Latest / The BioHub - by Avetix / Episode 156 - Rafiq Hasan - CEO of Complement Therapeutics

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Episode 156 - Rafiq Hasan - CEO of Complement Therapeutics · The BioHub - by Avetix

• 0:06
  Another live episode of the Biohub podcast.
• 0:08
  Today we're joined at the Translation and Innovation Hub
• 0:11
  in White City by Rafiq Kassam from Compliment Therapeutics.
• 0:15
  Thanks for coming on. Good to see.
• 0:16
  You again Thanks, Callum. Great to be here.
• 0:18
  Sure. I mean, pretty exciting
• 0:20
  announcement yesterday, so very good timing.
• 0:23
  Absolutely. Yes, Yeah, absolutely.
• 0:25
  Yeah, I know it's a great day. You know, I think we were very
• 0:27
  pleased to announce that we had dosed our first patient in our
• 0:31
  interventional trial. So we're off and running, which
• 0:34
  is great. And now we're looking forward to
• 0:36
  really driving enrollment and seeing some of that data.
• 0:39
  Yeah, for sure. And I guess just to start off,
• 0:42
  yeah, with complement technologies from the University
• 0:46
  of Manchester, correct, HQ Munich.
• 0:50
  Yes. He is Stevenage.
• 0:52
  Yeah, yeah, focused through all that and yeah, no, you know, I
• 0:54
  think it was, you know, like you say, we dialed the clock back
• 0:58
  4-5 years now back in 2021, you know, great science from our
• 1:02
  founders. I think that stimulated some
• 1:05
  investment from, you know, initially from by generation
• 1:08
  ventures closely followed by phobia, you know, really great
• 1:12
  venture funds in Europe. And I think, you know, that
• 1:15
  really solidified that this looks really quite promising.
• 1:19
  You know, I think the founders had and and their background was
• 1:21
  very much in complement in ophthalmology.
• 1:24
  So you know, I think that's really why that initial focus is
• 1:28
  in that indication certainly focused on the complement
• 1:31
  system. And you know, at that time where
• 1:35
  as as those investors were getting involved, I think they
• 1:39
  were looking for individuals with relevant sort of subject
• 1:42
  matter expertise. And at that time, you know, I
• 1:45
  was approached through some some networks that, you know, I
• 1:48
  developed certainly in historically in my career at
• 1:51
  Bayer. And then, you know, prior to
• 1:53
  that at Novartis. And, and was asked, you know,
• 1:55
  would I be interested initially actually in joining the board
• 1:59
  in, in chairing the company. And you know, I think having
• 2:02
  looked at the data, having looked at some of the science,
• 2:05
  you know, that was certainly very impressive.
• 2:07
  And I felt, yeah, it looks like a really great opportunity.
• 2:10
  So actually initially I joined as chair of the company and then
• 2:13
  about sort of 6-8, seven months later, I was asked, you know,
• 2:16
  would I be interested in flipping over to be the CEO and
• 2:20
  really driving the business. And, and I think with the
• 2:22
  commitment from those investors and then subsequently raising
• 2:26
  the Series A round, you know, it's been a fantastic journey,
• 2:29
  You know, I think and really building the team, really
• 2:32
  working on the innovative science and, and seeing that
• 2:35
  come to fruition, you know, I think that's the real satisfying
• 2:38
  pieces. I think when you start out, you
• 2:40
  know, it's really just a concept and then building an asset,
• 2:43
  taking it through preclinical, going through the regulatory
• 2:46
  reviews and now starting to treat patients, you know, is
• 2:50
  really satisfying. So it's been a, it's been a
• 2:52
  fantastic journey. Yeah, and quite a quick journey
• 2:55
  in the grand. Scheme, absolutely, absolutely.
• 2:57
  You know, I think, I think that's testament to the team
• 2:59
  that we have. You know, we have just fantastic
• 3:01
  experts in the space who really know what they're doing.
• 3:05
  And, and I think like you say, having done it in sort of four,
• 3:08
  4 1/2 years, particularly for a gene therapy where we know there
• 3:12
  are challenges. You know, manufacturing can be
• 3:14
  challenging. And you know, with, with all
• 3:16
  those things, it sounds great. But of course there's always
• 3:19
  some detours and bumps in the road.
• 3:21
  But I think what what really resonates with me is having the
• 3:24
  right people who can actually address those challenges.
• 3:28
  You know, I think science is great and, you know, the
• 3:30
  technology is great, but actually having the right team
• 3:34
  who know how to navigate those challenges and, and really bring
• 3:37
  that to fruition is so important.
• 3:39
  Yeah. Translating that into patients
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  is another. Thing.
• 3:42
  Yeah, absolutely. Absolutely.
• 3:43
  Most of the team are split between here and.
• 3:46
  That's right. Yeah.
• 3:47
  So, so I think, you know, initially we were actually
• 3:49
  starting out here as you know, the, the, the technology came
• 3:53
  out of the University of Manchester, which is great.
• 3:56
  I think at the right at the beginning, there was almost like
• 3:58
  a sort of PO Box in Manchester. We then started to build a team.
• 4:02
  And I think, you know, being here on this Imperial College
• 4:05
  campus, I think gives us access to the right type of talent,
• 4:09
  gives us exposure as well. And then like you say, we then
• 4:13
  built the lab in Stevenage. And again I think having that
• 4:16
  internal capability where even on a small scale we can do some
• 4:20
  manufacturing, but then we can do a lot of in vitro work, cell
• 4:23
  based assays and what have you in Stevenage.
• 4:26
  And then having the Munich sort of base as well.
• 4:29
  And actually we have AUS subsidiary as well.
• 4:31
  So because our CSO is based in the US.
• 4:34
  So I think having actually cross geographical presence optimizes
• 4:39
  because I think we're then able to bring people on really almost
• 4:43
  irrespective of where they're located.
• 4:45
  Yeah. And I think particularly when we
• 4:47
  think about the US, we've just started our interventional
• 4:51
  trial. Our first patient dose was in
• 4:53
  the US yeah, you know, if we then wanted to build further
• 4:57
  presence in the US and and that's likelihood the the the
• 5:00
  sort of direction of travel. So when things go exactly, you
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  know, we we have that presence and and we're able to add
• 5:05
  people, you know, fairly easily. So, so I think, you know, the
• 5:09
  nature of and, and I think post pandemic, you know, remote
• 5:12
  working, that sort of hybrid model works pretty well.
• 5:16
  And and I think actually it then allows us to hire the right
• 5:20
  people and you're not too hung up about location or you're not
• 5:24
  thinking about also having to relocate people.
• 5:27
  Particularly when you're in an area like gene therapy, I know
• 5:30
  it's the lead program is gene therapy and not every program
• 5:33
  necessarily will be. Absolutely.
• 5:35
  Yeah, in such a relatively tight space, that's why that's exactly
• 5:39
  important. Do you mind just giving a high
• 5:41
  level of on the science? Sure.
• 5:43
  For my sake. No, no.
• 5:45
  Well, you know, I always say the complement system is quite
• 5:49
  complicated. Yeah.
• 5:50
  And and, you know, it's, it's basically part of our innate
• 5:53
  immune system and therefore protects us, protects us from
• 5:56
  viral infections, from bacteria, from infections, from external
• 6:00
  challenge. But I think what we see is and
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  and this is across several disease areas, when it sort of
• 6:07
  becomes dysregulated, you get diseases that drive in.
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  You know, inflammation is often a key hallmark of dysregulation
• 6:15
  of the complement system. And I think, you know, what we
• 6:18
  know from historical data is people with this type of eye
• 6:22
  disease, it's a type of age-related macular degeneration
• 6:25
  called geographic atrophy, a late form of that.
• 6:28
  Certainly all of this sort of histopathological data and other
• 6:32
  data suggests that number one, it's characterized by
• 6:35
  inflammation and #2 what we see is deposition of complement
• 6:39
  proteins in the lesions that are characteristic of this disease.
• 6:44
  So I think for, for several years, for decades, there's been
• 6:47
  a focus on modulating the complement system.
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  And I think really in the last 10 years or so, we've seen
• 6:53
  really significant progress there that actually down
• 6:57
  regulating the complement system can result in, in slowing of
• 7:01
  disease progression. And really we're building on
• 7:04
  that science. So I think, you know, we, we
• 7:06
  see, for example, in the US, we have two approved products that
• 7:09
  are frequent injections in the eye that have shown that they
• 7:13
  can slow the disease. And, and one of the, the
• 7:16
  learnings from my own career was actually injections in the eye
• 7:19
  of, you know, patients don't really mind them.
• 7:21
  We are we to us that feels like quite, quite a, you know,
• 7:25
  invasive approach. But actually coming back
• 7:28
  frequently for the injections is often the bigger challenge.
• 7:32
  Got you. And as a consequence, a gene
• 7:34
  therapy approach makes a lot of sense.
• 7:36
  You know that potential that you do a one time administration and
• 7:40
  you see durability of effect I think is particularly important.
• 7:45
  And so the way we're approaching this is we have a protein that
• 7:49
  is made from our gene therapy. So essentially we're doing a
• 7:52
  subretinal injection. We think that's important
• 7:54
  because that's really where the disease activity is occurring
• 7:58
  and the the the cells of the eye, the RPE cells, the retinal
• 8:01
  pigment epithelium cells produce a regulatory protein that
• 8:06
  basically downgrades ocular inflammation through down
• 8:10
  regulation of complement activity.
• 8:13
  Nice, understood. And with the enrollment of the
• 8:17
  Phase 1 two study, yeah, I know you probably discussed this in
• 8:21
  Lisbon a little bit as well, design study to include some
• 8:23
  like maybe not different endpoints.
• 8:26
  No, you're not absolutely. I think that is is, you know it
• 8:29
  is quite a topical issue in the world of GA and ophthalmology is
• 8:33
  endpoints. Yeah.
• 8:35
  So if we look at the proof products I mentioned, what
• 8:38
  they've shown is that they can slow disease progression, so
• 8:42
  reducing the growth of these lesions in the back of the eye.
• 8:46
  But as you can imagine, patients, payers, others say,
• 8:50
  show me how that preserves vision, What's the functional
• 8:54
  impact of slowing that disease progression.
• 8:57
  And I think that's where we've struggled because this is a
• 9:00
  slowly progressing disease and you know, ideally you'd want to
• 9:04
  follow patients for five years or longer to say actually
• 9:07
  slowing that lesion progression translates into a functional
• 9:11
  benefit. So as a consequence, I think
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  taking learnings from some of these other programs, there's
• 9:18
  been a particular focus on novel endpoints that may show you a
• 9:23
  signal of efficacy earlier, but then also they correlate pretty
• 9:27
  well with functional outcomes. So our focus is really looking
• 9:31
  at really two novel endpoints alongside others.
• 9:33
  We're doing the standard pieces as well, but something called
• 9:37
  ellipsoid zone attenuation, quite technical, but essentially
• 9:40
  it's, it's a line on the imaging on the Oct that basically fades
• 9:45
  over time as the disease progresses.
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  Got you. And that's an indicator of
• 9:49
  photoreceptor health the the cells that really allow us to
• 9:52
  see. So as that, if you can preserve
• 9:55
  that line, we know that that would likely result in proving,
• 10:00
  you know, preservation of sight. And then on top of that, there
• 10:04
  are other ways in which you can measure function and something
• 10:07
  called micro perimetry where you give patients a clicker shine
• 10:11
  dots of light on different parts of the retina and they basically
• 10:14
  click if they can see that. And again, we've, we've got a
• 10:18
  sort of novel approach to that, something called focal micro
• 10:21
  perimetry where we're really focusing on the, on the area
• 10:24
  around the lesion, really the photoreceptors that are most at
• 10:28
  risk. And, and again, there's some
• 10:30
  nice data from other analysis that have been done often post
• 10:35
  hoc. So we're doing that
• 10:36
  prospectively, which we think is particularly exciting.
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  And I think, you know, as a consequence, you know, we're,
• 10:42
  we're confident based on the preclinical profile of our asset
• 10:46
  that we have that potential to see something fairly early on in
• 10:50
  the clinic. So you know our study is, is you
• 10:53
  know with gene therapy you have to do 5 year studies for safety,
• 10:56
  but primary endpoint is at one year and then we follow out
• 11:00
  patients to two years. So, so we're we're hopeful that
• 11:02
  we'll see something really quite positive.
• 11:04
  Yeah, and quite quickly. In the ground as well, yes.
• 11:08
  A lot of thoughts gone into. The yes, clinical development
• 11:11
  exactly. I guess as well as compliment if
• 11:14
  you're obviously advisor at BGV as well.
• 11:17
  I'm sure it's not wholly related to to funding, but how, how much
• 11:22
  does your experience in that role sort of not influence?
• 11:25
  But yeah, sure, give some background when you're thinking
• 11:28
  about clinical development. Absolutely.
• 11:30
  Funding these days. Is, yeah, yeah.
• 11:32
  Inextricably linked. To no absolutely number one, I
• 11:35
  think you know, and, and part of the reason I came into biotech
• 11:38
  is really to be at the forefront of innovation.
• 11:40
  And, and I think working with colleagues at BGB and and other
• 11:44
  investors, I think you get exposed to really what's going
• 11:47
  on in terms of innovation. And like you say, I think there
• 11:50
  are learnings. So you know, not necessarily
• 11:52
  directly related to the to the work with BGV, but coming back
• 11:56
  to our clinical trial, you know, I think if if we look at what
• 11:59
  others have done and you know your standard approach to a
• 12:02
  clinical trial is you do a baseline visit, you do
• 12:05
  assessments and then you intervene and see what happens
• 12:09
  to those measures. What we're doing in our trial is
• 12:13
  not just doing a single baseline visit.
• 12:15
  You know, we're mandating for our patients that they have a
• 12:18
  run in period of six months where we can monitor disease
• 12:22
  progression. And in that way, you know, we
• 12:25
  have a much better understanding of their disease dynamics before
• 12:29
  we intervene. And for example, we know in this
• 12:32
  disease, some patients progress very slowly and then those
• 12:37
  patients would you even treat if they're progressing really
• 12:40
  slowly? What's your, what's the
• 12:41
  probability you can demonstrate a treatment effect is very low?
• 12:45
  So, you know, part of what we're doing is making sure that
• 12:48
  patients really have disease progression so that actually
• 12:52
  you're you're you're focusing your ability to really impact
• 12:55
  that. Yeah.
• 12:56
  So, so I think being exposed to that environment really helps.
• 13:01
  And like I say, the, the work with BGV is super interesting.
• 13:04
  You know, I think being able to sort of give some advice and,
• 13:07
  and sort of also hear about some of the innovation that's
• 13:10
  happening in the space is great. And, and I think, you know, as
• 13:14
  we've discussed previously, you know, the eye is an area where
• 13:17
  there's a lot of innovation happening.
• 13:19
  You know, when we think about things like gene therapy, cell
• 13:21
  therapy, lots of clinical trials, lots of interest and
• 13:26
  then really to me that's going to be the forefront of, you
• 13:29
  know, we'll, we'll often demonstrate the potential of
• 13:31
  these new approaches in the eye and then there's that potential
• 13:34
  to take them broader. Yeah.
• 13:36
  I mean, it's a relative safe haven for.
• 13:39
  It is absolutely the. You're also running the.
• 13:42
  History study. Yeah, exactly.
• 13:44
  Yes, yeah. Which forms a part of it as.
• 13:46
  Well, yes, and. Obviously you're moving forward
• 13:49
  into a massive period of just. Execution.
• 13:51
  Absolutely. Absolutely.
• 13:53
  You've been involved in much bigger businesses than
• 13:57
  complement as well. What are you going to take from
• 13:59
  your time at the Lights and Novartis and and Bayer?
• 14:02
  Absolutely, Yeah, No, I mean, I think I think, you know, that
• 14:06
  that was a great foundation to really have expertise in the
• 14:09
  space. But I think, you know, coming
• 14:11
  back to some of the earlier discussion, I think with all of
• 14:15
  these things, it's often and most importantly about the
• 14:18
  people. You know, I think it's great to
• 14:20
  have innovation, like I said. But actually, I think, you know,
• 14:23
  one of the lessons from those companies was, you know,
• 14:26
  building teams, driving that sort of motivation,
• 14:29
  incentivizing them, motivating them to really deliver.
• 14:33
  And I think that's something that we've replicated a
• 14:35
  compliment and and that really rings true in terms of our
• 14:38
  achievements. So, you know, I think, and then
• 14:41
  I think on top of that, having that network, you know, I think
• 14:44
  of, you know, being able to, to call on friends and colleagues
• 14:49
  who I've worked with before, you know, get their take on things,
• 14:52
  you know, how is that how, how would this be perceived by a
• 14:55
  pharma company? So, so I think, you know, all of
• 14:58
  those coming together very nicely.
• 15:00
  And then beyond that and, and something again, very important
• 15:03
  is having that network amongst the clinic clinical community.
• 15:07
  Yeah, of course, you know, having the right advisors, you
• 15:10
  know, working with the right investigators, making sure that,
• 15:12
  you know, they can support us as we go on this journey.
• 15:15
  So I think, you know, to me it's been a great sort of experience.
• 15:20
  And you know, I think something that we often maybe don't
• 15:24
  appreciate as much we, we take it for granted that our vision
• 15:27
  is great. I think when we talk to
• 15:30
  clinicians, when you talk to patients often you, you really
• 15:34
  appreciate how much they value vision.
• 15:37
  It's the one sense that actually if we think about often, if we
• 15:42
  if we were to lose that ability, it's the one that patients
• 15:46
  really fear the most and we fear the most.
• 15:48
  Yeah. So I think being able to have
• 15:51
  such a meaningful impact is really important.
• 15:54
  And I've been very fortunate. I've worked on products that
• 15:56
  really have had that profound impact, almost transformational.
• 16:00
  Yeah, in terms of patient outcomes, yeah.
• 16:03
  Nice, for sure. Cool.
• 16:04
  So enrollment started, Yes, initial data about a year from
• 16:09
  now. I think so our plan is by the
• 16:11
  end of this year to have around about 40 patients treated and
• 16:15
  we'll have variable levels of follow up for those patients.
• 16:19
  We have the option to to do an interim analysis in our study
• 16:22
  towards the end of next year. So once all patients and we're
• 16:25
  planning to enroll 75 patients. So quite a big trial for the
• 16:29
  first in human, but we've powered it on one of those
• 16:32
  endpoints that I mentioned and and I think that will give us
• 16:35
  that first indication of are we seeing something meaningful.
• 16:39
  So that's at six months follow up for all patients and then
• 16:43
  beyond that we anticipate the full one year read out around
• 16:46
  the middle of 2028. Got you.
• 16:49
  Understood. Cool.
• 16:50
  And then I guess tied into that data on the funding side, got to
• 16:54
  ask. Yes.
• 16:56
  Been a better start to the. Year.
• 16:57
  Absolutely. When?
• 16:58
  We last caught up at 2 frees, but yeah, how are things going
• 17:02
  on on that front? Do you expect any news in the
• 17:05
  next? Period.
• 17:06
  No, we're, we're very fortunate. We we raised the Series A round.
• 17:09
  We have a fantastic syndicate of investors.
• 17:12
  Yeah, they've been super supportive, you know, really
• 17:14
  believed in US and the team. Yeah.
• 17:16
  And, and really helped us execute.
• 17:18
  And I think certainly, like you say, the beginning of this year,
• 17:22
  there looks like some very promising, yeah, the, the
• 17:26
  environment is looking very promising, you know, in terms of
• 17:29
  green shoots, some IPOs, which, you know, seem to be going
• 17:32
  fairly well. And, and, you know, generally
• 17:34
  the sentiment is that raising money is better based on on the
• 17:39
  support we've had from our investors.
• 17:41
  You know, we have cash one way through to the end of our study.
• 17:44
  So, so that's a great place to be because in a way that allows
• 17:48
  us to focus on execution and not worry too much about the
• 17:52
  financing piece. But you know what, what are the,
• 17:54
  what are the sayings in, in biotech is, you know, as ACEO
• 17:58
  you're, you're never not, not, you know, raising money, you're
• 18:00
  always in that environment. And, and, and I think that you
• 18:04
  say the fact that the environment is quite positive.
• 18:08
  We'll continue to sort of check the temperature always thinking
• 18:12
  about, OK, what's that next phase look like?
• 18:15
  So, so we're already thinking about that and planning for that
• 18:18
  and then you know, we'll be reaching out to, you know the
• 18:21
  right sort of partners in the ecosystem over the next 1218
• 18:25
  months. And I think particularly as we
• 18:27
  start to generate data, you know, I think that gives us a
• 18:30
  lot more currency in terms of getting interest.
• 18:33
  But certainly we are already thinking about what does that
• 18:36
  next phase look like. It's.
• 18:37
  A nice position to. Be absolutely not under
• 18:39
  pressure. Absolutely.
• 18:40
  With options. And then just a final point I
• 18:43
  wanted to touch on like the other potential, yes, uses for
• 18:47
  for the platform for technology, Yeah, outside of ophthalmology
• 18:51
  or the outside of AFV as well. Yes and yeah.
• 18:55
  Give us your take on on that. Yeah.
• 18:57
  So, so I think what we what we've done is because we've
• 19:00
  built such great expertise in the eye, you know, with the
• 19:04
  right sort of talent and and real superstars there.
• 19:07
  Yeah, I think our focus initially like you say is the
• 19:10
  lead asset. But actually when we think about
• 19:12
  complement dysregulation #1 we see other ocular indications
• 19:18
  where we could potentially repurpose and redesign our
• 19:21
  approach. So I think we'll focus a little
• 19:24
  bit there. I think secondarily, what we
• 19:27
  know is GAAMD is multi factorial.
• 19:31
  So complement is an important driver.
• 19:33
  It's the validated driver of disease.
• 19:36
  But could we add another mechanism on top of that?
• 19:39
  And, and there's a concept of bisystronic vectors where you
• 19:43
  have two trans genes in the single vector and our trans gene
• 19:46
  is small enough that we can actually package another trans
• 19:50
  gene into the AAV and therefore address multiple pathways.
• 19:54
  So our research team are working on some of those ideas as well.
• 19:58
  And then beyond that, as we've mentioned earlier, complement
• 20:01
  dysregulation is implicated in the host of other inflammatory
• 20:04
  diseases. And often we're discussing what
• 20:07
  about other systemic indication. And like you said, that may not
• 20:10
  be gene therapy, that might be a different biological approach.
• 20:15
  So you know, I think there's a lot to play for, but one of the
• 20:18
  challenges with biotech is focus because often you're limited in
• 20:22
  terms of resources. So actually.
• 20:25
  Part of what we're doing with, with the support of our
• 20:27
  investors and our board is really laying out different
• 20:31
  options and saying, OK, where do we prioritize and, and where do
• 20:34
  we believe we can have the most impact and really, you know,
• 20:37
  making decisions on that basis. Yeah, don't run before you can.
• 20:41
  Walk, absolutely, absolutely. But you know, I'd like you to
• 20:43
  say taking taking the lead asset into the clinic really builds a
• 20:47
  strong foundation and then I think we can build on that.
• 20:50
  Nice. Well, certainly an exciting year
• 20:52
  ahead. It is.
• 20:53
  Thanks for coming on and sharing.
• 20:55
  It brilliant. No thanks, Callum, very much
• 20:56
  appreciate it. Yes, very good.
• 20:58
  Yes, brilliant. Thank you.