Latest / The BioHub - by Avetix / Episode 60 – Devyn Smith – CEO Arbor Biotechnologies

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Episode 60 – Devyn Smith – CEO Arbor Biotechnologies · The BioHub - by Avetix

• 0:04
  So welcome back to the episode of the Bio Hub.
• 0:07
  Today, we're delighted to be joined by Devin Smith, who is
• 0:10
  the CEO of Arbor Technologies and a key figure in gene editing
• 0:14
  and regenerative medicine. With over 20 years of experience
• 0:17
  in biotech and APHD in genetics from Harvard, Devon leads
• 0:21
  Arbor's efforts to develop next Gen. gene editing tools.
• 0:25
  He also serves as a board member and former Chairman of the
• 0:27
  Alliance for Regenerative Medicine, helping to guide the
• 0:31
  industry's future. So join us today is Devin gives
• 0:34
  a run for his journey, the recent advancements at Arbor and
• 0:38
  his role as board member and former chairman of Alliance for
• 0:42
  Regenerative Medicine. So Devin, thanks so much for
• 0:45
  coming on. How are you I'm.
• 0:46
  Good. Thanks for having me, Tom.
• 0:48
  It's a pleasure to be here. Yeah, it's a pleasure to have
• 0:51
  you on as well. So let's jump into a little bit
• 0:54
  about you then. So can you talk us through your
• 0:56
  journey to get to where you are now and what inspires you to
• 1:00
  pursue a career in the biotech industry?
• 1:03
  Yeah, so I, I grew up in a small town in Utah.
• 1:08
  So I've probably more non traditional biotech background
• 1:12
  and in a, in a large family of 11 kids on a farm.
• 1:18
  And as a kid I was always fascinated with, we had a lot of
• 1:21
  animals and as you particularly chickens and as we breed
• 1:25
  chickens, you'd get different traits coming out.
• 1:27
  And so it fostered this real interest in genetics such that,
• 1:31
  you know, we used to, you know, you've got chickens that have
• 1:34
  feathers of these big hats or you have feathers on their feet
• 1:37
  and you can begin to breed them and, and generate all sorts of
• 1:39
  interesting mixes. And, and that I think's really
• 1:45
  sparked a real interest in genetics and biology.
• 1:48
  And, and so you're going through high school, I was very
• 1:52
  interested in the sciences, you know, went to college and again,
• 1:56
  was very interested in, in, in thinking about the, the biology
• 2:00
  and, and how, how do things develop the way they do.
• 2:03
  And, and, and eventually led to my PhD at Harvard looking at
• 2:10
  developmental biology. So why, you know, how do you go
• 2:13
  from a very simple cell, you know, structure to these
• 2:15
  complicated 3 dimensional beings with thousands of different cell
• 2:19
  types? And so understanding the
• 2:21
  processes and genetics involved was, was interesting.
• 2:24
  So I did that. And as I was finishing my PhD, I
• 2:32
  was sort of at that crossroads people reach, which is you want
• 2:34
  to go an academic route or you want to do an industry route or
• 2:37
  something different. And I felt that at the time I, I
• 2:42
  really enjoyed thinking about science and planning
• 2:45
  experiments. I really wasn't particularly
• 2:49
  enjoying the work on the bench. And so I actually after PhD went
• 2:56
  into strategy consulting because I wanted to learn the business
• 3:00
  side of science. So I did that for about 8 years,
• 3:04
  learned a tremendous amount about the business side from
• 3:09
  generic drugs all the way to new startups to big pharma and
• 3:13
  everything in between. And that was a great experience
• 3:17
  to help understand and learn more about the industry.
• 3:20
  I then left and went to Pfizer and in their R&D organization
• 3:27
  and it was a really interesting time to be there.
• 3:31
  Pfizer who just done their merger with Wyeth and we're
• 3:35
  trying to figure out what was the, you know, next thing, what
• 3:39
  was Pfizer going to be as, as, as this combined entity.
• 3:41
  So have the opportunity to help with that.
• 3:44
  And then spent a couple years in the UK in the, the first
• 3:48
  Cambridge, focused in on some of the cell and gene therapy assets
• 3:54
  that Pfizer had. And that was a fantastic
• 3:57
  experience to really broaden my depth and experience in, in, in
• 4:01
  the cell and gene space. And did that for several years.
• 4:06
  Came back to the US and decided I, I really wanted to double
• 4:10
  down in that space. So I left Pfizer and went to a a
• 4:12
  company here in the second Cambridge, Cambridge, MA called
• 4:16
  Siglon Therapeutics, which was a company looking at taking
• 4:21
  induced pluripotent stem cells, turning those into beta cells
• 4:25
  for type 1 diabetes. And so Sigilon was there about
• 4:28
  four years. We did a partnership with you
• 4:31
  like Lily in on diabetes and you know, really worked hard to
• 4:35
  bring this novel technology into the clinic and the company went
• 4:40
  public and soon thereafter I actually left and came to Arbor.
• 4:44
  Arbor is a next Gen. Gen. editing company and it, you
• 4:48
  know, as I've been in this space a long time, I've been a part of
• 4:52
  ARM, which is that, as you said, the cell and gene therapy
• 4:54
  industry group for since the beginning days, so almost 15
• 4:59
  years now. And I've always felt that, you
• 5:02
  know, cell therapy has a place and gene therapy has a place,
• 5:06
  but there's a tremendous amount of space in between that no one
• 5:10
  was covering. And I feel like gene editing has
• 5:12
  the opportunity to sort of fill that void where we can now
• 5:17
  actually fit and fundamentally impact the DNA to provide
• 5:24
  curative approaches in the right area of the gene.
• 5:28
  And so I think that is fundamentally a game changer.
• 5:32
  It also allows us to do to move cell therapy to in vivo.
• 5:37
  And so I think that, you know, gene editing really is starting
• 5:42
  to revolutionize the cell and gene therapy space will continue
• 5:45
  to. So that's sort of the the
• 5:47
  journey, I think biotech all along.
• 5:50
  I think there's nothing, I think there's nothing better than
• 5:53
  being in a career where you actually can impact the health
• 5:57
  of humankind, right? Like that's that's something
• 6:00
  that is always rewarding. And, you know, you hear stories
• 6:02
  from patients and you develop new drugs and you see the
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  impact. Like that's rewarding that that
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  makes it worth all the pain and suffering of, of, you know, they
• 6:11
  have to go through for drug development.
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  Yeah. And it's a similar, I mean most
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  people that I speak to have a very similar perspective on why
• 6:19
  they got into the industry. It's all about the patients.
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  So good. And can you share a little bit
• 6:24
  about the origin story behind the Biotechnologies and the
• 6:28
  inspiration behind its founding? Yeah.
• 6:30
  So Arbor was Co founded about 8 years ago by two pretty
• 6:36
  prominent scientist Feng Zhong who is a CRISPR pioneer from the
• 6:39
  Broad and MIT and David Walt who had Co founded aluminum among
• 6:45
  other companies. He is at the Visa Institute in
• 6:48
  Harvard and the two got together at the time recognizing that CAS
• 6:55
  9, which was the original CRISPR enzyme.
• 6:57
  The folks I can tell you and Editas and CRISPR use, but they
• 7:04
  recognize there are shortcomings that cast 9 is not going to be
• 7:08
  able to do everything that we need it to do.
• 7:11
  And so they got together, formed the company to really identify
• 7:16
  novel differentiated approaches to gene editing that allow us to
• 7:21
  really edit across the entire genome, as well as being able to
• 7:25
  do all kinds of editing so that we can effectively built a
• 7:29
  toolbox that allows us to to treat any genetic disease, no
• 7:32
  matter what the disease is. And so that was the ethos behind
• 7:36
  Arbor. I think as we look at what's
• 7:40
  been accomplished over that time, we now have a really
• 7:42
  robust toolbox that allows us to really tackle any genetic
• 7:47
  disease out there as a company, which I think is really
• 7:50
  important. So I think that was that's kind
• 7:52
  of the founding of the company and you know, I joined four
• 7:57
  years ago to take the toolbox and and and be very focused on
• 8:01
  translating that into therapeutics.
• 8:05
  Good, awesome. And Abu recently or recently
• 8:11
  announced that you guys entered the the clinic and then also
• 8:14
  secured 74 million in funding. Can you talk us through the lead
• 8:19
  candidate, the tech and how the funds will be used?
• 8:23
  Yeah, that's an important question for us.
• 8:25
  So the technology we have in the way we've focused our efforts,
• 8:32
  our current pipeline, we have five programs.
• 8:35
  Our lead program is in primary hyperoxide urea, which is a rare
• 8:40
  genetic disease. It's in the, the disease is in
• 8:44
  the liver, but it impacts the kidney.
• 8:45
  So children are diagnosed with kidney stones, which, you know,
• 8:52
  children do not get kidney stones, but in this case they do
• 8:55
  because there's a mutation where their bodies are unable to.
• 8:59
  They have an enzyme that's dysfunctional.
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  So they build up this oxalate which causes kidney stones and
• 9:05
  destroys the kidney. So these kids will have to have
• 9:09
  kidney transplants in their, you know, late teens, early 20s.
• 9:13
  So that's primary hyperoxide area.
• 9:15
  Our approach there is to go in and do a gene added in the liver
• 9:21
  to effectively eliminate the production of oxalate and form a
• 9:26
  different metabolite called glycolate, which is water
• 9:30
  soluble and can easily be cleared and so effectively
• 9:33
  eliminating the the disease state.
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  We hope and you know effectively in A1 and done approach.
• 9:39
  So treat patients once fix it throughout the liver and and
• 9:43
  they can live a more normal life.
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  So that's the the goal they program the data look quite
• 9:50
  compelling in both mice and non human primates.
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  And we got clearance to start the study in the United States
• 9:57
  and in in the UK and the trial is under way at this point.
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  So it's exciting to be able to take what will be the first non
• 10:10
  CAS 9 tested in vivo as well as we believe the first CRISPR
• 10:16
  approach to actually treat paediatric patients.
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  So a lot of firsts with this program that will be very
• 10:22
  exciting. So that's the lead program.
• 10:24
  Obviously the funds will be used to push that into the clinic and
• 10:27
  beyond. In addition behind that we have
• 10:30
  another rare pediatric liver disease using this time a
• 10:35
  different type of editing, it's called RT editing.
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  So we take a a nuclease and couple it to reverse
• 10:42
  transcriptase. And what that allows us to do is
• 10:45
  effectively rewrite sections of DNA.
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  So if you have a specific mutation you need to fix, you
• 10:53
  can go in with this technology and rewrite it.
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  And so again, focus on a rare liver indication where we can go
• 10:58
  in and fix the underlying mutation and hopefully provide
• 11:02
  significant benefits to these patients.
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  So that's the two programs in the liver.
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  And then we have a couple programs in the CNS.
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  You know, it's one of the benefits of our technology is
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  it's very small. So it allows us to move out of
• 11:18
  the liver. Currently, the rest of the
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  CRISPR companies are really in the liver because that's where
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  there's, you know, kind of have to be because their technology
• 11:27
  is large. So we can move out of the liver
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  and we really are intrigued by the central nervous system.
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  There's a a variety of genetic diseases there that have no
• 11:38
  effective treatment. So we are starting with a couple
• 11:41
  of programs targeting ALS, which is a a very deadly terrible
• 11:47
  disease for which there's effectively no real treatments
• 11:51
  today. And so being able to hopefully
• 11:53
  impact those patients positively would be fantastic.
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  So from a proceeds perspective, it's really about bringing 3 of
• 12:02
  the programs into the clinic. So PH1 being the lead program
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  and then two additional programs into the clinic.
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  Is there going to be the primary focus of the the fundraise we
• 12:11
  did? So you serve as a board member
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  and former Chairman of ARM, which you were speaking about
• 12:18
  before. Can you talk through your role
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  there and how some of those ongoing conversations that
• 12:23
  happened with the FDA as well? Yeah.
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  So I think it's as you know, chairman of ARM, it's been
• 12:32
  interesting to be involved with the organization.
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  So, so ARM is made-up of about I think 415 or so companies in
• 12:40
  cell therapy, gene therapy and gene editing.
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  And the primary goal is to really help advance the industry
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  and, and help in areas where there's, you know, any sort of
• 12:51
  bottlenecks or concerns. And so the three big areas I
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  think where ARM is able to impact and help the industry 1
• 12:57
  is in the regulatory side. So by identifying areas of
• 13:01
  interest that, you know, where we can help the regulatory
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  agencies educate them or partner on initiatives, that's really
• 13:10
  helpful. It's one area.
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  Another area is in really lobbying.
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  So they do a fly in every year into DC where there is, you
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  know, we'll go in with specific asks across the members of
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  Congress last year, there are a couple of asks. 1 is focused on
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  creating better reimbursement approaches for these one and
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  done approaches cause one and done treatments historically,
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  you know, didn't exist and suddenly we can cure patients.
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  The question is, how do you then get reimbursed?
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  Because the system set up for reimbursing, you know, every
• 13:48
  monthly you go get your prescription and it gets paid
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  for it. In this case, it's once and
• 13:52
  you're done. So how do we reimburse that and
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  and put in the right sort of framework to do that.
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  So there was some work on that that was done with the with CMMS
• 14:03
  particularly. And then importantly, ARM is a
• 14:08
  global organization. So similar to the work being
• 14:11
  done in the US is some of the work done in Europe and Asia on
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  trying to make sure that we help the regulators understand the
• 14:18
  unique opportunities and challenges with these types of
• 14:22
  therapeutics. And making sure that we put in
• 14:24
  place the appropriate frameworks to ensure patient safety.
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  But also make sure we eliminate hurdles on the regulatory side
• 14:32
  that may not be useful or you know, are not relevant to these
• 14:36
  types of therapies. So that's I think the primary,
• 14:39
  you know, some of the big missions of ARM, they also have
• 14:41
  one of the I think the premier meeting within our industry
• 14:45
  every year and it's called the meeting on the Mesa where I
• 14:48
  think about 2000 people typically go.
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  And it's a great opportunity to sort of understand what's going
• 14:55
  on in the sector and and how you know these therapies really
• 14:59
  changing patients lives today and will continue to do so in
• 15:02
  the future. Very good.
• 15:06
  And just a question back to you then.
• 15:09
  So you've been on both sides of the fence, big pharma, small
• 15:12
  biotech, your advisor for almost 8 years.
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  Talk us through the difference between being a a leader in a
• 15:18
  big pharma versus a small biotech in terms of how they
• 15:22
  think, just just the main differences.
• 15:27
  So that, that's a good question. So I think big pharma, you're
• 15:29
  looking at companies that are, you know, they're, they're
• 15:36
  large, they have a lot of different governances, there's a
• 15:40
  lot of committees and everything moves a little slower.
• 15:46
  And so you have to be able to navigate that system and being
• 15:50
  able to move quick is, is very challenging, I think.
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  And, and so, you know, when I moved over to biotech, I
• 15:57
  actually found it to be a kind of a breath of fresh air to be
• 16:01
  able to move so quickly to make decisions and move fast.
• 16:04
  The downside, I think to being in biotech is you don't have
• 16:07
  these large organizations to do things.
• 16:10
  So when I first joined signal on is that I think about the 10th
• 16:13
  employee, you know, we're like, OK, we don't have regulatory.
• 16:17
  I guess I'll own that. We don't have quality.
• 16:19
  Well, OK, I'll own that. So you have to wear a lot of
• 16:21
  different hats, which if one is, you know, if that's part of your
• 16:25
  DNA, you love that, then you will thrive in biotech.
• 16:28
  If you're used to having, you know, this huge organization
• 16:33
  rely on for all the expertise, then that's not a good fit for
• 16:36
  someone trans, you know, trying to transition from a big pharma.
• 16:40
  So very different. I think the other piece that I
• 16:43
  find interesting is in, in big pharma, you never know when
• 16:49
  there's going to be a reorg or a strategic refresh that's going
• 16:52
  to impact your, you know, your group or the work you're doing.
• 16:56
  And so you're kind of, you know, you just work along and someday
• 16:58
  someone somewhere besides, you know, makes a decision, your
• 17:01
  group disappears. I think in biotech you often
• 17:04
  have a better window because you, particularly in, you know,
• 17:07
  smaller companies, you know when the money runs out, you know
• 17:10
  what you have to accomplish. And it helps you to focus very
• 17:13
  much on what needs to be done. And if you, you know, if the
• 17:15
  science doesn't break or you don't accomplish what you're
• 17:17
  supposed to, then obviously you're, you know, you know, then
• 17:22
  your, your role may be impacted, but you have a much, I think you
• 17:26
  control your destiny more so I think in a small company.
• 17:31
  Yeah, I think that's a really good way of putting it.
• 17:34
  And I know one of the areas you wanted to talk about was about a
• 17:37
  Chinese scientist, Jankyu, who was jailed for three years after
• 17:42
  he he'd said he created the world's first gene edited
• 17:46
  babies. Give us your perspective
• 17:48
  perspective on how to think about the ethics of gene editing
• 17:52
  and whether we should gene edit embryos.
• 17:55
  Yeah. So if you think about South,
• 17:56
  gene editing is a powerful, powerful tool.
• 17:58
  It allows us to really fix problems or or mutations in the
• 18:03
  DNA. It has only been used in
• 18:06
  probably 200 patients, maybe 300 to date in vivo.
• 18:11
  And so the way it's done today, for example, our therapy will
• 18:15
  edit just the liver cells, which is where the disease is and that
• 18:20
  is appropriate. And I think particularly in
• 18:24
  these rare diseases that are extremely deadly and have
• 18:27
  terrible outcomes, that's where we should be focusing today.
• 18:32
  Someday, CRISPR use will be more widespread than other diseases.
• 18:36
  And, you know, eventually I think it will be utilized a lot
• 18:40
  like a vaccine, where you'll have your DNA sequence.
• 18:42
  They'll notice you've got, yeah, a propensity for Huntington's or
• 18:47
  Alzheimer's or whatever it may be, and you'll get it fixed
• 18:50
  before you have the disease. So that's all.
• 18:53
  That's all called somatic cell editing.
• 18:55
  So it's, you know, you're just editing cells of the body, not
• 18:58
  germ line. Germline editing is when you go
• 19:01
  in and you change an embryo or the DNA in a sperm or egg,
• 19:05
  fundamentally changing the DNA for all subsequent generations.
• 19:11
  Now the reason this is problematic and it's it's called
• 19:15
  heritable genome editing, is that a couple things.
• 19:21
  One, we are just learning how to make these things safe.
• 19:26
  You know, I think they are safe for use in, you know, specific
• 19:29
  organs today. I think we don't know and, and
• 19:34
  can't prove safety in editing an embryo because we don't, you
• 19:40
  know, it's you have to do like 3 generations or 4 generations in
• 19:44
  animals to confirm it's safe, which is a, you know, 20 year
• 19:46
  study that's, you know, not really feasible.
• 19:50
  And so I think particularly today, if you think about
• 19:55
  patients who have a disease and they don't want to pass it on,
• 19:59
  there are approaches today to allow you to not do that, that
• 20:03
  are not involved germline editing.
• 20:06
  And so I think the view that I have and I think most folks in
• 20:11
  this space have is that there is no need for germline editing,
• 20:18
  that we can accomplish what we need to in the somatic cell
• 20:21
  editing space. And that's where we should focus
• 20:23
  our efforts, I think, particularly as you get to the
• 20:26
  ethics of it. You know, I think the biggest
• 20:29
  concern is if you start editing the embryo is where do you stop,
• 20:33
  right. You start having designer
• 20:36
  babies. So, you know, and, and if and so
• 20:40
  that's really, I don't think the purpose of the technology and
• 20:43
  nor is that something that we should strive to do.
• 20:47
  And so I think particularly given all the unknowns on the
• 20:50
  science side and the technology side, I think we are best placed
• 20:54
  to not do any heritable genome editing in the near future.
• 21:00
  It's unfortunate that this one scientist in China did this and
• 21:05
  he did this on 2 patients or two babies.
• 21:09
  We don't know the outcomes because you know, Chinese
• 21:13
  government's been very quiet about it.
• 21:15
  But it is, I think ethically wrong and I think it's too early
• 21:18
  to begin doing this type of work.
• 21:20
  So fundamentally, I think we as an industry need to focus on on
• 21:26
  making drugs for patients with severe diseases where we can
• 21:30
  impact this particular disease in that patient, but not
• 21:34
  targeting in the germline. Also and then this is a question
• 21:41
  that we always finish with on the Bio Hub.
• 21:44
  If you were to have dinner with three people, past or present,
• 21:47
  who with the B&Y don't necessarily need to be biotech
• 21:51
  innovators all, although they can be if you like.
• 21:54
  Yeah, three people. Good question.
• 21:56
  I thought about this and I think the three I would do would
• 21:59
  actually be historical figures. One would be Isaac Newt, who I
• 22:04
  think is fascinating. When I lived in Cambridge, the
• 22:08
  first Cambridge, we'd often go to Westminster Abbey down in
• 22:12
  London where he's buried. And you know, I think he was, I
• 22:17
  was a Cambridge faculty member, I believe.
• 22:19
  And it's fascinating to see his life and, and the, the work he
• 22:22
  did on the science side and the amazing discoveries he did with
• 22:25
  effectively very rudimentary techniques and, and instruments
• 22:30
  in his control. The other one is Da Vinci, who I
• 22:33
  think is fascinating, right? Here's a guy who has done some
• 22:36
  of those famous paintings in the world, yet was probably one of
• 22:39
  the most prolific inventors that could see the future, right?
• 22:43
  He's he thought about flight. He thought about these things
• 22:45
  hundreds of years before it's feasible.
• 22:47
  And so it'd be fascinating to, you know, to sit down with him.
• 22:50
  And then the third one is Abraham Lincoln, who I think is
• 22:54
  a really good lesson in leadership in hard times.
• 22:57
  And I think there's a lot of good learnings I think that, you
• 23:01
  know, he's had and his experience would be fascinating.
• 23:03
  So those would be my 3 Abraham Lincoln, Leonardo da Vinci, and
• 23:07
  Isaac Newton because I think very different perspectives but
• 23:11
  fascinating characters. Yeah.
• 23:13
  But look, 3 terrific answers there and thanks so much for
• 23:16
  coming on and helping us out. I think it's been really
• 23:19
  interesting here in your perspective on, you know, ABBA,
• 23:23
  the the gene editing market. So thanks for so much for coming
• 23:26
  on. It's been a pleasure.
• 23:28
  Thank you, Tom. I appreciate it and it's a
• 23:30
  pleasure to have the conversation.
• 23:33
  Awesome.