Latest / The BioHub - by Avetix / Episode 218 - JD Finley & Mitch Jones - Palisade Bio

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Episode 218 - JD Finley & Mitch Jones - Palisade Bio · The BioHub - by Avetix

• 0:06
  JD Mitch, welcome to the Biohub podcast.
• 0:09
  Great to have you on. Thanks for having us.
• 0:12
  Thanks, Carl. Awesome.
• 0:13
  Looking forward to featuring the Palisades story.
• 0:15
  It's been, yeah, an exciting year for you guys so far.
• 0:20
  Just before we get into, I guess the company and the recent
• 0:25
  milestones and a little bit more on the technical side.
• 0:28
  I always think it's useful for the listeners to hear a little
• 0:32
  bit more about who they're listening to, right and and your
• 0:35
  own individual journeys through through biotech, JDI.
• 0:38
  Don't know if you want to kick us off, but I thought it'd be
• 0:41
  useful to to get an insight into your background.
• 0:44
  Yeah, no, I'd be happy to. It's, it's interesting, Callum
• 0:46
  I, I started my undergrad in pre Med and then kind of along the
• 0:51
  way shifted to finance and accounting.
• 0:54
  Yeah. And so I kind of found my way
• 0:57
  back to the life sciences in in one way or another.
• 1:00
  I was introduced to this company about 12 years ago.
• 1:05
  I was, I was an investment banker at the time help raise
• 1:09
  about $15 million to to further the program they were developing
• 1:15
  at the time. And then we kind of ran that
• 1:19
  through a phase two. And about 3 years ago, it was
• 1:21
  just about 3 years ago, we had a readout of of our lead program
• 1:26
  there and learned that we had to abandon that program.
• 1:30
  And what was interesting is that we were in the process of hiring
• 1:34
  Mitch as our Chief Medical Officer at the time and Mitch
• 1:39
  said, hey, I have an asset that I think you guys would love to
• 1:43
  develop and I'll, you know if we can acquire that asset, I'll
• 1:46
  join you guys and we can Co develop that.
• 1:48
  And that's really what got us on this PD4 inhibitor was a little
• 1:54
  bit of serendipity and and the fact that Mitch had been
• 1:58
  following this this asset for a while.
• 2:00
  And so that's kind of how we got to where we are.
• 2:03
  I was, you know, I was, I was originally asked after I raised
• 2:06
  that $15 million Callum, I was asked to, to join the Board of
• 2:10
  directors and along the way they asked me to become the, the full
• 2:13
  time CFO, which I did. And then four years ago I took
• 2:17
  over as CEO of the company. And then, like I said, three
• 2:20
  years ago, we we found Mitch and and started this brand new
• 2:24
  journey with with Palli 21 O 8. Nice, awesome, Mitch, anything
• 2:30
  to add? Yeah, no thank you.
• 2:32
  I mean, my background, I'm an MD, so clinical medicine, also a
• 2:38
  PhD, biomedical engineering, been a founder at a couple of
• 2:43
  companies in a similar space, been sort of various clinical
• 2:50
  roles, senior level clinical or translational roles in publicly
• 2:55
  traded companies in the US, including some in IBD, a number
• 2:59
  in IBD and then join Palisade about 3 years ago, as JD points
• 3:07
  out, we sort of pivoted the company around the in licence
• 3:11
  and basically acquisition of the assets of a company called Giant
• 3:14
  Pharma. So, and we've been sort of
• 3:17
  working at that ever since CMO initially announced CMO
• 3:21
  President. Nice, it's an awesome story for
• 3:24
  sure. JD didn't quite realise how long
• 3:27
  your story with Palisade was going 12 years back.
• 3:31
  And what made you feel so strongly about the asset in
• 3:35
  particular? Mitch, because you know, you're
• 3:37
  well versed in the IBD space, you've seen a lot what really
• 3:40
  stood out. Yeah.
• 3:42
  So I'd spent a fair bit of time on the translational side
• 3:46
  looking at various mechanisms, whether it's the TNF inhibitors
• 3:52
  or the, you know, Illinois 20 threes or integrins or and
• 3:56
  looking at sort of could you dose topically locally.
• 4:00
  You know, my big thing is I'd spent, you know, a fair bit of
• 4:04
  my career on orally delivered, locally acting bio active, bio
• 4:09
  activated sort of immunomodulating drugs.
• 4:12
  And so through the research that I directed in IBD, eventually
• 4:20
  sort of came on to the idea that, you know, if you had
• 4:23
  something orally that was simple and chemical and elegant that
• 4:28
  could be bio activated locally and then acted the site of
• 4:32
  disease again in the PD4 space. Much like Verona Pharma that
• 4:37
  developed a BID oral, inhaled and then was acquired by Mark
• 4:41
  and COPD or with Arcutus, you know, oral or a topical pen
• 4:47
  inhibitor that's successful here we've got a way of delivering
• 4:51
  locally topically in the ilium and colon and IBD.
• 4:54
  And so that attracted me because you know what I was working on
• 4:58
  that time was fairly complex, whereas this is simple, you
• 5:01
  know, there's a historical reference.
• 5:03
  The drug sulfasalazine also uses microbiome produced enzyme to
• 5:08
  bio activate locally here. This drug was developed by
• 5:12
  medicinal chemists that knew that chemistry very well and so
• 5:16
  relied on those efforts to to make what was is a very elegant
• 5:22
  and robust drug candidate. Yeah, Callum, I let me just add
• 5:27
  that it's important to note that the medicinal chemists, they
• 5:30
  were out of the Merc Frost Labs in Montreal, these guys
• 5:34
  specifically designed this PD4 inhibitor, the engineer from the
• 5:39
  ground up for IBD. And that's and then get we'll
• 5:42
  get into some of the the mechanistic benefits of that.
• 5:45
  But unlike most PD fours, which have, you know, shown good
• 5:50
  science for treating IBD, this one was not repurposed from
• 5:55
  another disease indication. This was engineered from the
• 5:59
  ground up for IBD. Yeah.
• 6:02
  No, that's interesting. It's a topic across the industry
• 6:04
  at the minute, I guess, right. These assets that come out of
• 6:07
  various platforms and you're sort of finding an indication
• 6:11
  for them, right, as opposed to something that's been designed
• 6:14
  with an end goal in mind right from the start.
• 6:17
  It's interesting. PD 4 like as a target obviously
• 6:23
  that's had some issues before, right, in terms of like
• 6:26
  tolerability and whatnot. Of course, systemically, in
• 6:30
  particular, do you want to walk us through a little bit about
• 6:34
  the, I guess the mechanism that you guys are are working on
• 6:38
  which maybe perhaps solves a few of those issues?
• 6:41
  Yeah, no. And and so for PD4 inhibitors,
• 6:45
  often times the tolerability issues for the earlier
• 6:49
  generation PAN inhibitors have been that direct exposure to
• 6:53
  upper gut tissues in some patients can cause a secretory
• 6:57
  diarrhea. And then with changes, because
• 7:01
  these are immediate release drugs and systemically delivered
• 7:05
  drugs, those changes in concentration can affect the
• 7:09
  brain stem, which can lead to nausea and headache.
• 7:14
  And So what we've done is instead of making you know, the
• 7:17
  drug more more specific from an isoform perspective to try and
• 7:23
  avoid some of the either diarrheal or CNS adverse
• 7:26
  effects, which are limiting the drug.
• 7:29
  Because an IBD with a greater inflammatory burden, you need
• 7:32
  much higher levels of drug as opposed to in psoriasis.
• 7:36
  If for instance, So what we've done is you know it's an oral
• 7:41
  pro drug locally bio activated avoids direct contact with
• 7:45
  upper, with upper GI where you've got CFTR channels that
• 7:49
  cause secretory diarrhea and then you've got a very slow
• 7:53
  release profile where the the peak to through ratio is is
• 7:58
  limited. And so that improves the
• 7:59
  therapeutic index of the drug. And we found in our two most
• 8:04
  recent studies with 30, you know, up to 30 milligrams once
• 8:07
  daily, we found that very, very few PDE 4 related adverse
• 8:11
  effects actually in those two study, none.
• 8:14
  I think in one study of FSCD patients, we had two total
• 8:17
  adverse events in 10 patient weeks.
• 8:20
  And in the normal healthy study we had, you know, one AE that
• 8:23
  wasn't even treatment related. So very low profile.
• 8:27
  Awesome. Yeah, that's super interesting.
• 8:31
  I guess that differentiates you from maybe some of the other
• 8:34
  names looking at that, that potential mode of action in the
• 8:38
  IBD space for sure. Yeah.
• 8:39
  And. What's important, Callum, is
• 8:41
  that we're achieving high levels of plasma concentration, you
• 8:45
  know, above IC 90, but we're doing it as Mitch was saying, by
• 8:50
  by having the drug enter the the disease tissue 1st and then
• 8:53
  being released from there into plasma.
• 8:56
  And So what that allows is we have much, much higher
• 8:59
  concentration of drug in tissue directly like 7 times IC 90 and
• 9:06
  then but we're still able to achieve IC90 and plasma.
• 9:08
  And that's important because you need systemic distribution of
• 9:11
  the drug. But as Mitch was saying, what
• 9:14
  you don't need are those are those wild swings in, in peak to
• 9:18
  through and here because it's release more systematically and
• 9:23
  and slowly and you're, you're getting nice good level
• 9:28
  absorption in the in the plasma above IC90 without all the peaks
• 9:33
  that create the adverse events. Yeah, absolutely.
• 9:37
  Do you do you want to get into a little bit on, on the phase one
• 9:40
  then? Because obviously we touched on
• 9:41
  the sort of safety profiling of it, but I know there's some
• 9:44
  interesting data from that study from from a different angle as
• 9:48
  well. Yeah.
• 9:50
  Do you want to explain sort of what you saw in in that phase
• 9:53
  one and and sort of where it takes you looking ahead to to
• 9:56
  Phase 2? Sure.
• 9:57
  Yeah, I'll try and sort of keep it as concise as I can.
• 10:01
  I mean, the company did you know a gold standard phase one single
• 10:06
  ascending dose, multiple ascending dose study followed by
• 10:10
  a food effects crossover study. We took a Max tolerated dose
• 10:14
  into AUC cohort of five patients.
• 10:19
  So in the, in the Sabbat food effects, it was like, you know,
• 10:21
  something like 84 patients. And then in in the phase 1B
• 10:26
  cohort of UC patients, we treated 5 UC patients with a Max
• 10:31
  tolerated dose and we did that over just a week.
• 10:36
  So in just one week we saw you know, a 30% increase in cyclic
• 10:41
  AMP in in gut tissue, in colon tissue we saw a 40% reduction in
• 10:46
  the total lymphocyte count in the tissues.
• 10:49
  We saw a 70% improvement in PD4 B, 70% down on on fecal Calpro,
• 10:55
  a primary inflammatory biomarker and 15% on CRP sort of more
• 11:00
  systemic inflammatory marker. We saw 30 to 60% improvement in
• 11:05
  histologic scores and and we saw 100% response and 40% remission
• 11:11
  on modified Mayo score. So a really impressive change
• 11:16
  both both in biomarker cystology and clinical score in just a
• 11:19
  week. And then we took a once daily
• 11:22
  dose of 30 milligrams into an FSCD study actually started at
• 11:26
  20, then 25 and 30 and treated another five patients over 2
• 11:30
  weeks. We had just two adverse effects,
• 11:33
  1 fatigue and one discomfort over the entire study.
• 11:36
  We treated all patients for two weeks.
• 11:38
  And again, we saw something similar where we didn't know how
• 11:41
  the, you know, how the drug would act in fibrous stenotic
• 11:44
  Crohn's patients that are kind of refractory.
• 11:48
  We didn't know how much drug would be getting to tissue.
• 11:50
  We didn't know the PD effect, et cetera.
• 11:53
  So we measured in the ilium ascending and descending colon,
• 11:57
  we saw that we, we're getting enough drugs 7 times that tissue
• 12:00
  over plasma. We we saw a PD effect similar in
• 12:03
  size to what we saw in the colon at the Max tolerated dose.
• 12:07
  We saw a reduction in fecal Calpro, those were correlated
• 12:10
  tightly and an SESCD score improvement, the endoscopy score
• 12:14
  improvement of a 3.8 point drop on A on a baseline of 840%
• 12:21
  response, 40% improvement. So really good safety and
• 12:25
  efficacy in in the FSCD study. And by the way, these these
• 12:29
  results are consistent with what you see with other PD4
• 12:34
  inhibitors as well. So that the scientific part of
• 12:36
  this is pretty well understood and we're we're seeing the same
• 12:40
  kind of response. And it's the big issue is, is
• 12:43
  the reduction in adverse events, you know, making it a lot more
• 12:47
  tolerable. You know, one of the things that
• 12:49
  that I think we're very excited about is how quickly patients
• 12:54
  feel relief of their symptoms, their IBD symptoms once they
• 12:58
  take the drug. And that's a big deal, right,
• 13:00
  too. They, they want to feel better
• 13:03
  now, not, you know, not 12 weeks from now.
• 13:07
  And and by the same token, they don't want to trade, you know,
• 13:10
  they don't want to trade discomfort from their disease
• 13:13
  with discomfort from the drug, right.
• 13:15
  And so I think that's where we're kind of excited about what
• 13:17
  we're able to deliver to patients and.
• 13:20
  Maybe just to to follow on there with, you know to JD's point, I
• 13:24
  mean we are seeing and do predict that very high degrees
• 13:29
  of efficacy sort of beyond what was seen with a premolast.
• 13:33
  You know a premolast was sort of limited by tolerability.
• 13:36
  As JD points out, the Mufemilas study, the HEMA Pharma Mufemilas
• 13:41
  study showed indication leading efficacy, so 44% placebo
• 13:47
  adjusted remission with a dose response.
• 13:51
  Now they did start to see some pretty serious, you know, they
• 13:54
  saw a couple serious adverse events, they saw some AES, but
• 13:58
  still we think that we can get to that kind of similar kind of
• 14:02
  efficacy, but again with a much more tolerable drug.
• 14:06
  Yeah, got you. I mean, super exciting results
• 14:10
  for sure. And and I mean, JD to go back to
• 14:12
  your point as someone with family with Crohn's totally
• 14:15
  amplifies and relate to that, right.
• 14:18
  You don't want to notice the benefit 12 weeks down the line.
• 14:21
  You, you want it now because you're you're suffering
• 14:23
  basically. And I mean, generally it's a
• 14:26
  super impressive window in which you've or time frame, I should
• 14:30
  say in, in which you've, you've got through the phase one,
• 14:32
  right. Obviously you only really
• 14:34
  prioritised the drug three years ago.
• 14:37
  And now obviously the latest milestone is your, your phase
• 14:40
  two I and D clearance. And do you want to talk a little
• 14:44
  bit more about the the plan for that and and sort of what to
• 14:46
  expect? Yeah.
• 14:48
  Mitch, do you want to go through that timeline?
• 14:50
  Yeah, sure. So I mean, I think you know we
• 14:54
  when we unlicensed this, it was a preclinical asset.
• 14:57
  So we repeated all the proof of concept efficacy.
• 15:00
  We did all the GMP manufacturing, all the Ind
• 15:03
  readiness work. There's a lot of work that goes
• 15:04
  into getting a drug Ind ready. So obviously did the Phase 1.
• 15:10
  And so we're ready for our phase two study.
• 15:13
  We are starting two phase two studies, one in ulcerative
• 15:17
  colitis and one in Crohn's disease, both moderate to
• 15:20
  severely active patients. We have an ID approval from FDA
• 15:25
  on the UC study. We'll be submitting shortly on
• 15:29
  the Crohn's and expect an approval in Q3.
• 15:33
  We expect to start initiate both studies in in Q3 or the
• 15:39
  second-half really I think is what we're guiding to this year.
• 15:43
  And then expecting you know a readout, a top line readout in
• 15:47
  the UC study at the end of next year and then in the Chrome
• 15:51
  study which will be open label what we expect an interim read
• 15:55
  mid mid year next year. Exciting for sure JD, anything
• 16:00
  to add there or? No, no, I think you know, the,
• 16:03
  the, the team has worked obviously very hard in getting
• 16:06
  to where we're at. And one of the things when we
• 16:08
  did you, you, I mean everybody saw the, the financing we did
• 16:12
  last October, which you know, anyways was a brand new IPO of
• 16:16
  the company, sort of a re IPO of the company.
• 16:18
  But that that gave us that finally gave us the capital to
• 16:22
  go out and add very critical team members who are, you know,
• 16:26
  some world class drug developers and they've been all working in
• 16:30
  concert to get us to where we are now.
• 16:32
  And we're about to start treating patients in a phase two
• 16:35
  study on UC and couldn't be more excited.
• 16:39
  Yeah, for sure. You actually took the the next
• 16:41
  question right out of my mouth that I was, I was going to ask
• 16:43
  about the finances actually. So, yeah, I guess well
• 16:47
  capitalized to to make it through those next, next
• 16:50
  milestones. Yeah, we have, you know, we have
• 16:53
  enough cat. Well, we just, I think we just
• 16:55
  released our our queue and we have a little bit more than 120
• 16:58
  million still on the balance sheet as of June 30.
• 17:01
  And that's enough capital to get us through both of these phase
• 17:06
  two studies and then still have, you know, about a year's worth
• 17:09
  of runway leftover after that. Nice.
• 17:12
  Exciting. I guess just to maybe go back a
• 17:15
  little bit as well and had a question more more linked away
• 17:19
  sort of see the asset fitting into sort of the current
• 17:23
  treatment options available or in development in IBD and also
• 17:28
  long term with a company who are obviously single asset.
• 17:32
  We hear a lot these days about platforming A molecule and and
• 17:35
  whatnot. Yeah.
• 17:38
  How are you looking at things indication expansion wise or are
• 17:42
  you just focusing on on the free studies basically?
• 17:46
  Well, clearly our, our primary focus is on the UC and the, and
• 17:51
  the CD studies for our, our lead.
• 17:54
  I mean, we're, we're, we're not going to take our eye off that
• 17:57
  ball because that, that alone is could be an incredible
• 18:01
  monotherapy or at least a backbone therapy for treating
• 18:04
  IBD. But that said, we're continuing
• 18:07
  to look at other, you know, other opportunities and
• 18:10
  particularly where we think they'd be very synergistic to
• 18:13
  what we're doing. And then we're also pursuing
• 18:16
  some non clinical work in exploring, you know what
• 18:19
  combination therapies might look like, which one might benefit
• 18:22
  from pairing up with our drugs. So doing a lot of stuff on, you
• 18:26
  know on the side. But again, our focus is we are
• 18:29
  going to execute successfully on our on our main product.
• 18:33
  Yeah, I think that's right. I mean, there's, you know, a
• 18:35
  couple other comments that often times we get questions about,
• 18:38
  you know, the competitive landscape and you know, you
• 18:41
  know, you see being a crowded space.
• 18:43
  But if you sort of break it down and look at the future of
• 18:47
  treatment in IBD, we see sort of see, you know, the Duet study,
• 18:51
  the Vega study, the Spires approached with an, you know, IV
• 18:55
  sub Q, you know, fixed dose combinations.
• 18:59
  We see sort of see, you know, that that's going to probably
• 19:01
  happen in the oral space as well.
• 19:04
  And when you look at the oral space, I mean, in Crohn's, I
• 19:06
  believe there's one, you know, approved therapy, moderate to
• 19:09
  severe and with RINVOQ, but you know, and there's been sort of
• 19:13
  few in UC. And it, you know, I think if, if
• 19:17
  the future is, you know, oral, which patients prefer and
• 19:21
  clinicians still prefer. And if combos is, is, you know,
• 19:26
  maybe a distant after monotherapy with PDE for
• 19:30
  something that we're going to entertain, it's sort of less
• 19:33
  likely that you would want a combo maybe with, with Jack
• 19:36
  inhibitors, which have black box warning or S1 PS with, you know,
• 19:39
  sort of more efficacious in the UC.
• 19:42
  And you know, the, the Opethasmods, the Acoto cameras,
• 19:46
  2 drugs that are, you know, Avifax and J&J and likely to hit
• 19:50
  the market, you know, in the, in the coming years, it's sort of
• 19:54
  more likely that you would have a backbone therapy, maybe a PDE4
• 19:57
  with a symptomatic relief anti inflammation.
• 20:00
  And then add on those, those kinds of agents or other agents
• 20:05
  that are more mucosal healing or reprogramming the immune system
• 20:10
  for long term durability beyond that.
• 20:14
  So those are the kinds of things we're working on, we're sort of
• 20:16
  working with. Some of the best in the world in
• 20:19
  terms of AI driven multi omics kind of models and we're we're
• 20:24
  learning a lot and I think sort of more to come on that in the
• 20:28
  coming in the coming months. Yeah, nice.
• 20:31
  It's a great summary. And I guess, yeah, what you're
• 20:33
  saying is it's synergistic to not just the stuff that's on the
• 20:36
  market, but the stuff that looks like coming soon, I guess.
• 20:41
  Awesome. Cool.
• 20:42
  Well, look guys, thanks for the thanks for the summary.
• 20:45
  Yeah, I mean super exciting second-half of the year ahead
• 20:49
  for you guys. And and obviously sounds like
• 20:50
  2027 is going to be, yeah, a landmark year for for Palisade.
• 20:56
  We normally finish up with a bit more of a light hearted question
• 21:00
  rather than anything super technical or scientific, but
• 21:03
  yeah, sort of a standard Biohub question.
• 21:06
  So I'll, I'll ask you 2, but you may have some similar answers.
• 21:11
  Yeah. And that is if you were to have
• 21:12
  dinner with, with two scientists or entrepreneurs, past or
• 21:16
  present, who would who would they be and, and why?
• 21:19
  Well. I'm happy to go first.
• 21:22
  The the the first would be the first scientist past would be my
• 21:28
  my high school science teacher who was that he was a a retired
• 21:34
  Lieutenant in the US Navy who had survived the baton death
• 21:38
  March in World War 2. So I'd love to have dinner with
• 21:43
  him, you know, and be able to ask him more about that than
• 21:46
  about science, believe it or not.
• 21:49
  And then, you know, the, the, the current scientist would be
• 21:53
  Mitch. I'd love to.
• 21:54
  I'd love having dinner with Mitch, because first.
• 21:57
  Of all he. Picks good restaurants, but we
• 22:00
  we have a great time just talking about the science around
• 22:02
  our our own company and and I love that.
• 22:06
  Mitch, you have to choose JD now.
• 22:07
  Sorry you only get one option, but.
• 22:11
  Yeah, no, if there's just one option.
• 22:13
  I mean, I know probably a lot of folks who want to talk to Musk,
• 22:17
  but I think, you know, he's got, you know, rare ability to take
• 22:20
  problems that are, you know, constrained by convention,
• 22:23
  whether it's in space, energy, manufacturing and sort of reduce
• 22:27
  them the first principles. So I think in, in a
• 22:31
  conversation, you know, from what you're going to get, you
• 22:35
  know, from a dinner conversation, I think he'd be
• 22:37
  great to help understanding sort of the, the challenge of
• 22:41
  building, you know, the scientific, clinical,
• 22:45
  regulatory, financial infrastructure needed to sort of
• 22:49
  take a medicine to patients. And I think it'd be a
• 22:52
  fascinating sort of conversation on what we could do potentially
• 22:56
  to, you know, he's, he's sort of well known for designing
• 23:02
  differently. And so how can you get, you
• 23:04
  know, the discovery and development process to be, to be
• 23:08
  more efficient? And so I think that's good.
• 23:11
  I I'd invite. Yeah, nice.
• 23:14
  It is quite a popular answer, you're right.
• 23:17
  Yeah, maybe not everyone agrees on them on everything, but
• 23:20
  certainly an interesting way of thinking for sure.
• 23:22
  So cool. All right, guys, we'll wrap it
• 23:25
  up there. But again, thanks for coming on.
• 23:27
  Super excited to see the progress over the next 12
• 23:30
  months. Well, thanks for having us,
• 23:32
  Callum. We really appreciate it.
• 23:34
  Yeah, pleasure.