Latest / The BioHub - by Avetix / Episode 205 - Paul Bresge - CEO of Ray Therapeutics

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Episode 205 - Paul Bresge - CEO of Ray Therapeutics · The BioHub - by Avetix

• 0:06
  So welcome back to the Biohub podcast.
• 0:08
  Today we're joined by super exciting guest, Paul Brezka of
• 0:12
  Ray Therapeutics. Paul, pleasure to have you on.
• 0:15
  How are you doing? Great.
• 0:17
  Thank you so much for having me. I'm doing great.
• 0:19
  Thank you so much. How are you doing?
• 0:21
  Good. Yeah, Yeah, No, all good.
• 0:23
  We're looking forward to this one.
• 0:26
  Thank you. I think it's always useful to
• 0:28
  start off with Paul. I know we're going to get into
• 0:31
  the technicalities about the, the platform and the technology
• 0:34
  and, and the team as well, Ray. But I think it's always nice,
• 0:38
  particularly with yourself to start off with a little bit of
• 0:41
  background about the guest for the audience.
• 0:43
  And yeah, we interview a lot of CE OS and a lot of companies,
• 0:47
  right? And then everyone has everyone
• 0:49
  route into biotech. I guess you have a pretty unique
• 0:54
  story behind that as well. Would, would you mind going back
• 0:57
  and sharing a little bit about, yeah, what, what led you into
• 1:00
  the biotech world and obviously founding two companies now sort
• 1:05
  of what prompted that? Of course.
• 1:08
  Yeah, I know. Thank you for the opportunity.
• 1:11
  So yeah, I had probably, you know, a less traditional path
• 1:14
  into biotech. I had the good fortune of
• 1:17
  actually starting off my career in the very early days in
• 1:21
  generic pharmaceuticals, which certainly was a good, you know,
• 1:25
  grounding, you know, of, of, of that industry in particular.
• 1:29
  And then moved into contract manufacturing for pharma, which
• 1:32
  again, you know, not knowing at the time it would end up, you
• 1:37
  know, becoming very useful, you know, many, many years later.
• 1:41
  I did get out of the industry for a long time.
• 1:43
  I went, I did a whole bunch of really fun entrepreneurial
• 1:46
  things, got heavily into real estate, real estate development,
• 1:50
  some operating companies, you know, was having a lot of fun
• 1:55
  with my career. And then in 2010, my middle
• 1:58
  daughter, her name is Tamar, she had just turned 15 at the time,
• 2:04
  was diagnosed with rhinitis pigmentosa.
• 2:07
  We were told by the chief ophthalmologist to Toronto Sick
• 2:10
  Kids Hospital that she was going blind, that there was nothing
• 2:13
  that could be done to save her vision.
• 2:16
  And we were basically sent on our way with a handbook to the
• 2:19
  Canadian National Institute for the Blind.
• 2:23
  That day we made a promise to one another.
• 2:26
  The first thing that I did when I got home, obviously, was
• 2:29
  Google the disease and learn much more on Google than I did,
• 2:32
  you know, we did from the doctor.
• 2:35
  And I went upstairs to her room. She was opening up her laptop.
• 2:39
  And I said, you make me a promise and I'll make you one in
• 2:41
  return. Your promise is to go on and do
• 2:44
  everything that you want to do with your life.
• 2:47
  Because that doctor had actually very inappropriately told her at
• 2:51
  such a young age that she should consider what she was going to
• 2:54
  study and what she was going to do with her life, given the fact
• 2:56
  that she had a blinding disease. And I said to her, you know, I
• 3:00
  want you to forget about what that doctor said.
• 3:02
  Do not Google the name of your disease.
• 3:04
  You just go on with your life. Do whatever you imagined you
• 3:07
  would want to do with your life and let mom and I essentially
• 3:10
  worry about your disease. That took me, you know, very
• 3:14
  heavily into a research phase where I was trying to find a
• 3:17
  program that was promising and recognize his pigmentosa.
• 3:21
  This is really before the days of cell and gene therapy.
• 3:23
  In fact, I remember, you know, very early on speaking to AVC
• 3:27
  about a cell therapy program and this one, one of the top VCs in
• 3:31
  the world called voodoo medicine.
• 3:34
  So it was when, you know, cell therapy was really at its
• 3:36
  infancy. But I found this program out of
• 3:39
  University of California, Irvine, a husband and wife team,
• 3:43
  really brilliant scientists and they had what I considered very,
• 3:46
  very exciting proof of concept early, you know, in, in rodents
• 3:53
  essentially. But I felt that it, it had great
• 3:56
  promise to, you know, become a drug.
• 3:59
  And that led to the formation of a company called J Site, which I
• 4:03
  got involved in in 2010 and took all, took that all the way
• 4:07
  through to late stage clinic and eventually a licensing deal with
• 4:12
  a pharma company in 2020. So that was my foray back into
• 4:18
  the space that particular program and it still has an
• 4:23
  enormous amount of promise. In fact, they're in late stage
• 4:26
  clinical trials still is really designed to slow down the
• 4:31
  progression of disease and maybe to have some efficacy in
• 4:36
  regaining vision. But the concept of that program
• 4:40
  requires that patients still have photoreceptors.
• 4:42
  And what happens over a period of time in these degenerative
• 4:46
  diseases is that patients actually lose their
• 4:48
  photoreceptors. So thinking, you know, about the
• 4:52
  10 year period between 2010 and 2020 and given the fact that my
• 4:58
  daughter's, you know, disease had obviously progressed quite
• 5:01
  substantially in that time, I wanted to get into something
• 5:04
  that was targeted for more late stage patients.
• 5:08
  And that's where, you know, I came across a group that were,
• 5:12
  you know, interested in forming Rate Therapeutics around some
• 5:15
  really exciting technology targeting late stage patients
• 5:19
  who've already lost their photoreceptors and very
• 5:22
  importantly in both programs able to treat patients
• 5:30
  irrespective of the underlying genetic mutation.
• 5:35
  So I hope there wasn't too much detail, but that certainly is,
• 5:39
  you know, how I got to where I am today with a really exciting
• 5:43
  programme with with Ray Therapeutics.
• 5:45
  Yeah, I mean, it's an awesome why, right that for sure.
• 5:49
  I know everyone has a different purpose, you know, behind
• 5:52
  getting into bias, but that's yeah, that really hits home for
• 5:56
  sure. How did the how did the rate
• 5:59
  opportunity come about? Did you just get introduced to
• 6:02
  to the founding team, the the scientists or?
• 6:06
  No, I I had really been looking at optogenetics for a long time.
• 6:10
  Actually, I've been following the space, as you can imagine, I
• 6:12
  followed absolutely everything in the space.
• 6:14
  I think I'm the one, you know, very few CE OS that I champion
• 6:19
  competition, you know, as a parent and as ACEO, actually
• 6:22
  anything, you know, successful in the space is, you know,
• 6:25
  success for the industry and for patients, you know, at large.
• 6:28
  And there are so many patients with so many different blinding
• 6:31
  diseases that I'm, you know, a huge champion of of any work
• 6:36
  that's being done. So I've been following up to
• 6:38
  genetics and I, I was always really interested in the science
• 6:42
  and proof of concept I think had already been established pretty
• 6:45
  early that it works for patients with very late stage disease.
• 6:49
  But the earlier stage programs required that patients wear
• 6:55
  light enhancing goggles in order to activate the protein which
• 7:00
  gives them light. And while that's really
• 7:03
  promising for patients and, you know, I think this had pretty
• 7:07
  remarkable results to me, the concept of trying to get a novel
• 7:15
  therapeutic combined with a novel device through regulatory
• 7:20
  and commercial is just, you know, hugely, you know, heavier
• 7:25
  or less than getting a therapeutic through.
• 7:27
  So that was, to me a stumbling block when I saw the data that
• 7:33
  formed Ray Therapeutics, which uses essentially the most light
• 7:37
  sensitive protein that's found in nature.
• 7:39
  And then that protein has been highly bioengineered for human
• 7:43
  vision restoration. For the first time, looking at
• 7:47
  the animal data, it wasn't even a question for me.
• 7:49
  I was just like, absolutely I'm in and was very grateful to
• 7:53
  become part of the founding team.
• 7:55
  Yeah, nice. I was going to say what what
• 7:57
  sort of prompted you to say, you know, because it was 10 years at
• 8:00
  J site, right. So long, long, long time.
• 8:05
  I guess it's that initial data that you saw which you know
• 8:08
  you're all in. Yeah, that and as I mentioned,
• 8:11
  you know, the the shift to targeting therapies for later
• 8:17
  stage disease just given the amount of, you know, time that
• 8:20
  had passed since my daughter's diagnosis and bringing Jason to
• 8:25
  late stage. Yeah, that makes sense.
• 8:29
  Cool. So let's let's get into the the
• 8:31
  Ray story and the Ray platform, if we can of.
• 8:35
  Course, obviously. You guys are are pretty
• 8:38
  different in in the field. Do you want to explain quickly
• 8:40
  why that is and give a high level of view of of the
• 8:43
  technology? Sure.
• 8:46
  I've essentially done that to some degree or maybe to a large
• 8:49
  degree and that is that we have taken as I mentioned the most
• 8:52
  light sensitive protein found in nature.
• 8:54
  So there's no need for these, you know, additional light
• 8:56
  enhancing goggles and then for the first time bioengineered
• 9:02
  that protein for human vision restoration.
• 9:04
  So the earlier generations, again, not as like sensitive
• 9:07
  owls is like sensitive enough essentially at 1 E 13 where
• 9:12
  people just have to open their eyes at St. lighting at night
• 9:14
  and the protein is activated. And then the fact that it's
• 9:18
  bioengineered, it will create that hypothesis that it will
• 9:22
  create functional vision as opposed to merely, you know,
• 9:26
  additional light, which sort of is meaningful.
• 9:28
  But when you think about how complex vision is, the fact that
• 9:31
  this protein has been optimized for those complexities should
• 9:35
  render, you know, very exciting results.
• 9:38
  And that's exactly what we're seeing in our phase one study.
• 9:41
  I could not be more encouraged, could not be happier with where
• 9:45
  we are AT and how the science has translated to human
• 9:51
  efficacy. I think we've seen a lot of, you
• 9:53
  know, mice and rats and different animal models being
• 9:56
  cured in early stage free clinical work, but that does not
• 10:01
  usually, it actually does not translate to the same kind of
• 10:04
  efficacy in humans. We are seeing that efficacy and
• 10:08
  we're, you know, just absolutely so encouraged by that, so much
• 10:14
  so that although we've completed phase one study, only 9
• 10:18
  patients, the data is robust enough that it informs a Phase
• 10:24
  2-3 pivotal design and we'll be entering that study in the next
• 10:28
  couple of months. Yeah, that's awesome.
• 10:31
  And that that data has also provided the basis for the the
• 10:34
  prime and the ARMAT designations that you guys have correct got
• 10:37
  right. Correct.
• 10:38
  Yes, Thank you for mentioning that.
• 10:40
  We have not done a data release yet.
• 10:43
  We will at your Retina which is a very big conference coming up
• 10:47
  in October and then AAO another big conference coming up in
• 10:50
  October and then I think the next one is the for Retina
• 10:54
  conference in December. That's where we will be
• 10:57
  releasing data for the first time.
• 10:59
  That correct. Yes, receiving Prime and Armat
• 11:03
  designation validates our excitement that the data is
• 11:06
  robust enough to earn, you know, those very high bars that are
• 11:10
  required for those two designations.
• 11:13
  I was going to say, I mean, most people tuning in will will know
• 11:17
  just how high a bar it is to, to receive that those accolades.
• 11:21
  But yeah, super impressive and nice.
• 11:26
  You mentioned the two ongoing clinical trials and Vision
• 11:29
  Aurora. Do you want to talk about you've
• 11:32
  got 2 platforms, right to sort of different?
• 11:35
  Yes, we do. So this year we'll actually be
• 11:37
  in four clinical studies, which is you know why you might notice
• 11:43
  that there's quite a quite a substantial amount of growth
• 11:45
  that you know the the company is posting on LinkedIn as we bring
• 11:48
  in new hires. So we will be completing this,
• 11:51
  you know, phase one study in RP and we continue to bring
• 11:54
  patients in. In fact, the patient was in just
• 11:56
  recently for their 18 month visit.
• 11:59
  Uh, and we continue to see the, you know, the sustainability of
• 12:03
  the, uh, efficacy, which again is, you know, so exciting.
• 12:06
  Uh, and as mentioned, we'll be moving into a Phase 2-3 study
• 12:10
  this year in RP. That's for the ORTXO 1/5
• 12:13
  program. Now that program targets the
• 12:16
  retinal ganglion cells because it's essentially patients with
• 12:20
  inherited retinal diseases other than star guards.
• 12:23
  That's really the the last cell that's remaining in the retina.
• 12:28
  So we have to make sure that we're targeting those cells and
• 12:32
  that's what our RTXO 1/5 program does.
• 12:35
  We have another program that's in clinic already where we
• 12:37
  started treating patients with star guards disease.
• 12:40
  Now the difference with star guards and geographic atrophy is
• 12:43
  that patients with those diseases in late stage, they
• 12:48
  still retain their bipolar cells, which is more, those
• 12:51
  cells are more upstream and there's more of them.
• 12:54
  So obviously we want to give the patients literally the best shot
• 12:57
  on goal. So the RTX 02/1 program, we have
• 13:01
  a proprietary on bipolar specific promoter.
• 13:05
  So the protein goes to those bipolar cells and that's, you
• 13:10
  know, that's already in clinic with star guards.
• 13:13
  As I mentioned, we have an open Ind in geographic atrophy and
• 13:17
  we'll be dosing patients this year with geographic atrophy as
• 13:20
  well. So we'll be in, you know, 3
• 13:22
  early stage programs, one late stage program.
• 13:25
  And then most importantly, and I'm sure you know you, you're so
• 13:29
  well versed in the industry that you know that CMC manufacturing
• 13:32
  is often the Achilles heel and gene therapy.
• 13:35
  I'm pleased to say that if anything our CMC is ahead of
• 13:40
  clinic where we have before we dosed a single patient in, in
• 13:45
  both programs we made sure that we had a product that was
• 13:50
  manufactured at commercial scale using a commercial process.
• 13:55
  So we're already in very late phase manufacturing, preparing
• 13:59
  for commercial readiness on the CMC side so that there's no
• 14:02
  delay in getting this, these really important therapies to
• 14:07
  patients. Uh, where, you know, often
• 14:09
  there's this, this bridge of the oldies phase, uh, clinical
• 14:14
  material to late phase commercial material.
• 14:17
  We've eliminated that, uh, you know, entire bridge.
• 14:21
  Yeah, it's the right thing to invest in that early.
• 14:23
  It'll cost you later on if if you don't.
• 14:26
  Well that so I am so grateful to the investors that saw potential
• 14:31
  in our program with our seed round in you know 2021 for
• 14:35
  Biocapital LED that seed round. In 2023 we did $100 million
• 14:41
  round that was led by Novo. We have Deerfield, Norwest,
• 14:45
  Platinus for bio and work Ventures in that round.
• 14:49
  And then recently we closed the Series B rounded by Janus.
• 14:53
  We have Franklin Templeton, we have Marshall Ways, we have
• 14:56
  Inverse, we have Adage. So, you know, really strong
• 15:01
  group of investors between the Series A and the Series B and
• 15:04
  again, just lots of gratitude for that.
• 15:07
  Yeah, absolutely. I I was going to touch on the
• 15:09
  funding. Obviously the, you know, you
• 15:12
  need the platform, you need the technology, you also need the
• 15:14
  team, but none of it happens with without the fund, right.
• 15:18
  So how did you find raising the, the B round in, in the market?
• 15:22
  Obviously it's a bit of a mixed bag, right.
• 15:25
  And some people you speak to really positive, some people
• 15:27
  less so. Yeah, I think it's getting, you
• 15:31
  know, I'd never say easier because it's never easy, but I
• 15:34
  think that it certainly is, you know, opening up more and more
• 15:38
  even since we did the race, which closed, you know, in March
• 15:42
  of this year. But we, you know, we got a lot
• 15:47
  of track traction, you know, very quickly and you know, with
• 15:50
  such a strong lead like Janice and the fact that all of our
• 15:53
  Series A investors wanted wanted to participated, you know, in
• 15:57
  pro rata or super pro rata in the round also gave the other
• 16:00
  investors confidence. So between the series and the
• 16:05
  Series B investors, the challenge was to keep it as
• 16:09
  after 125 and not go higher, which is a very, very nice
• 16:13
  problem to have. I.
• 16:14
  Was going to say. Yeah.
• 16:17
  So for us, it was, you know, it was obviously very fruitful, but
• 16:22
  also, you know, just a great process.
• 16:26
  Yeah, awesome. I mean, there's some some pretty
• 16:29
  good names to have on that ticket for sure.
• 16:33
  Nice. Awesome.
• 16:33
  Well, look, one thing I did want to touch on, Paul, I mean, you,
• 16:38
  you touched on it earlier team, how important it is.
• 16:42
  I know when we did the prep for this episode, it was something
• 16:45
  that you were keen to, to highlight, you know, just how
• 16:48
  important getting the right people in and around he has, has
• 16:52
  been. You gave a key point in that, in
• 16:56
  that you said that you test for patient centricity when you're
• 17:01
  interviewing. And I know obviously being
• 17:03
  patient centric is super important to you naturally.
• 17:06
  You know, we touched on it at the start of the the interview.
• 17:10
  How have you tested for that? As you've grown the
• 17:13
  organization, I guess how do you continue to test for it because
• 17:17
  people have all sorts of different reasons for working
• 17:19
  right and, and working in biotech.
• 17:20
  Yeah. How do you go about that?
• 17:24
  Yeah, I know it's a great question and, you know, thank
• 17:28
  you for mentioning it because it's very, very important when
• 17:31
  I'm on the, you know, topic of gratitude to the investors.
• 17:34
  I'm also so grateful for the team that has really, you know,
• 17:38
  it takes a village literally. And you know, I have been so
• 17:41
  fortunate to have such a strong C-Suite team and also such a
• 17:46
  strong, uh, you know, clinical team, CMC team, you know, really
• 17:52
  working day and night to move our programs forward.
• 17:57
  I think people are highly motivated by the patient focus
• 18:02
  When I'm interviewing people and, and I interview absolutely
• 18:06
  everybody. Even now that we're in a massive
• 18:08
  hiring Phase, I always make sure that I have at least the last
• 18:11
  interview because I think it's as important for the people, you
• 18:16
  know, who are joining the companies, you hear from the CEO
• 18:19
  as it is. It's a big decision for both
• 18:21
  people. So I always want them to really
• 18:24
  understand that every single decision that we make at Rave
• 18:28
  Therapeutics, we have to ask ourselves a question, you know,
• 18:32
  is this the best decision for the patient?
• 18:36
  And I think that drives absolutely, you know, anything
• 18:40
  and everything that we do, for example, I think we've done
• 18:45
  something that's very different to not I think it's, it is just
• 18:49
  unequivocally very different to anything that any other retina
• 18:53
  program has done as it relates to endpoint testing because this
• 18:57
  is a very challenging patient population.
• 19:00
  It's a heterogeneous population. These patients are essentially
• 19:05
  blind, you know, legally blind. And a lot of them, you know,
• 19:08
  with very advanced blindness. The retina clinics, and we work
• 19:13
  with the top retina clinics, you know, in the world, they don't
• 19:16
  have the expertise in how to test blind patients.
• 19:18
  They sometimes don't have the test.
• 19:20
  So what we did very prospectively, and this comes
• 19:23
  back to my gratitude for the fact we had so much funding, was
• 19:27
  we built a center that we called the Vision Research and
• 19:30
  Assessment Institute. And we did that two years before
• 19:33
  we dosed a patient and we staffed it with the country's
• 19:37
  top low vision experts. And we ran Natural History
• 19:41
  studies in different disease indications, primarily NRP,
• 19:45
  because that was our lead program to understand what
• 19:49
  endpoints are appropriate and more importantly, what endpoints
• 19:52
  are not appropriate. So making sure that we were
• 19:54
  getting away from anchor bias, which is, you know, I think just
• 19:59
  probably across all, you know, fields.
• 20:01
  But in ophthalmology, it's very much, you know, 3 lines of
• 20:05
  change or 15 letters or you know, if we go to the spark
• 20:08
  mobility maze. We wanted to make sure that we
• 20:11
  were testing all functional vision and not just limiting
• 20:16
  ourselves. So that Natural History study
• 20:18
  really allowed us to understand endpoints and then also to
• 20:21
  reduce variability because that's also been a problem in
• 20:25
  retina in that because again, it's so heterogeneous, patients
• 20:29
  have good days and bad days that sometimes there's a lot of noise
• 20:32
  in the data. But when you have experts doing
• 20:35
  it and they're doing it over and over and they really understand
• 20:38
  the patient population, you're able to get more reliable and
• 20:42
  more, I would say, relevant data.
• 20:46
  So that's been, you know, very exciting for the company.
• 20:49
  So I think going back to your question, I think when
• 20:52
  candidates are looking, you know, at the company and they
• 20:54
  see that we really authentically do everything with the patient
• 20:59
  in mind. I it's, it's contagious.
• 21:02
  And you know, we hear that at our all hands meetings.
• 21:05
  We had one very recently and we're always opening up the, the
• 21:09
  discussion. I always do.
• 21:10
  Does anybody have any great ideas for us?
• 21:12
  And one of our, you know, brilliant people in CMC said,
• 21:16
  you know, I've never met anybody with late stage blindness.
• 21:20
  Could we have a patient or could we have somebody, you know, with
• 21:25
  the disease that we're targeting come in just so that we can
• 21:28
  actually have somebody in our minds as opposed to just be
• 21:30
  patients as a concept? Can we meet someone?
• 21:33
  And so we've organized for a brilliant, brilliant speaker.
• 21:36
  Her name is Christian McDonald. She has very late stage RP.
• 21:41
  So she's coming to our office on July 27th and she's meeting with
• 21:44
  all of our staff and she'll talk about her experience and she'll
• 21:47
  also talk about why it's so important that we're doing the
• 21:50
  work that we're doing. So I, I think we've, you know,
• 21:55
  again, it's the authenticity of the patient that I think has
• 22:00
  already been built into the culture.
• 22:02
  Yeah. And I think the authenticity
• 22:04
  comes across when when speaking to you, Paul as as well.
• 22:07
  And ultimately. Culture comes from leadership,
• 22:11
  right? If if leadership aren't living
• 22:12
  it, then the rest of the organization, yeah.
• 22:16
  What's on them to, to do so? Yeah, no, but look, thanks for
• 22:21
  coming on and sharing the story. I can't can't wait till you Etna
• 22:25
  and seeing the first data. It would be amazing.
• 22:29
  So yeah, look forward to that. And yeah, we'll have to get you
• 22:32
  back on maybe sometime in early New Year and and talk a bit more
• 22:36
  about that and what it means moving forward.
• 22:38
  I would love to again, thank you so much for the opportunity.
• 22:41
  Thank you for the great questions and really appreciate
• 22:44
  that you gave me the chance to come out and have this
• 22:46
  discussion. Ah, pleasure.