Aldevron
Duration: 21:19 Min
From Sequence to Vial: A Seamless RNA LNP Manufacturing Solution
Transcript
0:01
Yes, I'm happy to be here to talk RNA, LNP,
0:03
end-to-end sequence vial with Scott.
0:07
Mark Wetzel here.
0:08
I'm a 23-year veteran of Danaher,
0:11
and I thought I'd start a little bit with,
0:16
you know, just some thoughts around Danaher
0:18
and some things we're good at.
0:19
And Danaher's good at a number of things,
0:21
M&A, running businesses.
0:23
We have some great leaders,
0:24
but there are two things that I think
0:26
really sort of differentiate us.
0:27
One is DBS, our business system.
0:31
We talk about that a lot.
0:32
It's our engine for continuous improvement.
0:37
And it is based on the Toyota production system.
0:41
It's not unlike Six Sigma,
0:43
but it's the culture that threads
0:45
all of our companies together.
0:46
And what's different about it is our discipline
0:50
around applying it and living and breathing it
0:52
every day from top to bottom in the organization.
0:55
And also what it is, and we don't talk about this a lot,
0:58
in addition to the foundation of lean
1:00
and the Toyota production system and continuous improvement,
1:03
it's also the toolkit that we talk about
1:07
is a collection of best practices
1:09
that Danaher has acquired over 40 years
1:13
and hundreds of acquisitions.
1:15
Because what we're really good at
1:16
is identifying a best practice in a business
1:19
and carving it out, turning it into a tool,
1:22
deploying it to all our other businesses, right?
1:24
And that's one of the ways that we maintain consistency
1:27
from business to business
1:28
and how we're all more or less being run in the same way.
1:33
So that's one thing.
1:34
The second thing is the networking that's available
1:37
in the portfolio and the family of companies, right?
1:39
And how we help each other for the benefit of clients.
1:42
And there's no better example of that
1:44
than what we're doing here today with this event.
1:48
But it's two things that I think are important
1:51
and I'll explain why I bring those two things up.
1:54
For one, when we talk about Aldevron,
1:57
for those of you that are familiar
1:59
with the Aldevron business,
2:01
it's a different business today
2:04
than it was three years ago
2:05
when Danaher acquired that business.
2:08
And partially the reason is that
2:10
this DBS continuous improvement system is alive and well,
2:15
driving really breakthrough improvements in the business
2:17
and things that are material like on-time delivery
2:20
and lead time reduction and quality improvements
2:23
and customer experience, right?
2:24
So it's really a different business
2:26
than it was even three years ago, even one year ago,
2:29
for those of you that are familiar with Aldevron.
2:32
Second reason I bring that up,
2:33
this idea of the network and the way that OPCOs
2:37
or OPCOs and the Danaher family
2:39
work together for client benefit.
2:41
This couldn't be a better example
2:43
of how we've made that happen.
2:45
What Scott's business, the Cytiva Nanomed team
2:48
and the Aldevron team has built
2:50
into an end-to-end sequenced vial RNA LNP offering
2:55
that we believe is best in class.
2:57
And we're really in a privileged place because of that.
3:02
That makes sense.
3:07
So you may have seen some of these,
3:10
how am I doing?
3:19
This may be a slide that you've seen today,
3:20
but it is a one-pager that sort of lays out
3:26
how we connect the dots
3:28
between all of our Danaher businesses
3:30
and the ways we interact with clients
3:32
to accelerate LNP for RNA development and manufacturing.
3:35
So you've got the steps in the timeline
3:38
and the development process.
3:40
You've got swim lanes down on the left
3:43
and the Danaher portfolios
3:45
that are represented,
3:48
where the offerings fit into the workflow.
3:55
And of course, Scott and I are going to talk
3:57
about that bottom swim lane of services together here.
4:02
But important to point out that for us at Danaher
4:07
in this space, we feel like we are,
4:11
I'm going to steal one of Scott's guys' terms here.
4:14
We're an incubator for optionality.
4:17
We've got a lot of different options available
4:19
to solve the same problem.
4:22
So we have operating businesses,
4:24
Cytiva, Aldevron and others.
4:27
We have very complementary offerings,
4:30
but we also have overlapping offerings in some cases.
4:34
And we also have occasions to work with competitors
4:38
of Danaher businesses when it makes sense,
4:40
again, with the client in mind.
4:42
But the key here and the takeaway is we all know
4:45
how to wear the Danaher hat when we need to.
4:55
So our end-to-end sequenced vial offering
5:00
in Fargo, North Dakota, where Aldevron is based
5:05
is a workflow business that simplifies logistics
5:11
and eliminates timeline risk.
5:13
Full stop, that's the key value in what we're offering.
5:18
We, of course, can handle all of these pieces,
5:22
but the key benefit is removing shipping time.
5:27
Most of our clients are using multiple partners
5:31
or sometimes multiple sites with the same partner.
5:36
And what they are doing is, you know,
5:40
multiple tech transfers in their process.
5:44
With Aldevron and in Fargo, we, and I would call that,
5:49
many of our competitors, sort of a collection of parts
5:53
versus what we have at Aldevron,
5:54
which is a true workflow business from sequence to vial.
5:59
And we are the only ones in the market that I'm aware of
6:03
that have at the front end,
6:05
the capabilities of Precision Nanosystems,
6:08
now the Nanomed team at Cytiva,
6:11
where they're working on LNP and they can provide lipids,
6:15
they can provide formulation and particle design,
6:18
and also a proprietary encapsulation platform.
6:22
And with that strength of competency, you know,
6:27
provided in this solution in a seamless way,
6:30
we think we have a winning proposition here.
6:35
So Aldevron, for those of you familiar, well-known,
6:45
it's the gold standard in nucleic acid production,
6:48
very well-known for plasmids and DNA production,
6:52
25 years GMP experience.
6:55
We've done 5,000 GMP DNA batches and 165,000 batches,
7:02
if you include research grade,
7:04
which is sort of mind-boggling.
7:07
So well-entrenched in that space.
7:09
What is less known about Aldevron
7:12
is how competent and experienced we are in RNA.
7:16
This year, we will have produced 120 GMP RNA batches
7:23
for clients in phase one, two, three,
7:26
commercial programs with PPQ.
7:29
Our first RNA batch was in 2017.
7:34
We have a robust quality system,
7:36
and we'll talk about analytics and quality
7:39
in a bit more detail later.
7:42
An analytical testing panel with sterility and potency,
7:47
21 CFR compliance.
7:49
And this year we produced our first drug product batch
7:52
in Fargo in January with the help
7:55
of the Cytiva Nanomed team.
7:58
We're producing our second GMP batch next month.
8:01
And if you combine that with the experience
8:03
that they have in the Vancouver operation,
8:06
where they've produced three GMP drug product batches
8:10
end-to-end, you can see our trajectory
8:13
and experience is climbing.
8:16
We also have two client programs signed on board
8:21
where we plan to deliver GMP material
8:25
for their clinical programs in the first half of next year.
8:28
So our competence and experience
8:31
is definitely growing here.
8:33
This is a high-level process map.
8:43
Couple takeaways here.
8:45
Our preference for hardware consumables
8:49
and reagents is clearly Cytiva.
8:51
We've got some sole source hardware mitigations
8:56
throughout our operation,
8:57
but predominantly that's our preference.
8:59
Cytiva is our partner.
9:06
We have strong analytical and regulatory support.
9:10
With analytics, our team is very experienced
9:15
in things like multi-analyte detection,
9:18
as well as antibody conjugates.
9:22
And if you combine the experience of the Aldevron team
9:26
with the 20 years of LNP-focused analytics experience
9:31
with Scott's team in Vancouver,
9:33
this is really a good example of one plus one equals three
9:37
to the benefit of our client
9:38
in the analytics space for sure.
9:42
From a quality standpoint,
9:44
we have an experienced regulatory team
9:47
that has experience filing INDs on behalf of our clients,
9:52
but also can help with regulatory guidance
9:56
from start to finish
9:57
and help our clients define their regulatory pathway.
10:01
We are also well audited.
10:04
We passed an FDA site inspection less than three years ago.
10:10
We have a client audit almost every week,
10:16
Danaher GMP audits.
10:18
When we launched our drug product offering,
10:20
we also conducted a simulated FDA inspection
10:25
with a team of 20 year FDA former auditors.
10:30
We were hard on ourselves.
10:32
We had a couple of gaps that we have since closed
10:38
since that time in January.
10:40
So we have a high level of confidence
10:42
around our regulatory compliance in our site in Fargo
10:46
as a result.
10:49
Thanks for joining everybody.
10:51
Scott's going to talk a lot more about this,
10:53
but yeah, I don't want to steal his thunder
10:58
other than to say that our aspiration at Aldevron in Fargo
11:04
is to be the world's leading CDMO, LNP provider
11:11
on the NanoAssembler NextGen platform.
11:17
And we believe in the promise of the systems.
11:21
We think that Danaher and Cytiva's investment
11:24
in the innovation and the architecture of the new GMP system
11:27
that you can see in the middle of the screen there
11:29
is pretty special.
11:32
Scaling up, scaling out, repeatability,
11:36
cost of consumables coming down.
11:38
We're really excited about this.
11:39
It was just launched this year.
11:41
We have two of them in Fargo
11:43
and we've provisioned and qualified these instruments
11:47
and we're ready to roll.
11:48
And the GMP run that we're planning next month
11:50
is going to be on that equipment.
11:59
Yeah, so all that said about Cytiva
12:05
and beating the Cytiva drum,
12:07
we also know that we have to have a platform,
12:10
an LNP platform agnostic strategy.
12:13
In addition to offering the Cytiva solution,
12:17
we also entered an agreement with Acuitas this year,
12:20
well-known in the industry, and ran a pilot.
12:24
We are certified on their tech
12:26
and we are now a preferred CDMO partner
12:29
that they are now recommending to their licensed partners.
12:32
So we're happy and having conversations
12:35
with those clients today.
12:36
So it's opened up another avenue
12:38
it's opened up another window of opportunity for Aldevron.
12:43
As we have become familiar with this microfluidic platform,
12:49
we have also provisioned an off-the-shelf
12:51
generic T-Mix platform
12:54
that we also are now provisioning in GMP.
12:56
It's a Knauer-based platform.
13:01
And again, we have clients with that preference
13:04
and it opens up even more opportunities
13:07
for the Aldevron business.
13:09
So if we profile opportunity funnel,
13:12
we have those that are on the PNI platform,
13:14
we have clients that are licensed with Acuitas,
13:18
happy to talk to them.
13:19
We have folks that are just on a generic
13:22
T-Mix microfluidic platform and we can talk to them.
13:27
And then there's the rest of the opportunities
13:31
that are on more or less a proprietary platform
13:34
of their own or something else.
13:38
And we're opportunistically speaking to those folks as well.
13:47
We have analytical platforms well-defined
13:52
for both drug substance and drug product.
13:55
And by doing this
13:57
with the most up-to-date regulatory guidance,
14:01
to me, this is the way that we best operationalize
14:04
the promise of our end-to-end solution.
14:09
Fancy way of saying maybe that when we have clients
14:12
that are using multiple partners or multiple locations,
14:15
the place, the bottleneck or the pain point
14:17
often is the analytics or the acceptance criteria
14:21
for moving from one place to another.
14:23
At Aldevron, in our solution,
14:26
it's the same methods performed by the same people
14:30
in the same location in an optimized way.
14:33
So you can imagine the way that we're shrinking the timeline
14:36
just by having this in place with our teams.
14:44
So it's pretty important for us.
14:47
And of course we do product-specific development
14:49
as required from clients.
14:51
And this isn't a comprehensive list.
14:53
There are compendial assays not included,
14:57
pH, endotoxin, et cetera, et cetera.
15:04
A quick moment on something we're really excited about.
15:06
We've entered into an agreement with a company called Codexis
15:12
and obtained an exclusive license
15:15
for their Codex high-cap RNA polymerase.
15:20
This is an enzyme that has a lot of promise
15:24
and there's a lot of excitement around this.
15:26
There are three key benefits of this enzyme.
15:30
There are three key benefits of this enzyme
15:33
that we will use both for our internal manufacturing,
15:36
but also for global supply.
15:39
Significant cost savings
15:41
because it produces 95% capping efficiency.
15:45
There's an up to 62% lower requirement for clean cap.
15:51
It's a really expensive reagent
15:54
and that's really a significant savings to clients.
15:57
Yeah.
16:01
In my experience, even worst case,
16:03
my rationale of capping,
16:06
I never got less than 90%.
16:08
Okay, we're-
16:09
So, I'm just curious,
16:11
this 62% might be used for another method.
16:15
That is really low.
16:17
Really low?
16:18
You think it's conservative?
16:25
We have some experts out at the table here.
16:28
I think that the efficiency,
16:30
he's talking about the efficiency is over 95.
16:32
But the use of the clean cap is 62%.
16:39
I never got below 95%.
16:43
Capping efficiency?
16:45
Yeah, capping efficiency, 95%.
16:51
Well, because-
16:53
Yeah.
16:54
I'm just curious, how come?
16:57
I think it means that you don't have to use
16:59
as much clean cap, right?
17:00
Right.
17:01
If I understand it correctly.
17:02
Yes.
17:03
You can use much less clean cap
17:04
because efficiency is already very high.
17:07
It's clean, if I understand it correctly.
17:09
Yes, because this enzyme improves
17:11
the capping efficiencies to 95%,
17:14
which we see repeatedly.
17:18
Okay, yeah.
17:19
Let's take it offline.
17:20
We can talk more about that, for sure.
17:24
And of course, optimal manufacturing
17:26
has a second benefit: higher yields
17:28
and integrity, even with long, complicated transcripts.
17:32
But most importantly, the safety profile.
17:35
We see significantly less immunogenic
17:39
double-stranded RNA produced.
17:48
The SA25 is an acquisition of Cytiva,
17:50
a company formerly known as VanRx.
17:53
Really innovative aseptic isolator approach
17:59
using software and robotics to minimize human intervention
18:06
while providing a lot of flexibility
18:08
and things like bioburden.
18:09
This instrument can fill syringes as well.
18:14
For us, we have it qualified and ready
18:19
through media fill and CCIT for 2R vials, 10R vials.
18:25
And we're using the shot vials, Diokyo caps,
18:29
AR, Raymond, life caps for 10R vials.
18:33
Our current scale is 4,800 vials, 2R,
18:36
or 2,300 vials for 10R, but we have plans
18:39
to expand this from what is two carousels
18:42
to five carousels and multiple shifts
18:45
that get us to almost 10 or 12,000 vials.
18:48
And that's planned in the next year.
18:49
So we're planning on scaling this,
18:52
but we're happy about this instrument
18:54
and what it provides for us.
19:03
This is a represented pressure-tested timeline,
19:09
a managed timeline that our clients really appreciate
19:12
when we're sort of level-setting expectations.
19:15
They appreciate the thought and the detail
19:17
that we've provided here all the way
19:19
into the phase and the workflow,
19:22
how long things should take in a managed way.
19:27
But importantly, this also calls out
19:30
what we feel is a really differentiated capability
19:34
at Aldebaran, and that is our program
19:36
and project management capabilities.
19:39
We think we have a best-in-class team,
19:42
highly engaged and efficient,
19:44
and working directly with clients
19:46
and pretty effective.
19:52
It's just a case study of our pilot program this year.
19:55
I'm not going to spend too much time
19:56
on this in interest of time.
20:00
This is a represented pressure-tested timeline, a managed timeline, that our clients really appreciate when we're sort of level-setting expectations.
20:15
They appreciate the thought and the detail that we've provided here all the way into the phase and the workflow, how long things should take in a managed way.
20:28
It's just a case study of our pilot program this year. I'm not going to spend too much time on this in interest of time.
20:54
Last slide for me is just a picture of our world-class breakthrough campus in Fargo, North Dakota. This is a facility that we're quite proud of. And we're happy to have clients and partners visit and take a tour. And it's a really, it's a gem for us. And we're excited about it.
21:19
Sort of happy and lucky to be able to work in this facility. There's nothing like it. And that's it for me. Sequence to vial.