Latest / The BioHub - by Avetix / Episode 246 - Neil Warma - CEO, ProMIS Neurosciences

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Episode 246 - Neil Warma - CEO, ProMIS Neurosciences · The BioHub - by Avetix

0:06
Welcome back to the Bio Hub podcast by Avetix.
0:10
Today I'm joined by Neil Warmer, President and CEO of Promise
0:14
Neurosciences. Now, Neil has spent more than 25
0:17
years building and leading biotech companies globally, with
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a career spanning large farmer, emerging biotech and company
0:24
creation Promise. He's leading a differentiated
0:27
approach neurodegeneration, developing therapies that are
0:30
designed to selectively target the toxic, misfolded forms of
0:34
proteins believed to drive diseases including Alzheimer's,
0:37
ALS and Parkinson's. Alongside Promise, Neil also
0:41
leads Mongoose Bio and MD Anderson spin out developing
0:45
next generation TCR T cell therapies for solid tumors.
0:49
Today, we'll talk about Neil's journey from studying
0:52
neuroscience to becoming a biotech CEO, the lessons he has
0:56
taken from building companies across multiple markets, what
0:59
differentiates Promises platform and what it takes to translate
1:02
ambitious science into successful biotech companies.
1:05
Neil, it's a pleasure to have you with me today.
1:07
Thanks very much, Ben. I really appreciate you taking
1:09
the time to to listen to the story.
1:11
Yeah, of course. So, yeah, let's begin.
1:13
I mean, you started out with a neuroscience degree.
1:16
You moved into business through an MBA.
1:17
At what point did you ultimately realise that you wanted to build
1:22
and lead companies as opposed to just understanding the science?
1:26
Yeah, I think it was. It wasn't a formal decision
1:30
along the way, Ben, by any means.
1:31
It was more a series of steps and a series of introductions
1:34
and a series of opportunities that led to this, to this career
1:37
path that I've that I've come down.
1:39
So it wasn't really a desire, wasn't a desire to become ACEO,
1:42
to become a, you know, serial CEO.
1:45
It was really the opportunities that presented themselves.
1:48
And I think from the, you know, from the founding of my, of my
1:51
academic career, I guess with the, the neuroscience research
1:55
that I did for a number of years and really enjoyed and then did
1:58
an international MBA which took me overseas.
2:02
I think that was the first opportunity where I thought
2:05
there's a real importance to being able to combine the
2:09
science and the business, to be able to explain the business.
2:12
And I, I think when I ended up at Novartis and I spent 10 years
2:15
at Novartis, I really began to understand the importance.
2:19
And I love the science, the deep science.
2:20
I've always been fascinated with, with, with exciting
2:22
science. But then I think as I honed my
2:25
skills at Novartis on being able to interact with the scientists
2:28
and it was interesting, I had a global responsibility from the
2:31
outset at the at the global headquarters of Novartis.
2:35
So I interacted with a number of or all the various departments
2:39
within the, you know, large multinational at the
2:41
headquarters. So that was with research,
2:44
development, marketing, regulatory tech OPS.
2:47
So I got a good understanding of the sense of the multiple
2:49
aspects of different functions within a multinational
2:53
pharmaceutical company. Being on the business side,
2:56
which I was at Novartis, my job was to kind of explain to the
3:00
various stakeholders what we were doing, whether they were
3:03
internal or external stakeholders.
3:05
So I think from that point, it was really honing those skills
3:08
and developing the understanding and the ability to communicate
3:10
very detailed science in more of a business fashion as I did that
3:15
opportunities presented themselves.
3:16
And I think that's what really took me down this path of, you
3:20
know, opportunities to become, you know, eventually become ACEO
3:24
and do that several times over. So it's really a process of
3:28
opportunities and options available that led to led me to
3:31
kind of where I am today. Yeah.
3:33
And as you mentioned, there's been a number of different
3:36
aspects to your career. I mean, you know, Novartis to
3:39
founding and selling your own company, public company
3:41
leadership, you know, running a China US multinational biotech.
3:46
You went out to Korea and, you know, you now come back and
3:48
you're you're with promise. You know, talk us through some
3:51
of, I guess, the key inflection points during that journey that
3:54
have shaped how you'd lead today.
3:58
Sure, it's a bit of an eclectic path I guess as you as you look
4:01
back, but one that I'm, you know, honoured to have kind of
4:05
journeyed down. I think some of the inflection
4:07
points certainly, you know ending up at Novartis and
4:09
getting that understanding and training at a large
4:12
multinational at the corporate headquarters and in Switzerland
4:15
of all places was pretty fantastic.
4:17
From there it was, as I mentioned, it's very much
4:20
talking and meeting people and having opportunities and options
4:23
presented. And after Novartis was formed, I
4:27
was part of the integration team that brought Novartis together,
4:31
talking with scientists and talking with different people.
4:33
The opportunity presented itself to start my own company.
4:36
And even though Novartis wonderful company in the heart
4:39
of Europe career was nicely defined, I think it was the,
4:43
just the, the thinking of different opportunities and the
4:46
idea to, to create my own business plan with a partner of
4:49
mind and, and, you know, quit the comfortable life of, of
4:53
large pharma and jump into, you know, my own company.
4:56
That was a pivotal moment and very, very important to me to
5:00
leave the mothership, so to speak, move to New York City and
5:03
start my own company. And it, it brought out a whole
5:06
different element of me of having to, you know, manage for
5:08
myself, raise my own money, hire my own people.
5:11
And it was absolutely thrilling experience.
5:14
But then after we sold that company, you know, a really
5:18
interesting opportunity. I talked with folks back at
5:21
Novartis, they had a portfolio company that was looking for a
5:24
new CEO and it was that opportunity that was really the,
5:28
you know, first real CEO opportunity that was again
5:31
instrumental in my life. Ran that for a few years.
5:34
It was an introduction and an option to then step up and run a
5:37
public NASDAQ listed company which took me to Houston for a
5:40
number of years. And that was absolutely
5:42
fascinating. So a different realm, still very
5:44
entrepreneurial, different science if you will, but from
5:48
private to public from there meeting people, interacting with
5:52
people, we sold Opexa. There was an opportunity to
5:55
become the US CEO of a China LED company and that was very much
5:59
based on kind of trust. And you know, the the the trust
6:04
I developed with the founder of IMAP back in the day.
6:07
And for me, it was just the wanting to do something a little
6:10
bit different intellectually, a little bit different than the
6:12
idea of, you know, leveraging a Chinese company.
6:16
And that my role at IMAB was to build out the US footprint to
6:20
take the company public or to help take the company public,
6:23
which we did. So a brand new opportunity, but
6:26
it's all about options that became available to me.
6:28
So running that was absolute huge learning experience for me,
6:32
taking a Shanghai based company and expanding and taking a
6:35
public in the US From there, it was introductions and
6:38
opportunities to to step into running a South Korean company.
6:42
And because the first foreigner to ever run a South Korean
6:44
company was a kind of an exciting opportunity.
6:46
So those were all very different, but all certainly
6:50
inflection points in my career. And I think I've always strive
6:53
to do something a little different, a little creative.
6:56
You know, we've started a few companies over the years, but
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it's, it's nice for me again, keeps me, keeps me vibrant to do
7:02
things a little different to take on a China company role or
7:05
a South Korean company role and now stepping into promise with
7:08
some fantastic science. It's, it's been a, you know, a
7:10
fascinating journey filled with lots of interesting inflections
7:13
along the way. Yeah, and let's, I mean, let's
7:16
jump into promise now. I mean, you know, the the
7:19
company is built around a very specific idea targeting toxic,
7:23
misfolded form of a protein rather than the more visible or
7:28
abundant forms. For for someone who is less
7:31
ingrained within the neuroscience realm as you and I
7:33
are, how would you explain why that distinction could be so
7:37
important in diseases such as Alzheimer's?
7:41
Well, I think it's a very good question, Ben.
7:42
I think it's very important in probably all diseases is this
7:46
idea of becoming more selective, more precise in the targeting of
7:50
a specific target. And I think we've seen that over
7:54
the over the years, over the decades of drugs that are
7:55
becoming less, you know, kind of that shotgun approach and much
8:01
more precise in their targeting. And even though we've gotten
8:03
better at that over the years and we have with certainly with
8:08
Alzheimer's drugs that have come to market, but one of the key,
8:12
key points of differentiation or the key important points with
8:14
Alzheimer's disease is that becoming even more precise.
8:18
We have learned over the past number of years is absolutely
8:21
critical in treating Alzheimer's disease.
8:24
And by that I mean, when you look at kind of the, the target
8:27
and again we've, we've, we've gone specific with our target
8:30
and Alzheimer's looking at a specific protein.
8:33
And the one we and others are targeting is this amyloid beta
8:36
protein. And that's been well
8:38
characterized as a, as a key target that's driving cognitive
8:42
decline in Alzheimer's. But within the amyloid beta
8:45
protein, you've got different subspecies or different species
8:49
of that same protein. You've got the monomer species,
8:52
the oligomer species, the plaque species.
8:54
So there's different forms of the protein, all characterized
9:00
by amyloid beta. So as we become, you know, and
9:02
there's a need to become more and more and more precise, you
9:05
can say, well, you're targeting amyloid beta.
9:06
That's pretty precise. And it is.
9:08
But again, within those different species, some are
9:10
actual helpful forms of the amyloid beta protein and some
9:14
are not not helpful and are are are not really relevant to
9:18
disease progression either. So for us being having a
9:22
platform that allows us to design an antibody and we're
9:25
specifically targeting the oligomer species of amyloid beta
9:29
protein. And that's been a shift over the
9:31
years as the industry's developed and as we've seen kind
9:34
of off target or even on target toxicity targeting some of these
9:37
species of of amyloid beta protein.
9:40
That's when it's become absolutely critical to really
9:43
become more and more and more selective and precise with your
9:46
targeting of the drug for Alzheimer's disease.
9:49
And that's where I think Promise leads the field really in our
9:52
selectivity and having an antibody that is highly
9:55
selective to only the toxic form of amyloid beta protein, the one
9:59
that's really driving cognitive decline in patients.
10:02
Yeah. I mean, like, like like you
10:04
mentioned, you know, a lot of the Alzheimer's field when it
10:07
comes to drug development has been shaped by plaque reduction
10:11
and amyloid clearance. Well, when it comes to PMN 31-O,
10:16
what does best in class really need to mean, you know, beyond
10:19
just sort of simply being another anti amyloid antibody?
10:23
That's a very good question and best in classes I think is what
10:26
a lot of us or a lot of companies strive for.
10:29
You know you want to have a differentiated asset that has
10:32
the potential to be that best in class obviously in in a good
10:35
way. And one of the challenges we've
10:37
seen with anti amyloid therapies, you know, there's two
10:40
drugs on the market, donanemab, lecanemab.
10:43
Again, the, the challenge that's faced the industry is being able
10:49
to find and design a drug that is selective to only the harmful
10:54
toxic species. And what we're seeing with the
10:56
drugs on the market is that they're, they don't have that
10:59
selectivity profile that we do. So they bind all forms of
11:02
amyloid beta protein. And you're exactly correct that
11:05
over the past decades, plaque has thought to be the driving
11:09
cause of cognitive decline in Alzheimer's.
11:11
We now know that's not true. There are drugs that completely
11:15
eliminate plaque and patients continue to decline.
11:18
And what we're also seeing is that drugs that bind plaque or
11:23
clear plaque are also now responsible for a very serious
11:27
side effect. And the side effect is known as
11:29
Aria and it really specifically refers to swelling and bleeding
11:34
on the brain. As you can imagine, if you
11:37
target remove the plaque that's intertwined in the in the
11:40
vascular structure in the brain, if you pull that away, you'll
11:42
get rupture of the of the blood vessels in the brain and that
11:45
can lead to haemorrhage and it can lead to swelling in the
11:47
brain. So now we know that plaque is
11:50
really not sufficient or not that relevant for cognitive
11:53
decline. And on top of it, you've got
11:55
this bleeding and swelling side effect for drugs that hit and
11:59
target plaque. So it's become even more
12:02
important to design drugs that kind of avoid binding plaque and
12:09
somehow get at these toxic oligomers, which sit further
12:11
upstream. But now we know as an industry
12:14
that these toxic oligomers are the subspecies of a beta protein
12:18
that are driving cognitive decline.
12:20
But again the challenge is how do you design an antibody that
12:24
avoids plaque amyloid beta protein and hits oligomer a beta
12:30
protein and that's been a challenge to the industry and
12:32
that is where promises excelled. As I mentioned, we have our
12:36
antibody, we believe that avoids plaque and really targets the
12:40
toxic oligomer species and that sets us apart as having that
12:44
potential best in class treatment for Alzheimer's
12:47
disease. Yeah.
12:49
And you've, you've recently released 6 month blinded precise
12:53
AD data and that has, you know, it was encouraging safety data,
12:57
directional biomarker findings and we're still looking at
13:00
pooled blinded results. What do you essentially feel
13:05
that this data tells us about PMN 31-O?
13:09
And what are you not concluding until the study is unblinded?
13:14
That's a, a really interesting, really interesting way to phrase
13:16
the question because both those two elements are absolutely
13:19
important. What does it tell us?
13:21
And we're careful to interpret what it does tell us, but also
13:25
very importantly, what doesn't it tell us?
13:26
What comes up in six months with the final unblinded data.
13:29
But importantly, we we have this and we had this interim analysis
13:34
that we had built into our Phase 1B study and even stepping back
13:38
a little bit, the Phase 1B study that we're now running in at
13:43
promise. The decision on the design of
13:46
that study was probably the most important decision we made in
13:50
the company over the past several years.
13:52
We wanted to design a study and this is a 1B study, so first
13:56
first trial in patients. We wanted to design A1B study
14:00
that was going to give us a fairly definitive answer, which
14:03
meant we needed enough patients to show a signal, but we also
14:07
needed to carry this out at least 12 months so we could see
14:10
a clinical signal because not only biomarker movement and
14:13
safety, that's important, but we wanted that third bucket of
14:17
endpoint evaluation being related to clinical outcome.
14:20
So we've got a kind of atypically, I won't say
14:24
unprecedented, but we've got a very comprehensive robust Phase
14:27
1B study that we're currently running.
14:30
It's fully enrolled. We oversubscribed for the number
14:33
of patients. There's a lot of enthusiasm for
14:35
the study. And as you just mentioned, we
14:37
had built in an interim analysis.
14:39
So as I mentioned the patients are all treated for 12 months,
14:41
they're dosed for 12 months with PMN 310 and at the six month
14:45
time point. So when all had been treated for
14:47
six months instead of 12, we had a a revealing if you will of
14:52
blinded interim data and that we put out July 28th, so a month or
14:57
so ago where we looked at biomarker data and safety data.
15:02
We did not look at clinical outcome measures at all.
15:05
So biomarker and safety on a blinded on a blinded basis.
15:10
So we were setting expectations going into this interim analysis
15:13
as to what, you know, what people should expect to see and
15:17
we're very careful to maintain those expectations.
15:20
And we were expecting to see, you know, to be able to reveal
15:23
kind of a safety profile. Again, keep in mind, as I said
15:26
earlier, we have a, we believe we have an antibody that avoids
15:30
plaque and only targets the toxic oligomers.
15:33
And by avoiding plaque, we were expecting to see a far a much
15:37
improved safety profile. This Aria swelling and bleeding
15:40
on the brain. We felt we would be able to
15:42
significantly reduce the incidence of Aria.
15:46
So that would be an important finding, the interim analysis.
15:48
And then we'd also look at potential for target engagement.
15:51
And what we actually showed, which we presented on July 28th
15:55
was exactly that. We were, you know, we set
15:57
expectations for ourselves. I think we met those.
15:59
We probably kind of overachieved, if you will, on a
16:02
couple of them. The safety profile of PMN 310 on
16:06
a blinded interim look was superb.
16:08
We had 0 cases of our, the more serious form of Aria.
16:12
So the edema Aria, the, the swelling of the brain, 0 cases
16:15
of that, the background Aria H was, was similar to placebo.
16:22
So from a side effect, the swelling, bleeding component of
16:25
safety, we excelled there. We were really pleased with
16:28
that. The overall safety profile was
16:29
terrific. And then on the other side, just
16:31
to make sure that yes, we're safe, but is it doing anything?
16:34
We presented data, blinded data on two key biomarkers to, to see
16:40
if we had any sense of target engagement.
16:42
Was there a, an early drug effect that we were seeing?
16:45
And indeed we were, we showed with two important biomarkers, P
16:50
Tau 217, MTBR 243, we showed a decline in those biomarkers in
16:56
the first six months that was close to the randomization
17:00
schedule of the of the trial. So we were again very pleased
17:04
with both the safety and the the potential for target engagement
17:10
that we saw at the interim analysis.
17:11
And I think people overall, we had a, you know, we spoke to the
17:14
KOL community of the importance of, of, of coming with a, with
17:18
a, with an interesting interim result.
17:20
But to your second-half of that question, you know, it's very
17:23
important that we don't get too ahead of ourselves.
17:26
You know, again, we, I think in the, in the interim, we thought
17:28
we saw that we're heading in the right direction.
17:31
Things are looking quite interesting, but let's complete
17:34
the trial, get everybody fully dosed and then we'll unblind the
17:38
data and present fully unblinded data with the clinical results
17:43
in, about, in about 6 months from now.
17:45
So I think it gave us a very good signal that I think we've
17:48
de risked it or improved the, the likelihood of success
17:52
through an interim read. But again, we have to keep our,
17:55
you know, keep our, our, our, our, our heads, you know, firmly
17:59
focused on executing the rest of the trial and the true signal
18:02
comes, you know it. We've we've said publicly in Q1
18:07
of next year, we will present the top line unblinded data.
18:12
And that's where, you know, that's where we're expecting
18:14
some pretty interesting things. Because if this does line up, if
18:17
we have, you know, if we're able to show target engagement with
18:21
our drug safety profile that's significantly improved over
18:25
what's on the market. We've selected our dose and
18:28
we've shown clinical signal, then I think we'll be ready
18:31
importantly for a phase three registration study.
18:34
So everything's lining up for that, for that kind of reveal
18:37
and Q1. And I think we're all excited to
18:39
see that because if that's the case, then we truly have a, you
18:42
know, best in class and a transformative treatment for
18:45
Alzheimer's disease. Yeah.
18:46
And it, it is, it is super exciting just to sort of rewind
18:50
by a little bit those decisions that you made to have, you know,
18:54
a larger biomarker rich phase 1B study so that you have that
18:58
clinical signal. Was that related into the plan
19:01
to then go straight into, into a pivotal phase three?
19:04
What, what, what, what else really drove that decision.
19:07
I think a couple of things and, and when I came in as CEO and,
19:10
and what what we saw before is companies before us had actually
19:14
run shorter trials kind of faster, a little bit biotech
19:19
mentality kind of, you know, quick and fast and somewhat less
19:22
costly. And a couple of companies had
19:24
done kind of, you know, three months studies, 30 patients just
19:29
looking at biomarkers because you get that early signal in a
19:32
few patients fairly quickly. And we watched kind of those
19:36
companies do that and they got their signal, the biomarkers
19:38
moved Interesting. But then at the end of that
19:41
short study, people were like, what does that really tell you?
19:45
So that, and we saw that happening.
19:47
So we took a step back and said, let's not, you know, fund that
19:52
study or run that study because we're going to end up in, you
19:55
know, kind of no man's land and people are going to say
19:57
interesting, you know, but. So it was a, it was a certainly
20:01
a conscientious decision to to step back and say, look, we need
20:04
to run a study that's going to give us a definitive signal
20:07
here, One that's going to show the community that, you know,
20:10
the pharmaceutical potential partners, the investors that we
20:13
have something truly special. So that means we need to get a
20:15
clinical signal, which means we need to run this over, you know,
20:20
a longer period of time than three months.
20:22
We need at least 12 months to show some sort of clinical,
20:25
clinical benefit. So it was really a thinking, I
20:27
guess several fold band that we wanted to you know, provide the
20:33
opportunity for investors and for for us and for Kols to get a
20:37
fairly definitive result as to whether this antibody was going
20:40
to perform as we expected. And that meant a much more
20:42
comprehensive study. And then the thinking was that
20:46
if we're successful, as I said earlier, if you can demonstrate
20:49
at the end of that study, you've got a clinical signal, you've
20:51
got your safety, you've got your dose, you've got target
20:53
engagement, all those components then make it possible that you
20:59
can step into a phase three registration study.
21:01
So all of a sudden if it, you know, we, we can go from the 1B
21:05
and skip over the phase two, which is several years, several
21:08
$100 million and go straight to a registration study.
21:10
So not only is it a more cost effective development path, it
21:14
gets your drug to market that much faster.
21:16
So I think those two components, you know, can we fund, can we
21:19
invest in something that's going to give us a definitive answer
21:22
and would that actually streamline the regulatory path
21:25
to market kind of really drove our decision a couple of years
21:28
ago on the design of the study? Yeah.
21:29
And it's a, it's a super interesting approach.
21:31
I think there are too many people and too many companies
21:34
out there that will go with what sort of the typical and status
21:36
quo is when it comes to trial design.
21:38
But you know, it's a really in the way that you guys want to
21:42
it. It takes something that is out
21:44
of the ordinary and something that's a bit of a risk.
21:45
And you know, it seems as though, you know, so far it
21:48
seems to be paying off. And I hope that continues.
21:51
It, it does. And it was, it was interesting,
21:53
Ben, that that when we kind of announced that when we came out
21:56
with this is the trial design that we want, you know, we now
21:59
want to fund, and this was a couple of years ago.
22:01
The investors were much more interested in funding that than
22:06
a quick, a quick and dirty study because they understood where
22:09
this could get them. And again, that as as were the
22:11
the pharma companies, you know, we sat down with them and said,
22:13
here's what we want to do. And even they were like, wow,
22:15
that's, that's pretty impressive for an emerging company to step
22:19
into a, you know, quite the comprehensive 1B study.
22:21
You know, we like that. So even our, our discussions
22:24
with pharma over the past, you know, year, year and a half, as
22:27
we've been executing on the study, you know, they understand
22:30
what the potential is at the end of this and what data they will
22:33
receive. And I think they're much more
22:35
interested in that. You know, the challenge, if
22:38
that's the right word, is that it's a longer study.
22:42
So it's a public company. You're kind of, you know,
22:44
you're, you're, you're waiting for news.
22:46
Obviously 12 months is longer than three months.
22:49
And then also it's, it's more costly, You know, 140 patients
22:53
study is more expensive than a 30 patients study.
22:55
But those, as I said, but those two things, but I think that
22:59
the, the pros certainly outweigh the cons.
23:02
And the investors saw that we did the superb financing earlier
23:04
this year. We had the a, a list of
23:06
investors step in to fund the company.
23:08
So I think people appreciate that, yes, it's a little bit
23:11
longer, a little bit more costly, but it's well worth it.
23:14
And if you can then leapfrog over phase two straight to phase
23:17
three, that's a huge cost saving and time saving at the end of
23:20
the day, yeah. Exactly if, if the data supports
23:23
the thesis that you have to jump straight into that registration
23:27
study, what what do you need to be true both from a scientific,
23:31
a clinical and also from an operational perspective?
23:34
Because it's a big job, right? I mean, it is, but it's not
23:37
unprecedented. We're seeing that with
23:38
Trontinamab and Ross. There are, there are companies
23:40
that do this. So we're not, you know, we're
23:42
not wishful thinking that the FDA is going to bless this by
23:45
any means 'cause there is some precedence there.
23:47
But, and, you know, we have the, we have the, the good fortune,
23:51
to put it mildly. I mean, our chief medical
23:53
officer, which, you know, many folks have met out there, Doctor
23:56
Larry Altsteel. And not only is Larry a
23:58
practicing neurologist, you know, having treated Alzheimer's
24:01
patients for years, but he also ran CNS at Pfizer for a number
24:05
of years. So, you know, we have the
24:08
understanding of what's required for, you know, phase three
24:12
registration studies. And, and we've always said that
24:15
if you can kind of refers to what I, what I mentioned a few
24:17
minutes ago, that there's a few boxes you need to check.
24:20
And one of those is, you know, safety, can you deliver the drug
24:25
safe? And we've, I think we've kind of
24:27
checked that box pretty well now not to get too ahead of
24:29
ourselves. Is your drug getting, can you
24:33
deliver enough drug, you know, across the blood brain barrier
24:36
to engage target? Our Phase 1A data showed that
24:39
are we seeing target engagement with biomarker movements and
24:43
we'll see that at the end of the study.
24:45
Can you identify a, a dose And with this is a, you know, we're
24:49
looking at 3 doses in this study.
24:50
So coming out of it, we'll have our dose defined and can you
24:53
show a clinical signal, a clinical benefit.
24:56
And if you can check all those boxes and we should be able to
24:58
check, we should be able to get data that allows us to check
25:01
those boxes and hopefully we do check them all.
25:04
But if you check all those boxes and that's, that's kind of the
25:06
prerequisite for initiating a registration study.
25:10
So a lot of thinking has gone into it.
25:11
And again, there's precedence and benchmarks around, you know,
25:14
these are the boxes that you need to check.
25:15
This is what you need to show. And if you do that, then you
25:20
can, you know, and that's what we'll do.
25:21
We're designing that next study now how that could look and how
25:25
that can run and you know how, how, how the time and the cost.
25:29
We plan on sitting down with the FDA.
25:31
We we were, we received fast track designation from the FDA
25:37
4:00 PM and 3:10 last year. So that allows us to engage with
25:40
FDAA little bit more often, a little bit more readily.
25:43
So we'll sit down and we'll have our end of phase two meeting
25:47
kind of first half of next year when the full data set comes out
25:50
and we'll present that registration study plan to them.
25:54
And we, you know, have high convictions and believe that the
25:57
FDA will seriously consider that to step into a phase three
25:59
registration study. So a lot of thought and a lot of
26:02
expertise, but a lot of thought has gone into that next study.
26:06
And, and are we, you know, being realistic in our assumption that
26:09
a registrational study could follow this 1B.
26:12
And I think we're, I think we're, you know, we're, our
26:14
expectations are, are certainly high, but based on, you know,
26:17
sound expertise and knowledge and certainly precedence that's
26:20
gone on before us. Yeah, super exciting.
26:23
And I think, I think a lot of people are going to be keeping
26:25
their eyes peeled for for that full data coming out in Q1 next
26:28
year. It is and it's, you know, it's,
26:30
it's Alzheimer's disease on top of it.
26:32
Any, any disease is, is important and to itself for
26:35
sure. But I think Alzheimer's is
26:36
affected probably everybody directly or indirectly.
26:39
We hear that all the time. And it's such a challenging, I
26:42
mean anything to do with the brain neurology is, is is very,
26:47
very challenging. And the products that have come
26:49
to market the past, you know, few years with lucanumab and
26:52
donanemab are important steps, but it still shows that there's
26:56
a significant gap and a significant unmet medical need
27:00
with Alzheimer's patients and caregivers.
27:02
So ideally, if we come to market with something that's with much
27:06
better safety profile and improved efficacy profile, that
27:10
would be truly significant, yeah.
27:12
If we quickly then make the the switch over to your other
27:14
venture. So alongside promise you, you
27:16
also lead Mongoose bio. So that's an MD Anderson spin
27:20
out that's focused on next generation TCRT cell therapies
27:23
for solid tumours. What, what essentially attracts
27:26
you to that opportunity and then what what has to change for cell
27:30
therapy to move beyond the hematologic cancers and become a
27:35
serious treatment option in common solid tumours, you know,
27:39
breast, lung, gastric and so on and so forth.
27:41
An. Interesting question.
27:44
I mean, I lived in Houston for a number of years when I was
27:46
running Opexa and met a number of the researchers faculty at MD
27:51
Anderson. And you know, several years ago
27:54
now I reconnected with 1. And I think the thing that
27:57
attracted me, I mean, it attracts me to all opportunities
27:59
is the, you know, certainly the people and, and Doctor Yi,
28:02
Cassine Yi, who's the founder of Mongoose and one of the top
28:06
faculty and top cell therapy clinical oncologists anywhere in
28:09
the world, had been developing the cell therapy for, for a
28:13
number of years, 20 years. And when I was in OpEx a more, I
28:17
guess coincidentally, I was running a cell therapy company
28:20
back in Houston. So I understand the cell therapy
28:22
world very well. And and you know, Cassian was
28:26
given permission to set up Mongoose bio spin it out of MD
28:29
Anderson, which doesn't happen to many of the faculty there.
28:31
MD Anderson recognized the potential in taking this
28:34
externally and setting it up. So I kind of helped him with
28:37
that as well. I think the when I looked at
28:41
Mongoose and the the science and the technology that Cassian had
28:45
developed over the years, again, it comes back to, you know,
28:48
differentiation and I'm very big on, you know, anything I do, you
28:52
know, there needs to be some sort of differentiation
28:54
potential for best in class and and such.
28:56
And when you looked at the cancer therapy to your point,
28:59
and this is next generation cell therapy.
29:02
So next generation car T, this is T cell receptor T cell
29:05
therapy. So I'm going to the details, but
29:06
it's next, next generation cell therapy and what it allows.
29:10
And I think the two challenges and this is what Doctor Yi
29:12
explained to me back in the day, the two challenges to cell
29:16
therapy were identification of novel kind of intracellular
29:21
targets. Cause CAR T only allows for
29:23
targeting the extracellular targets, which limits CAR T
29:27
treatment to less than 3% of cancer patients.
29:30
So there's a whole host of cancer patients that don't have
29:32
access to CAR T because it's very, you know, because they
29:36
don't have novelties intracellular tumor targets.
29:40
So casting over the years with MD Anderson had generated a huge
29:43
discovery platform and identified some really, really
29:46
novel very interesting targets that would be expressed on solid
29:50
tumors. So they, so the novel targets he
29:54
had solved for. And the other challenge that
29:56
cell therapy faces is with T cell exhaustion.
29:59
Typically when you give the immuno oncology therapies,
30:03
there's a, there's a robust cell response, T cell response and
30:09
the, and the cancers go into remission.
30:10
But over 4, six months later, the, the cancer comes back with
30:15
a vengeance. There's a relapse because the T
30:17
cells have become exhausted. So the other piece of the
30:19
puzzle, the other challenge was how to prevent T cell
30:21
exhaustion. And over the years, Cassian has
30:25
developed technology that allows him to reprogram T cells that
30:29
are persistent over time that last for years and keep cancer
30:32
in remission for years. So it was that differentiation
30:35
that I found truly exciting. The challenge with cell therapy
30:39
is that pendulum swings back and forth and it's probably swing
30:41
the other way over the past couple of years.
30:43
There's a lot of focus on manufacturing and CMC and how to
30:47
commercialize and have a, have a, you know, commercially
30:50
feasible product. Cell therapy can be complicated.
30:53
There's a lot of talk about in vivo processing with cell
30:55
therapies and a lot of that. And the team kind of runs I, I
30:58
kind of certainly oversee and help, but the team kind of runs
31:01
that from a manufacturing perspective, there's a lot
31:04
that's been integrated into the platform.
31:06
So there's, there's challenges to the cell therapy world and
31:09
there's, but I think Mongoose has demonstrated again, the
31:12
ability to, to, to overcome those challenges.
31:15
And a lot of what casting has done over the years, you know,
31:18
has been validated in the clinic.
31:20
So it's exciting to think that if we can take that now and put
31:23
it into the clinic with these, with these reprogrammed cell
31:25
tech, reprogrammed T cells with novel targets, I think that has
31:30
huge potential in treating solid tumors.
31:33
Gastric, esophageal lung, breast cordoma is one that we're
31:38
looking at. So there's a number of different
31:39
opportunities there, but it's yeah.
31:40
But cell therapy can be can be challenging for sure.
31:43
Yeah, No, it's. Definitely one of one of the
31:45
harder fields within the industry for sure.
31:48
If we just sort of take a step back here, you know, you've,
31:51
you've built and LED companies across various different
31:54
therapeutic areas, stages of development, technologies,
31:58
geographies, all within the biotech realm.
32:00
When you strip away the science, what are the ingredients that
32:05
consistently separate companies that make it from those that
32:09
don't, all the way sort of from a point of inception through to
32:12
the clinic, through to commercialisation and an
32:15
eventual exit? Yeah.
32:18
I think there's a few components there, Ben.
32:20
I mean, it's kind of the, you know, question that's often
32:22
asked. And I think certainly, you know,
32:25
outstanding science I keep coming back to and we keep
32:27
coming back to this best in class.
32:29
So outstanding science. And I don't, I don't just mean
32:31
kind of clever, cool science. It has to have, you know, has to
32:35
have potential to become commercialized.
32:37
And a lot of interesting science doesn't or it's not obvious.
32:42
So yeah, novel really fundamentally differentiating
32:49
science that can be best in class is probably to me the most
32:52
important. You also want to have people in
32:57
the company that are executing on the on the goals to have
33:01
significant experience in all the and this is even for
33:03
emerging companies, startup companies or late stage, they
33:05
have to have deep, deep knowledge in my opinion, how to
33:09
execute on manufacturing. So CMC is critical pre clinical
33:14
transition to clinical stage regulatory.
33:16
So you need experts around the table that have done this
33:19
multiple times. And I too often do I see people
33:21
that are kind of learning on the go.
33:24
I mean, we're all learning on the go for sure.
33:26
But I you, but if you're going to run CMC, you're going to run
33:29
development, you're going to run the phase one, you have to have
33:31
experience and expertise in how to do this and have have have
33:36
done it several times before, because that's hugely important.
33:40
You know, you also need, you know, you also need kind of
33:43
chemistry among, you know, culture, if you want to call it
33:46
that, or chemistry among the people working together.
33:48
You want these brilliant people coming together, but there also
33:50
has to be a, you know, a fundamental kind of chemistry
33:53
with everybody working together. And you also need leadership.
33:57
So you need leadership in the different functional units.
33:59
You need leadership from your CEO that I think sets the goal,
34:03
you know, three years, five years down the road, but can
34:06
also set the the kind of execution of the plan on how to
34:10
execute to get there. So there's a short term focus on
34:13
what needs to be done to get to that long term vision.
34:16
And I think leadership is an absolutely critical role and we
34:20
don't often see that within companies and we certainly don't
34:23
often see that kind of chemistry.
34:25
But I think those are absolutely fundamental.
34:28
The other component that I truly value, we don't whether it's
34:31
100% necessarily necessary, I'm not sure, but I certainly
34:37
believe that. And I've kind of patterned my
34:39
life or career after that is being able to leverage different
34:43
geographies, being part of my attraction to wanting to run a
34:46
China based company or a South Korean based company was being
34:51
able to leverage, you know, technology, capital, people from
34:57
different parts of the world. I mean, there's two objectives
34:59
to that. One is I have a true belief that
35:01
anything I do, I want to provide drugs to people globally, all
35:05
over the world, not just the US. They have to be, it has to be
35:07
drugs available to everybody around the world and at
35:10
affordable prices. But in kind of maintaining that
35:13
vision, there's also a ton of value that can be extracted or
35:16
leveraged from, you know, Asia working with US.
35:19
And that's why I said, if you can bring those two countries,
35:22
you know, China with US or South Korea, Japan, and leverage those
35:26
opportunities, you can create so much more shareholder value on
35:30
route to your providing drugs globally.
35:32
And I think that's a challenge that's not always picked up on
35:36
for U.S. companies. And I've been fortunate and
35:38
honored to be, you know, being asked to run companies around
35:41
the world. But I think if, you know, even
35:43
in start up stages and we're doing that, you know, we're
35:45
certainly thinking about that a promise, we're thinking about
35:47
that a Mongoose how to leverage global collaborations and
35:50
capital and such to build a, you know, it sounds a little bit
35:53
high and mighty to build a global corporation, but that's
35:56
truly tons of value there in addition to getting the products
35:59
to to patients around the world. So I think there's a few
36:02
components that have to get come together to make to make
36:05
companies successful. Yeah.
36:07
And I think your perspective on that is going to be particularly
36:10
useful to anyone who's sort of stepping into that leadership
36:13
role for one of the first times. And yeah, I think your career
36:16
and your perspective is definitely one that can be
36:19
learnt from. Just to sort of wrap things up
36:20
then, Neil here. If you could have dinner with
36:24
any scientist during Innovation Park or present, who would it be
36:26
and why? That's an interesting question
36:29
you guys kind of asked and it's, you know, you kind of think
36:32
about it a little bit and there's tons of people would be
36:35
interesting to the one that kind of came to mind because it's
36:37
very, it's kind of very, you know, interesting to me.
36:40
And one that kind of goes back a number of years when I was
36:43
studying and it's relative and it was, it was instrumental in
36:46
me kind of loving the whole field of neuroscience.
36:49
And he's, he's probably the, the, the, the father of
36:53
neurology. And it's a name you don't hear
36:55
that often, but I remember reading all of his books and
36:58
looking at all of his drawings. And it's a, it's a physician by
37:01
the name of Ramon Kahal KAJALA, Spanish neurologist back in the,
37:07
I think it was the late 1800s. But I remember when I was
37:10
studying at university and reading, you know, all The
37:13
Pioneers of neurology. And Ramon Kahal was somebody
37:17
that just fascinated me because I can still picture the hand
37:20
drawings of the, of the neurons in the brain.
37:23
And he was really the one that taught us that the brain was
37:26
comprised of individual cells. I think before him, we all, we,
37:30
I mean, the, the thinking was, was a massive web of some, some,
37:34
some mass. But he, through the staining and
37:38
the Golgi staining of cells was able to kind of differentiate
37:41
the, the different neurons. And it is, I can remember
37:44
looking in the in the textbooks of the hand drawings of the
37:47
neurons that he started to build a concept of the brain and teach
37:51
us how the, you know, the connectivity and how the
37:54
communication among cells in the brain was taking place.
37:56
So really somebody that I thought was really, really cool
37:59
looking at the drawings and somebody that I read a lot as I
38:02
kind of, you know, kicked off my whatever young neuroscience
38:05
career. So that would be a fascinating
38:06
person to sit down with him and, you know, right when the brain
38:09
was being discovered and articulated, kind of what he was
38:13
thinking and then, you know, see what he would think about where
38:16
we've come today, if in his mind we've come that far or not very
38:19
far, we've made leaps and bounds or not really.
38:22
So that's somebody, as I said, there's a number of them.
38:23
That's somebody that I thought would be kind of interesting for
38:25
sure to to sit down with and and pick his brain, so to speak.
38:29
Yeah, 100%. It's not an answer I've had
38:31
before, but I think I think it's a great one for sure.
38:36
But look, it's been been an absolute pleasure to have you
38:38
join me today. I really appreciate you taking
38:39
the time. Well, thanks very much, Ben.
38:41
As I said, I'm, I'm happy to talk about, you know, good
38:44
science and we've got great teams and great people doing
38:47
some, you know, some very important work for, for the
38:50
patients and the caregivers around the world.
38:52
And as I said, we'll see and you know in Q1, in a matter of
38:55
months from now, whether you know, PMN 310 lives up to all
38:58
our expectations. We, we hope and think it will.
39:00
So it'll be an exciting, it'll be an exciting number of months
39:02
and a lot of, a lot of preparation ahead for the, for
39:06
the promise team. But man, I really, really
39:08
appreciate you taking the time to allow us to, to tell the
39:10
story. Thank you.
39:11
Yeah, of course. And fingers are staying crossed
39:13
for you for the next next few months.
39:16
Appreciate that. Thanks very much.
39:18
No worries at all and thanks for everyone for tuning in.
39:20
Make sure you drop a like and subscribe to the Biohub page.
39:24
There will be plenty of episodes to come, but for now that's all.
39:27
Thanks a lot. Bye, bye.