Latest / The BioHub - by Avetix / Episode 104 - Amir Hefni - CEO of Resolution Therapeutics

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Episode 104 - Amir Hefni - CEO of Resolution Therapeutics · The BioHub - by Avetix

• 0:04
  On this episode of the Biohub podcast, we're joined by Amir
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  Hefney, CEO of Resolution Therapeutics.
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  And Amir and the team are developing a new kind of cell
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  therapy, particularly in inflammatory and fibre optic
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  diseases and main target is the liver.
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  As I understand. Amir joins us as a head of a
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  pretty exciting 2026 for the team.
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  They've just dosed first patient in a Phase 1 two trial, so we're
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  going to hear some more about that and why they plan to take
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  things moving forward. But yeah, I mean, it's great to
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  have you on. Welcome to the pod.
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  Thank you, Calm. Great.
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  Great to be on and great to connect again.
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  For sure. Awesome.
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  I mean, typically we start off with me, I guess by just giving
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  the folks an insight into your own background.
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  I guess you're, yeah, pretty well established in in
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  biopharma, right? You work for some of the heavy
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  hitters, BMS, Novartis, Ipson. How have you found stepping into
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  a sort of early stage biotech with with resolution?
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  Yeah, No, no, it's, it's been, it's been a wonderful journey
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  actually. I was just reflecting on this
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  with, you know, it was out for dinner last night with, with
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  some friends and old colleagues and just reflecting on, you
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  know, it's a, it's been a really great adventure.
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  I think, you know, biotech, like it says on the tin, you know,
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  comes with some incredible highs and, and some some lows as well.
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  But even during those lows, you know, you have when you're
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  working with such a talented team and everyone pulls
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  together, it's a small organization, it's nimble, it's
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  agile, solution oriented. And I think that creates just a
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  great environment to be able to overcome challenges and and be
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  solution driven and, and overcome those.
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  So, you know, it's been it's been fun, it's been a fantastic
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  coming up to 2 1/2 years now in in Rule and have loved every
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  moment. Yeah, maybe, maybe if you ask me
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  there, maybe every moment might be a stretch, at least 90% of
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  the moments. For sure, every moment will be a
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  stretch, but I think we're all in that boat with anything we're
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  doing tonight. So particularly biotech.
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  Nice. I mean, you're well used to it
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  now, right? Like you say, you're 2 1/2 years
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  in, but what was the adjustment line?
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  Did you have to change anything about how you're approaching
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  certain things, or did it just come fairly naturally?
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  Yeah, I think when you, when you move, I mean, you know, my move
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  was from Novartis, which is a, you know, fantastic company to,
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  to, to resolution Therapeutics. I mean clearly Novartis with the
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  the backing of, you know, being being based in Basel, you know,
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  the backing of of a huge organization that that's
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  available, that that's run across across the globe,
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  available in in many geographies around the world across therapy
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  areas and modalities. You access to resources is, is
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  really phenomenal. You take it for granted when
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  you're in that environment. And I think moving into, into
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  biotech, you know, you, you've got to rely on on everyone in
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  the team. You know, we're all, we're all
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  in this together. Everyone rolls their sleeves,
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  everyone gets involved. You know, we, we do, you know,
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  occasionally have to look at expertise externally and get
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  external advice. But largely speaking, you know,
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  that small team that makes everything happen from, you
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  know, our research and translational science team all
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  the way to taking into into human.
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  You know, as you mentioned, we dosed our first patient, we're
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  in the clinic where our development team working hard on
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  this. We've got our manufacturing
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  team, process development, analytics, supply chain, and of
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  course all the support functions that come with this are finance
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  team and, and HR and so on. So you know, the, the, the team
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  really comes together to, to make it all happen.
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  And it's a, it's a small organization where 55 people
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  across, you know, Edinburgh and London largely.
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  We've got a couple of folk now based on the East Coast of the
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  US, but you know, everything is, is, is done in house.
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  Yeah, you've got to pack a punch, right?
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  Small team, got to do all the same stuff basically.
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  But. Absolutely, absolutely.
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  And and you know, partners become really important as well.
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  So we, you know, have very built very close relationships with
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  our CRO, with our CDMO, which is really critical in the space, in
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  the space of of cell therapy given how close you are to the
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  patient and the physicians. And you want to make sure that
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  you know that, that, that everything arrives on time.
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  And we we definitely owe that to our patients.
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  Yeah, absolutely. I mean you mentioned that and
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  we're just then the technology is obviously from the
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  university, right. Do you want to give a little bit
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  of background as to what it is you guys are developing and and
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  sort of the high level science of it, I guess I mean?
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  Yeah, with pleasure. I mean, I'm, I'm very, you know,
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  I, I never went to university or grew up in, in Edinburgh, but I,
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  I feel like I'm a, I'm a, I'm an ambassador for Scotland and, and
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  for Edinburgh since, since taking on this role, I think the
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  University of Edinburgh is truly a wonderful place.
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  And, and I have the privilege and, and our team, you know, is
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  based very close in the proximity of the University of
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  Edinburgh. So as you say, Callum, we'll
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  respond out from the University of Edinburgh, largely driven by
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  the great work of Professor Stewart Forbes.
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  Professor Forbes is a professor of regenerative medicine at the
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  University of Edinburgh and a hepatologist.
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  So he did a lot of preclinical work, about 15 years worth of
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  preclinical work looking at macrophages and how they operate
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  in the liver and the impact they can have in cirrhosis.
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  And actually took this, translated this from a kind of
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  vivo Preclinical Research into a clinic.
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  So 2 MRC sponsored studies of phase one and phase two study in
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  totality about 35 patients treated and really demonstrated,
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  you know, the transformational in, you know, outcomes for
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  patients with cirrhosis by utilizing macrophage cell
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  therapy. So he demonstrated that those
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  macrophages are able to what we would call them regenerative
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  macrophages. They're able to reduce
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  inflammation in the liver, resolve fibrosis, allow the
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  liver to to regenerate and ultimately the patient to
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  recover. So that's really foundational to
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  why Resolution Therapeutics was created in the first place.
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  Absolutely. And as I understand the science
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  and bear in mind, I'm not the finest scientific mind of my
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  generation by any stretch. But obviously it gets to a point
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  in those kind of diseases where macrophages actually play a role
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  in the inflammatory process, right?
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  It can go too far. But you guys are intervening
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  early to prevent that happening, I guess.
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  And yeah, contribute to yeah potentially curative treatments
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  for for liver cirrhosis and end stage liver disease.
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  So I'll, I'll, I'll let me unpack your, your, your so.
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  So first of all, I think it's really important to highlight
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  that you're, you're absolutely right.
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  Macrophages come in in varying phenotypes traditionally or
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  called the M1 or M2 phenotype. Nowadays, the terminology has
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  evolved. In summary, you can get prone
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  inflammatory macrophages. Those are macrophages that
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  deliver inflammatory cytokines and and work to engulf, you
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  know, for example, when we know some some colleagues and friends
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  of ours and and other companies that are using that approach to
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  target oncological malignancies. For example, in our case, we're
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  100% focus on what we call the regenerative phenotype of the
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  macrophage. Those are macrophages that are
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  anti-inflammatory, they're antifibrotic and again, looking
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  at reduce inflammation, resolve fibrosis, allow organ
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  regeneration, the patient to recover.
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  So I think that's, that's, that's really important to
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  highlight, but also a very important point as well is that
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  we actually through the, the apheresis process in patients,
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  we don't take out the macrophages.
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  We actually take out the monocytes, which then
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  differentiate into the macrophage.
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  So we're able to, the reason why we take out the monocytes is
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  because we can then control the incubation parameters, the
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  cytokine mix that ensures that they get differentiated from a
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  monocyte into the right type of phenotype of the macrophage and
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  they get phenotype locked. And soon when they're introduced
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  into a highly inflamed environment, they do act in
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  anti-inflammatory antifibrotic way.
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  And ultimately we see those clinical benefits as Professor
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  Forbes demonstrated in the clinic.
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  Yeah. For sure.
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  Understood. That's that's really helpful.
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  What are the current treatment options for yeah patients in in
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  that case, that doesn't seem to be a ton out there, right?
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  Yeah. I mean, you know, Professor
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  Forbes did his study in a largely compensated cirrhotic
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  patient population, although many of the patients had a prior
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  decompensation for our clinical program, what we've been able to
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  do is engineer the macrophages. So the macrophages exhibit even
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  greater anti-inflammatory, anti fibrotic properties and we
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  believe that will enable us to be able to treat patients that
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  are even sicker than the ones we saw in Professor Forbes clinical
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  study. So I would call our, our patient
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  population a decompensated patient population.
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  You know, for these patients today, unfortunately the only
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  treatment option is a liver transplant.
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  And as, as you can imagine, you know, challenges with donor
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  availability, complexity of surgery and, and, and, and
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  aftercare. And and so we're looking to
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  really try to address a a major high unmet need in this therapy
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  area. Yeah.
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  For sure, I can imagine the wait list for liver transplant isn't
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  particularly short by any stretch of the imagination.
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  Very good. I mean I touched on it on the
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  introduction, but you guys have just started, just started
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  dosing on the Phase 1 two trial. Can you run us through a little
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  bit about that the the strategy behind it and in the UK and also
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  Spain I think as well. And yeah, when can we expect
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  some initial data from that, I guess, Yeah, yeah.
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  So thanks, Calm. So yes, we, we, you know, we're
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  probably one of the most incredible moments in, in my
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  professional life was, was being in Edinburgh when, when the
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  first patient was being dosed. So, you know, we're really
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  pleased that, you know, the patients done very well.
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  There were no major adverse events reported, patients back
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  home with their family, which is which is fantastic.
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  Yeah. And what does that mean?
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  So, you know, we, we had a a safety stop after dosing the
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  first patient to give the DSMC an opportunity to review the
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  data and ensure that it's safe for us to continue.
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  This is standard practice for a phase 1-2 clinical study.
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  DSMC gave us the, the green light and we were able to move
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  forward with, you know, the, the full study, which is fantastic.
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  So as you mentioned Calum, we're, we're now active across
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  14 sites across the UK and Spain.
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  We're looking to, to hopefully deliver our first interim
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  analysis in, in 2026, so probably the latter latter
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  period of 2026 and that's what we're aiming for right now.
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  Nice. Understood.
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  And that's in the indication you mentioned before I guess the
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  what you guys are doing, it sounds like on the face of it,
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  it has potentially other uses as as as well, right.
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  Is that something you're looking at with the the translational
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  team? Yeah, no, absolutely.
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  Our, our research and translational science team is,
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  is working really hard on evaluating our lead asset RTX
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  001, which is in clinic now for, for end stage liver disease or
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  decompensated liver disease. But we've also engineered a
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  second asset where we are looking of into, into
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  potentially 2 indications in the preclinical setting.
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  I just want to make sure that it's not in the clinic, it's in
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  a preclinical setting, but in areas like lung fibrosis and and
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  GBHD, again, subcategories of both of those diseases that have
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  a very high unmet need. And and you know, if we're able
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  to to help these patients will be a tremendous addition to you
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  know, therapeutic options for for this patient population.
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  And and hopefully again, we're aiming to have preclinical data
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  on both of these indications sometime in 2026 as well.
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  Not it. Well, exciting.
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  And it sounds like next year's Really.
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  Yeah, it's. A big gear full of mouth.
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  Of stones, yeah, how fresh it absolutely cool.
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  I know something we touched on with when we made the
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  introduction as well was, was building in in the UK, right.
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  I mean, I know you mentioned the the technology from Edinburgh
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  offices down in London. Like I think we touched on that
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  maybe the UK is getting a little bit of stick reputation if yeah,
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  biotech investment at the minute and we're seeing some big deals
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  pulled by the yeah, big pharma and whatnot.
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  But how have you found the sort of general ecosystem you've
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  obviously been building? Yeah, over the past 2 1/2 years,
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  the business, the platform science, but mainly the team,
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  right, Yeah. How's it, how's it been for you
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  and and and where do you think it could maybe be tweaked and
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  improved a little bit? I.
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  Think that's a very loaded question, Cal and, and let me
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  yeah, let me, let me share my, my, my opinion.
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  I think we, you know, the, the way that we structured our
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  resolution therapeutics is we have our research and
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  translational science team headquartered in in Edinburgh.
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  We have our process development team both in post development
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  analytics supply chain largely well supply chains between
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  London and Edinburgh, but our process development analytics
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  team largely based out of London.
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  So we, we have a A2 site strategy for resolution
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  therapeutics. What's that, what's that that
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  that's led to is, is the ability to recruit fantastic talent
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  like, or I think the UK has a fantastic academic institutions,
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  world leading. And I think that translates into
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  fantastic, you know, BSCMSCPHD students that are coming out
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  that that we can hire and and add a tremendous amount of value
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  to to our organization. So I think that's that's on
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  that's on the positive front. I think some of the challenges
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  become, you know, a little bit that gets a little bit more
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  tricky once you get into the clinic, right, because we know
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  that the NHS is a fantastic, you know, institution.
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  My father spent his entire career working in NHS, my mother
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  for part of her career working in NHS.
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  So my, my kids were born in the NHS.
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  So, you know, it's very dear to, to me on, on multiple levels.
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  And like, like many of us, but, but at the same time, it's under
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  a tremendous amount of pressure, right?
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  And it's, you know, speak to friends and, and, and, and you
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  know, that are in the NHS working extremely hard.
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  It's, it's not an easy environment.
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  So I think that's where there's an opportunity for us as a
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  country to enable, you know, faster site opening to enable
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  foster recruitment and, and ultimately to have the world
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  leading clinical programs come to the UK.
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  And you know, I, I, I know there's a lot of work going on
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  behind the scenes with the science strategy and so on to
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  try to enable this. And I really hope it it bears
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  fruit. I mean, you first hand the
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  experience of it, right, Because I mean, your trials are running
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  in the UK, so you're well positioned to to talk about
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  that. Lowe's.
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  Yeah, I know. We're, we're, we're, look,
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  we're, we're, we're solution oriented company, you know, we,
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  we want to make sure that we're trying to help the ecosystem as
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  well. So we've been given feedback in
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  real time to, you know, NHS leadership and, and we've gone
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  through multiple avenues to share some of the experiences
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  that we've had. We've been able to contrast that
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  with experiences that we've had in Spain.
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  For example, we have equal amount of sites active in the UK
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  and Spain. So I think that's really helpful
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  to provide that insights and and hopefully we can see, you know,
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  we can see progress in that area.
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  There's definitely a ton of potential, there's no doubt
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  about that. Yeah.
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  Absolutely no. It's interesting how how have
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  you found the comparison between the UK and Spain?
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  Just out of curious. Cal, you're like you're, you're
• 16:34
  putting me in the spot here like it's too early, right?
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  We we, we've, we're, we're just opened, you know, a number of
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  these sites very recently. You know, I think I would say so
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  far we're, we're seeing kind of 5050 recruitment between between
• 16:49
  both countries. So but but, but the next few
• 16:53
  months we'll we'll be telling. So I'll, I'll hope I'll reserve,
• 16:57
  you know, a judgement until, until we we're able to complete
• 17:01
  enrollment. Yeah.
• 17:02
  Completely. Fair enough.
• 17:03
  Very good. Awesome.
• 17:04
  Well, we'll we'll have to pick up at the back end the next
• 17:06
  year. And the addicts fixed To Do
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  List. Yeah, awesome.
• 17:13
  All good. Well, now been great.
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  Great catching up, Amir. And yeah, really appreciate the
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  insight. I mean, you guys are certainly
• 17:21
  ones to watch for for next year. I guess we'll finish with a
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  typical Biohub question, if you don't mind, which is something I
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  mentioned before when we were doing the briefing.
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  But yeah, it's If you could have dinner with any scientist or
• 17:38
  entrepreneur, past or present, who would it be and why?
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  Entrepreneur, Entrepreneur past or present, or.
• 17:51
  Scientist. Or scientist, yeah, You know,
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  and I, I, I, it's a, it's a, it's a really, really great
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  question. I think maybe, maybe, maybe Jim
• 18:09
  Allison. Who, who's, who's one of one of,
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  you know, one of the, the, the people that won the Nobel Prize
• 18:19
  for discovering, you know, you know, oncology and, and
• 18:21
  especially the development of Epulumab, which led to a
• 18:25
  breakthrough in the treatment of Melanoma.
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  I think having dinner with him would be it would be truly
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  fantastic to to just get a sense of his journey, you know,
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  taking, taking this from an idea hypothesis all the way to
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  bringing it to, to life. And I was involved in the kind
• 18:44
  of back end and I went out to DMS and, and launching and
• 18:47
  seeing impact it had on patients.
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  But to have proper dinner with him would be, would be
• 18:54
  fantastic. You know, another person that's
• 18:57
  very close to our field right now is obviously Carl June, who
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  was one of The Pioneers of cell therapy.
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  And, and you know, that to the treatment of, of Emily
• 19:07
  Whitehead, which is truly phenomenal.
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  And, and one of the reasons why we're here today as a company as
• 19:12
  well. So I'll say probably those,
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  those two individuals, we would be fantastic to to have dinner
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  with them. Well, you never know, I guess
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  we'll see. Awesome.
• 19:22
  Now it's been great having you on.
• 19:24
  I think that's always a tough question to answer.
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  I mean, but I think the other one we sometimes ask is even
• 19:30
  harder and that's the advice you'd give to your 21 year old
• 19:32
  self. But we'll save that for next
• 19:34
  time. So much advice, so much advice.
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  I could be on here for an hour. I don't know how this don't do
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  this. Look, it's been awesome catching
• 19:47
  up and yeah, really appreciate the time and we'll stay in
• 19:52
  touch. Yeah.
• 19:53
  Thank you, Callum. Thanks for having me.