well in the fact that
• 18:29
  especially since you've been part of it, it's changed a lot.
• 18:33
  And I said it was a struggle, but like that's becoming less
• 18:37
  the case as of recent when when you're looking ahead, what
• 18:41
  emerging trends or breakthroughs do you see redefining CNS?
• 18:47
  Well, so there's so many, there's so much good science
• 18:51
  going on right now in neuro IT. I agree with you.
• 18:54
  It really is an exciting time. If we're looking at the drug
• 18:57
  development in the right way, it's not as hard as people have
• 19:02
  thought historically because we have more tools.
• 19:04
  We're learning more about genetics, we're understanding
• 19:06
  the biology better, we're understanding patients better.
• 19:09
  We're actually trying to pay attention more to pathology
• 19:13
  instead of just symptom, symptom mythology.
• 19:17
  And I think that's when, you know, that's really when the
• 19:20
  breakthrough happened in oncology.
• 19:22
  Not that they were paying attention to symptoms in
• 19:24
  oncology so much as, but they were just going after blunt
• 19:28
  force objects. They didn't have a lot of
• 19:29
  genetic or, or kind of biological insights to each
• 19:33
  types of cancer, right? We didn't know what her 2
• 19:36
  positive EGFR negative triple, you know, whatever breast cancer
• 19:41
  was at that point. And so, but I got to see that
• 19:46
  happen, right. I mean the Flip 2 positive
• 19:49
  gastrointestinal stromal tumors that were the key cancer driver
• 19:54
  responder it to Gleevec and that approval as the first biomarker
• 19:59
  targeted approval subpart H progression free survival and
• 20:03
  oncology that happened while I was starting a clinical trial
• 20:06
  with the PI3 kinase inhibitor. I knew the whole team getting
• 20:09
  that going. I mean, so there were there's a
• 20:11
  lot of analogy that we can. I think now see happening in
• 20:16
  neuro where we are understanding biology better.
• 20:19
  We're we're starting to measure it and and pay attention to it
• 20:23
  in a way that you know, we're getting biomarker approvals.
• 20:26
  We had a first subpart age approval in the past few years
• 20:29
  and we've had a couple other biomarker based approvals and
• 20:32
  mostly neurodegeneration and, and, and neurology like epilepsy
• 20:38
  areas, Huntington's disease and so on.
• 20:41
  Alzheimer's too, of course, from a biomarker standpoint.
• 20:44
  And you know, and we're starting to see it in psychiatry to the
• 20:48
  point where, you know, it's, it's all starting to converge
• 20:51
  and make sense. So that's the field, right.
• 20:55
  So for me though, I actually took it very personally and I'm
• 20:58
  looking at my, you know, not, not to be kind of like in the
• 21:02
  clinical sense. I'm looking at my father as he
• 21:05
  you know, and I'm taking care of him for days or you know, at a
• 21:09
  time, sometimes ours type of situation.
• 21:13
  And I could see two things as he would code have to be
• 21:17
  resuscitated and then the time it took to recover, which
• 21:20
  happened unfortunately like quarterly for the last two years
• 21:23
  of his life. And each time it was longer and
• 21:26
  longer and longer, but as his recovery.
• 21:29
  And so, but as I saw that, I could see two things.
• 21:33
  I could see his synapse is not functioning.
• 21:36
  I don't know how to explain it other than that was what I could
• 21:38
  see that. And maybe it's because of my,
• 21:41
  you know, experience at Norax and seeing a drug that could
• 21:44
  just boost synapse as quickly, give you a response within 24
• 21:49
  hours. I'm like, man, I would love to
• 21:51
  give that to my dad. So after he's recovered, maybe
• 21:54
  he can remember my name, you know, sooner and, or if at all
• 21:59
  at towards the end. And, and then I could see too,
• 22:03
  it wasn't just synaptic function, it was something else
• 22:06
  was going on that was not allowing that to happen or
• 22:09
  recover faster. And for me, I could can't say it
• 22:12
  any better way, but I could see neuro inflammation.
• 22:15
  I can see inflammation in the brain that was happening in a
• 22:17
  way that wasn't the rest of his body.
• 22:20
  So I could see those two things as new situation and for him and
• 22:27
  that really started me on a path to really dig into that science
• 22:31
  and be like, is this, you know, am I just seeing this?
• 22:34
  Is there any real science here? The genetics were starting to
• 22:37
  come out, the pathological understanding of these diseases
• 22:41
  starting to get better understood too.
• 22:43
  And lo and behold, the two biggest hits so-called in that
• 22:48
  hallmark biology, understanding of genetics and pathology and
• 22:53
  symptoms too, actually, what happens?
• 22:55
  What do you see when, what correlates best with the
• 22:59
  cognitive decline and Alzheimer's, for instance?
• 23:01
  Well, it's synaptic dysfunction and neuro inflammatory markers
• 23:06
  and all those genetics kind of precede that.
• 23:08
  And in a way that has now made it more the state-of-the-art.
• 23:14
  Everybody, you know, sees this as the next area we should
• 23:17
  figure out. That became something that I, I
• 23:20
  started focusing on in 2017 and now we only focus on companies
• 23:26
  that in impact or can measure synaptic changes in synaptic
• 23:31
  function or enhancing synaptic function or reducing neuro
• 23:36
  inflammation in these diseases. And these cross, you know,
• 23:40
  psychiatry and neurology, It's, it's really both of those, if we
• 23:44
  do this right from a drug development standpoint.
• 23:47
  Yeah. And that just really reiterates
• 23:49
  how exciting Neuro's becoming, which is awesome.
• 23:55
  I'm going to completely change the topic now as well, Derek.
• 23:59
  And it's something. So we actually met at JP Morgan
• 24:03
  in San Francisco in January, and we talked about this a little
• 24:06
  bit. Outside of Lucid and company
• 24:09
  building, what do you spend time on that helps you stay sharp or
• 24:13
  brings different perspective into your work?
• 24:18
  Well, you know, my wife and you know, would say that I only
• 24:25
  work, which isn't true. And because the I only do, but I
• 24:30
  do only do two things. I I basically, you know, I, I, I
• 24:33
  work, of course I exercise and try to stay fit and, and and
• 24:38
  mindful of, of my longevity. But for the most part it's
• 24:42
  family. Yeah.
• 24:43
  That's, you know, so when I unplug, it's to be with my
• 24:49
  oldest daughter Madison, who just graduated from Purdue
• 24:52
  University, or my son who's in the middle of the three of my
• 24:56
  kids, who is a junior at Purdue University and my 14 year old
• 25:02
  daughter, as you know, I was with yesterday and and my wife
• 25:06
  Amy, whom I've been married to since the year 2000.
• 25:10
  So that means 26 years of marriage and that's all I do.
• 25:15
  So, and I love that part. I the opportunity to, to spend
• 25:19
  time with my family and, and, and they don't, they're not
• 25:23
  necessarily. I mean, my kids are starting to
• 25:25
  get into biotech now as they move into careers.
• 25:28
  But for the most part, that's not what we talked about.
• 25:31
  We know when, when we're as a family, we're spending much more
• 25:35
  time away from that. And that gives me enough of
• 25:37
  separation, I think, from church and state, so to speak.
• 25:41
  Yeah, I love that. I mean, yeah, it's important,
• 25:44
  right, For sure. And that brings us to to my
• 25:48
  final question, which is a question I asked every one of
• 25:51
  the guests on the Bio Hub. And it's one that you've you've
• 25:54
  built up a little bit of suspense on as well before we
• 25:58
  started recording. If if you could have dinner with
• 26:01
  any scientist or innovator, past or present, who would it be and
• 26:04
  why? So I love that question, as you
• 26:10
  know, and you sent that ahead before and I'm really glad that
• 26:12
  you did because I would be struggling right now because I,
• 26:16
  when I, when I saw that come in, I and I was driving back from
• 26:20
  this class actually, and with Richard and Bloomington, I'm
• 26:24
  like, wow, what, who, who would it be?
• 26:27
  Because I'm so blessed actually, to have just such an
• 26:30
  extraordinary cast of scientists around me already as you can.
• 26:36
  I don't have my website published yet, but I'm, I'll put
• 26:39
  it out there. But my key advisors of Lusan
• 26:42
  Bioventure are, you know, Nobel Prize winners and hopefully soon
• 26:49
  to be another Nobel Prize winner and, you know, drug hunters that
• 26:54
  have have been able to advanced several, you know, drugs to help
• 26:59
  patients. And and since that's kind of my
• 27:01
  North Star for these things, that's just means so much.
• 27:04
  So it's, it's hard for me to think about this.
• 27:06
  And what I actually would do though, if you can let me go be
• 27:13
  a little bit different than that one person is, I'd actually, I'd
• 27:18
  want to have a group of people at my dinner, to be honest with
• 27:23
  you. I'd want to have three dinners,
• 27:24
  But, and let's do it, I won't, I don't have to go to all three
• 27:30
  dinners. I can give you the first one,
• 27:32
  which would probably be enough. And I have, so I'm a historical
• 27:36
  scientist that you know, you may know, you may not.
• 27:42
  And then kind of my a cast of scientists that would actually,
• 27:46
  I think try to help us capture some of this concept of what
• 27:50
  we're working on right now, what we just talked about for
• 27:52
  synaptic function and neuro inflammation.
• 27:55
  These aren't just like, you know, mechanisms for making new
• 27:59
  companies. These are what I think are going
• 28:03
  to be insights that can, if we, if you know, if we're paying
• 28:07
  attention to them, what we've seen in with the GLP 1, you
• 28:13
  know, revolution essentially with cardio metabolic disease,
• 28:16
  is that if you, if you strip that down to what's happening,
• 28:20
  these aren't just like, you know, obesity drugs or whatever
• 28:22
  they're they're changing Physiology for people, right?
• 28:26
  We're reducing long term cardiovascular disease and, you
• 28:34
  know, it's now been approved for, you know, these chronic
• 28:39
  liver diseases and of course diabetes.
• 28:42
  And so and what that is, is it's a it's a, it's a network
• 28:45
  phenomena. So really metabolism had met
• 28:48
  and, and, and you know, interacting or, or normalizing
• 28:52
  that with these incretin peptides and not just one right.
• 28:57
  It's not just GLP one, it's GIP is Glucagon.
• 28:59
  It's kind of it's this discovery of this network phenomena that
• 29:04
  actually if you test that, and this is what was shown, this was
• 29:07
  Richard Demarchy has shown, this is if you test that in
• 29:11
  preclinical models, right, you actually see a, a dose response
• 29:15
  and a potency change in animals that when you test that in
• 29:19
  humans, it's this, it's almost, you could almost lay it on top
• 29:23
  of each other. And that's because there's this
• 29:25
  evolutionary conserved biology that, this network biology that
• 29:31
  this impacts. And then so instead of targeting
• 29:35
  adipose tissue, right, for losing fat, this is a, a, a
• 29:41
  fundamental mechanism of, of, of Physiology that wouldn't you,
• 29:45
  you know, tweak that you can actually change the whole system
• 29:48
  to better the outcome. And I just love that concept.
• 29:52
  And actually that's really what drives this, this idea of
• 29:56
  neuroinflammation and synaptic function for me in a way that
• 29:58
  says, Hey, this is a network phenomena.
• 30:01
  And actually one of the few core biologies that predates our
• 30:07
  metabolism, you know, conservation across from sea
• 30:11
  elegance to, to humans is neuronal function.
• 30:16
  So we have to to have, you know, we have to exist, we have to
• 30:19
  have cognition. And there's a few 100 years more
• 30:23
  evolution. So, but it's not how we really
• 30:25
  think about it yet. So my dinner would be to put a
• 30:29
  couple of those ideas together and and really, you know, the
• 30:33
  synapse as a biology has been awarded, you know, many Nobel
• 30:43
  prizes actually since the 1800s. And so that would be 1
• 30:48
  scientist. The first Nobel Prize for a
• 30:50
  synapse related discovery was Robin Law.
• 30:56
  And and so if you, if you know, if you Google that name, if you
• 31:00
  don't already know him, he's the one who's drew the first
• 31:02
  pictures of the synapses and neurons and you know about so
• 31:08
  much really neat art. And he ended up, you know, so
• 31:11
  there's all sorts of art if you do, you know, search synapses
• 31:13
  and Kahali, Ramoni Kahali, you'll see these beautiful
• 31:17
  pictures and, and they're the exact same pictures of the
• 31:21
  images that we see today. So he he would be fun to talk
• 31:25
  with. For how that would work.
• 31:27
  I'd bring in my current Co founder of Sendeo 2 Nobel Prize
• 31:33
  winner Tom Sudoff. Tom is the most recent Synapse
• 31:38
  Nobel Prize winner in 2013. And really his work is, but it
• 31:43
  it's, it's actually all connected.
• 31:45
  The three other Nobel Prizes, they're basically just building
• 31:48
  on them, on each other. They're all connected and they
• 31:51
  all validate each other really too.
• 31:53
  So that becomes clear. But I want to click that into
• 31:57
  more of a, so that the, the, the next person is more of a neuro
• 32:02
  inflammation person. And I, I've chosen one.
• 32:06
  There's many to think about, but there's no Nobel Prize yet for
• 32:09
  this. But it'd be Beth Stevens from
• 32:12
  Harvard who really has established this concept of
• 32:16
  microglia and astrocyte maintenance, not just pruning or
• 32:20
  or damage to set synapses, but maintenance saying that these
• 32:25
  can be go both ways. And then I would pull in Richard
• 32:29
  Demarke, who established this as a network biology phenomena and
• 32:36
  metabolism. And then just and just let them
• 32:39
  explain, you know, try to really solve helps to solve.
• 32:43
  You know how this could could all be the last person I'd add
• 32:46
  actually is is what pulls the neuro piece together of like
• 32:50
  this isn't just some kind of academic or or opportunistic
• 32:55
  idea. We have human models for this
• 32:58
  concept that have been studied now genetically, longitudinally.
• 33:03
  And these are our centenarians or you know, the Super agers.
• 33:06
  These are 100 year plus individuals who are super
• 33:12
  cognitive. You know, actually probably
• 33:14
  score higher on cognitive scales than than you or I and they're
• 33:18
  100 year plus people. Those are studied by a woman in,
• 33:21
  in Denmark named Henny Holstidge.
• 33:24
  And she has really established this framework and all the
• 33:27
  genetics that that that she's discovered and the phenotype
• 33:31
  she's discovered are highlighted by synapse resilience and or
• 33:37
  resilience to neuro inflammatory activities too.
• 33:40
  So it kind of connects it all together and we could create a
• 33:44
  network, you know, phenomena that would say this might
• 33:48
  actually, you know, we might actually be able to live to be
• 33:52
  100 year plus. You know, even with these
• 33:54
  pathologies, we might have it in a lot of those patients.
• 33:56
  By the way, they have a beta pathology, they have Tau
• 33:59
  measurable phospho Tau 217 and they still are super cognitive.
• 34:04
  So it's possible to be resilient to those diseases, to not have
• 34:09
  depression, to not have anxiety, to not have neurodegeneration,
• 34:13
  even if you have the pathological signatures, if you
• 34:18
  can represent that phenotype and that.
• 34:20
  Yeah. So that would be my dinner with
• 34:23
  those. I got two more dinners that I
• 34:25
  would add to that, by the way, but.
• 34:26
  I love that you love this question so much and you could
• 34:29
  tell like the way you answered it, like we'll have to do 2 more
• 34:33
  episodes so that we can get the two more dinners.
• 34:35
  So you have to stay tuned. Yep, Yep.
• 34:39
  It gave me a really good idea too.
• 34:41
  I plan on, I plan on having those dinners actually.
• 34:44
  So. Well, do I get to come and and
• 34:47
  sit and listen at the side or? Yeah, you prompted the idea.
• 34:51
  I'll make sure. I'll make sure that you're
• 34:53
  you're involved. Sounds good.
• 34:55
  Well, look, it was an absolute pleasure to have you on, Derek.
• 34:58
  And look, we'll have to do it again soon for sure.
• 35:01
  Fun, Max, Thanks so much. I, I, I really appreciate the
• 35:05
  opportunity and, and love talking about this stuff and
• 35:08
  yeah, love to do it again. And look, everyone please like
• 35:12
  and subscribe to the bio Hub and and thank you so much again,
• 35:15
  Derek. Thanks Max.