Latest / The BioHub - by Avetix / Episode 213 - Fred Aslan - CEO Artiva Bio

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Episode 213 - Fred Aslan - CEO Artiva Bio · The BioHub - by Avetix

0:06
Welcome back to another episode of the Bio Hub and Avetix
0:09
Podcast. Today I'm joined by Fred Aslam,
0:12
CEO of Artiva Biotherapeutics. Fred has spent more than two
0:17
decades across VC, biotech and company leadership.
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Throughout his career, he has been involved in the creation
0:24
and growth of multiple successful companies, including
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Receptors and Vivian Therapeutics.
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Now he's at Artiva, which is a clinical stage company
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developing off the shelf NK cell therapies.
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And in this conversation, we discussed Fred's journey from VC
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into operating roles, the evolution of Artiva, lessons
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from fundraising, leadership and what the future holds for cell
0:48
therapy. Pleasure to have you, Fred.
0:50
How are you? Great.
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Thanks for having me Max. And some people might have seen
0:55
across LinkedIn as well. I, I was lucky enough to be with
0:58
Fred on site in Artiva in San Diego a few weeks ago.
1:02
So coming off the back of that, I feel pretty excited to have
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you here for sure. I'm excited to be here also.
1:11
So, yeah, I, I want to start with with you and your
1:13
background. So you, you, you've had a pretty
1:15
unique career. You know, I I talked about VC
1:18
entrepreneurship and company leadership.
1:21
Looking back, how did that journey unfold and what
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ultimately drew you towards operating roles?
1:29
You know, in many ways, and I think it's hard when you start,
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you don't really know a lot of the different options out there
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unless you have, it's very hard to know.
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I started going to medical school and then in medical
1:42
school is when I realized that I was a lot more intrigued about
1:45
than necessarily choosing A specialty that then I'd be
1:49
practicing for a long time. So I was able to do that
1:52
transition by working at BCG. You know, so while at BCGI first
1:58
learned about investing and, you know, the life cycle of
2:00
companies. That's when I decided to go to
2:03
Business School and then to go work in venture capital.
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You know, venture capital was wonderful.
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I learned so much. I have to say that it was a very
2:11
important pillar. You know, a lot of what I do
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today, I, I do it the way I do because I have that investing
2:18
background. And then while I was in venture,
2:21
I realized that I was really excited about being on the other
2:24
side of the table, not listening to pitches, but actually putting
2:28
on the construction hat and trying to build things myself.
2:31
So because my career trajectory was not linear, so to say, I
2:37
mean, it looks linear in retrospect because every step of
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the way you're learning something that then is very
2:42
relevant for your next role. It didn't feel linear when I was
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going through it. So my advice is always that you
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should do whatever you're really excited to do with people you're
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really excited to do it with because you just don't know
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whether that's actually your final destination or just
3:01
another station on the way to where you're going.
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So by in many ways not settling, by just, you know, searching for
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that thing that I felt was what I wanted to do, it always kept
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me excited, grateful and motivated for what else would
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come. So I feel really grateful for
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that, yeah. You just talked about then as
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well that your VC background really does influence the way
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you work as as ACEO. So how was that?
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How has that experience as an investor really shape the way
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you think about fundraising and building companies in comparison
3:38
to what you know someone else might do?
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You know, I, I think that there are two or three things that I
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would point out. The first one is when you're,
3:48
when you're investing, you need to be very attuned to the
3:52
competitive landscape, right? Because in many ways, what a
3:55
company is trying to do is particularly relevant if you
3:59
really understand what the competitors are actually doing,
4:03
because that's how you define whether they're going to be able
4:06
to thread the needle in a way that will allow them to
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differentiate themselves from the competitors or not.
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I find that it's very easy as ACEO to just swim in your lane
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and not care about what's happening in other areas.
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But but that's also to your disadvantage because there is so
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much pivoting that is natural to happen in the life cycle of a
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biotech company. And we'll talk about Artiva.
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And certainly that was true in Artiva, particularly given how
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how crowded the field has been that by being very, let's say,
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focused on understanding what your competitors are doing, why,
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how are they playing to their strengths and how do you play to
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your strengths. Yet at the same time, having
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differentiation has been really helpful.
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The second thing I would say is because I was on the other side
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of the table, I have a good understanding of what investors
5:00
are trying to understand in that 30 minutes hour that I have with
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them. You know, because I do follow
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the competitive landscape so closely, because I know the
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types of things that investors would have learned as they are
5:14
watching this field from afar. It gives me a sense of where I
5:19
should spend my time because I know those are the things that
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will move the needle in terms of how they think.
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And maybe the third thing is when you invest, particularly as
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a venture capitalist, you generally take board seats.
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And this dynamic of CEO to board is one that is not so intuitive.
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There aren't that many examples professionally where you see the
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same relationship that ACEO has to have with his or her board
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because what is that relationship, right?
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In some ways, they're not your boss yet they have the power to
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hire you and fire you. They're not in the weeds, but
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yet they have to vet all the plans that you're making.
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So it was actually very beneficial for me to have been
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either a board member or an observer in almost a dozen
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companies because I had a chance to see what CE OS had a good
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constructive relationship with their board versus the CE OS
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that did not. So in many ways, I learned a
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lot. And I'd like to think that the
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relationship that I have with my board is based on some of the
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best practices that I have seen. So those are three unique things
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that I don't think I would just have learned on my own or I
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would have learned a lot slower had I not done investing before.
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Yeah, I think they're all really vital.
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I mean, that second point is always really interesting as
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well. You know when you've got 30
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minutes to an hour with these people and you know the way
6:48
they're thinking, how are they thinking in comparison to what
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an operator might think they want to hear?
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I go back to two things. One is there, there, there are
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two things that I would say are the two things that I felt I
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spent most of my time thinking about when I was investor.
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One I already mentioned, which is the competitive intelligence
7:10
piece, right. So when I was trying to
7:13
understand the competitive landscape, because generally
7:15
most exciting areas have a lot of different players that are
7:18
trying to have an impact on that area.
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So when ACEO is attuned to what everybody else is doing and they
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helped me in my education to understand what specifically
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they were doing versus the others as opposed to CE OS that
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just brushed off the competition and just wanted to talk about
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what they were doing. I felt that it would increase
7:40
the the barrier for me to get up to speed with the story because
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you really do need to and the competitive landscape to feel
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very comfortable with a particular story.
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The second is risk, right? Because in many ways you need to
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identify what are the biggest areas of risk.
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If an investment is not going to work, why is it likely not to
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work? And how do you try to do
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diligence those areas so that you feel confident about the
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risks that you're taking? So as ACEO, if you know and
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you're self aware of the areas that actually pose the biggest
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areas of risk, you actually have an opportunity to help the
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investor through that due diligence process.
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You can provide the types of information in a targeted way
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that allows them to get more up to speed as they are trying to
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do their due diligence into these areas.
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So a combination of those things just allows you to make that
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conversation more constructive, like you're all working towards
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a specific outcome rather than you're just pitching the story
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using the same slides and using the same messages.
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Yeah. You're almost thinking I'll give
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them all the information so they're going away from this
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conversation with, you know, no questions on their part.
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Yeah, my, my goal is that whatever information gaps they
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have that I fill, not that I want to get across these 10
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messages no matter what, because it doesn't matter if I get 10
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messages across. But I haven't actually answered
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the questions that they're interested in, so I try to be
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very sensitive to that. Yes, you generally start with an
9:21
overall framework of what you want to cover, but you do
9:24
yourself a disservice if you don't try to understand early in
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the conversation the areas that are of most interest or concern
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to the people with. Yeah.
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And now we're we're you're Artiva.
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What initially attracted you to our TV?
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Like what opportunity did you see when you first became
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involved in the company? I joined the company, I had
9:46
never worked in cell therapy was just the degree of efficacy that
9:51
we were seeing. I mean we have to recognize that
9:54
Auto Car T is probably one of the biggest innovations that we
9:57
have seen over the last decade in biotech, right?
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I mean, we're talking about Auto car T being able to extend
10:05
survival from, you know, as little as six months in some
10:09
indications to five years plus, right.
10:12
And so I was attracted to the notion that, you know, what
10:16
Artiva was doing was actually more about execution than it was
10:22
around biology risk. So let me take a step back.
10:25
You know, the way auto part T works is it's all about
10:29
depleting the specific cells, killing all of the cells that
10:33
are causing the pathogenesis, whether it's AB cell that causes
10:37
cancer or AB cell that's driving autoimmune disease.
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The goal is to kill every B cell.
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The problem with auto car T is the fact that it's, it's less of
10:46
a drug and it's more of a procedure, right?
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It looks a lot more like a bone marrow transplant than it looks
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like a drug, something that's available off the shelf that you
10:57
can just administer, that you can manufacture at scale, so on
11:00
and so forth. What I saw in our NK cell
11:04
therapy was a, A cell therapy that looked like a drug.
11:09
It could be off the shelf. It could be manufactured cheaply
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and had a lot of scalability. And So what we needed to show
11:17
early on was that we could drive a level of B cell depletion that
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was in line with what auto car T was doing.
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And it seemed like that was going to be very possible given
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the additional data from our peers that were being generated
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at the same time, right. And so I like the construct of
11:38
this, this story and challenge being 1 of execution.
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Can you take that biology that is well understood and actually
11:47
design that product that can provide again, access, cost,
11:52
community setting, etcetera. So that was actually very
11:55
attractive to me because in many ways, I think that broadly
11:59
speaking, you know any biotech company, you're going to be
12:03
looking at biology risk and you're going to be looking at
12:06
execution. And the weight of these things
12:08
are very different depending on the story.
12:10
Some biotech companies are all about the biology risk, meaning
12:13
you have to run the experiment. You have no idea if it's going
12:16
to work or not, but if it does, everything else in a way works
12:20
out. Whereas there's other areas
12:22
where you already feel very confident about the biology, but
12:26
it's about the execution. Can you get to market faster
12:28
than others? Can you generate the data you
12:31
know in the right setting? Can you look for the right
12:34
endpoints and have the right regulatory discussions so you
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can be more efficient about the development?
12:39
So those aspects were attractive to me as we started on that
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journey, though there were a lot of pivots along the way.
12:47
Yeah. I can imagine.
12:50
I actually want to ask about the main pivot right into
12:54
autoimmune. I don't know if you just want to
12:57
take it away and just go through the decision making and and the
13:01
journey behind that. Yeah.
13:03
So you know, when I started, which was 2021, there was no
13:08
evidence that deep B cell depletion in autoimmune disease
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would actually work, right. So most cell therapy was
13:16
actually focused on the same indications where auto CAR T had
13:21
actually demonstrated activity. So back to what we were talking
13:23
about before, it was this notion of execution.
13:28
Can you actually demonstrate a similar level of efficacy,
13:31
better, better safety profile and move pretty quickly given
13:36
it's a pretty crowded field? But then what happened was Auto
13:40
Car T started to move very quickly from late line to second
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line. And because a lot of the
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alternative approaches, the allogeneic approaches were
13:51
coming in like 5-10 years behind, it was very difficult to
13:55
contemplate how you could get to market and be able to compete
14:00
with auto Car T because at that point, Auto Car T would have
14:02
already moved to second line or first line.
14:07
There was also a lot of backlash in the sense that the data from
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many of my peers were not showing auto part T like
14:14
effects. And so there was this cloud that
14:17
started to generate around, you know, allogeneic cell therapy
14:21
pharmacology. And towards the end of 2022,
14:24
George Shet, an academic in Germany demonstrated that you
14:28
can actually use auto part T with the same mechanism of B
14:32
cell depletion to actually drive significant improvements in
14:36
autoimmune disease. So it was one of those decisions
14:40
where you're looking at the headwinds ahead of you because
14:44
many are questioning the role of allogeneic cell therapy in
14:47
cancer. And the field remained really
14:50
crowded to this brand new opportunity where again the
14:54
biology risk seem to have been addressed by this proof of
14:57
concept with auto car T and where again on the execution
15:00
side, if we could pivot there very quickly, if we could be
15:04
smart about choosing the right indications to go after that
15:08
play to our strength, then we could stand out as an allogeneic
15:12
cell therapy company going after an area where we could have a
15:15
lot of impact. I love how decisive you guys
15:19
were on that. It was like decision made, this
15:22
is happening, it's how quickly can we do it and not lose any
15:26
ground. I think that's the best part
15:29
about that, that story. You.
15:30
Know as I, as I think about that comment, you know, I have to say
15:33
that had had George Shet's data come out, you know, in the
15:39
middle of 2021 or late 2021 when our entire field still had a lot
15:46
of wind behind its back and we were all still enthusiastic
15:49
about the opportunity in oncology.
15:52
I just don't think they see people pivoting so quickly.
15:55
And I'm not sure that that would have been a decision that I
15:58
would have done at the time, right?
15:59
Really time we were still very focused on the opportunities on
16:03
college. Again, back to what we were
16:05
saying before, when you're following the competitive
16:07
landscape very closely, you sort of realize as you go into 2022
16:12
that this is going to be a big uphill battle and you're
16:15
beginning to have existential questions about what you're
16:17
doing. So there's nothing better than a
16:21
great new path that manifests itself at the time when you're
16:26
having existential questions, right?
16:29
You see this a lot with biotech companies that end up in
16:31
licensing another asset, right? Those are other examples where
16:36
they're having a existential moment and then all of a sudden
16:39
they find an asset that they say, you know, we have the team,
16:42
we're excited about this, we can go forward.
16:44
So again, I would say that I am grateful that at the same time
16:48
as we were having existential questions, this great
16:52
opportunity came along. And you know, credit to my team,
16:55
we did not hesitate. We just jumped all in.
16:58
And it wasn't easy, right? Because when you think about it,
17:01
right at that moment, everybody that was employed at Artiva had
17:05
joined Artiva to cure cancer, right?
17:08
And then one day you're speaking to the whole company.
17:11
OK, guys, guess what, we're going after autoimmune disease,
17:14
right? So it's, it's, it's not easy.
17:17
And I am actually really proud of how well the organization
17:21
adapted. And I think it comes down to the
17:23
fact that people want to help other people.
17:26
They want to develop meaningful drugs.
17:28
And you know, if the opportunity is in cancer, we all have a lot
17:31
of stories that actually attack to cancer.
17:34
But you know what, if there's another area of great unmet
17:36
need, then let's go do what it takes in order to bring that
17:40
impact. You know, so I'm really proud of
17:43
how the organization adapted to all this.
17:46
You should be. I think that's a really nice
17:49
part of it, you know that. And also I think it says a lot
17:53
about you as a leader and the leadership team that you can
17:56
make a decision like this and just the trust of the company
18:00
will go well, that's the right move.
18:02
Then that's where we're going and just just go with you on
18:05
that. I love that part as well.
18:09
Just just for the for the listeners who might not know art
18:13
either, what what makes your approach to NK cell therapy
18:16
different? Yeah.
18:19
So as we were talking about before, the limitations of auto
18:23
car T is that it's a procedure. It is, you take a patient's
18:30
cell, you engineer it, and then you give it back to the patient,
18:33
right? So it's not a scalable process.
18:36
You can try to do it massively parallel, which is what they're
18:40
trying to do, but it has that limitation of scalability.
18:44
The second big limitation is that it comes with very
18:48
significant side effects that actually really mostly require
18:52
that patients are hospitalized during the first 30 days when
18:56
they are receiving the therapy, right.
18:58
And So what our cell therapy is able to do is we're able to
19:02
drive a really deep level of depletion like Autoparty can do.
19:07
Our cells are very scalable. We source our cells from
19:11
umbilical cord units and from one umbilical cord unit, right?
19:15
And there are hundreds of thousands of them banks from one
19:18
umbilical cord unit. We could treat 500 patients.
19:21
And the cause for our therapy, you know when you think about
19:24
one course of treatment for a patient is probably less than
19:28
$10,000, which is an order of magnitude or more lower than
19:32
auto car T And from a development standpoint, we don't
19:36
even have to outsource that. We can actually do it ourselves
19:39
in a very modest facility, which you had a chance to see when you
19:43
were in San Diego, 9000 square feet that at capacity could
19:47
treat 500 patients. So you have here a therapy that
19:51
is very scalable. It can be manufactured at a low
19:54
cost. And now we get into the clinical
19:57
advantages. So if you can drive the same
19:59
level of efficacy without the side effects that auto part T
20:04
brings, that means that you could actually give this drug IV
20:07
in a community setting. So our trials in autoimmunity
20:11
have been run. In community settings, I'm not
20:14
talking about, you know, the outpatient infusion center of an
20:18
academic center. I'm talking about a community
20:21
rheumatology practice where the rheumatologist treats his or her
20:26
patient in his or her infusion chair and then the patient goes
20:30
home. The way they administer typical
20:32
biologics. We have no CRS, we have no
20:35
Icans. So you don't need that level of
20:38
monitoring that is required of a lot of these other T cell
20:41
approaches. And we try to move really
20:44
quickly playing to the strengths that I just mentioned to you
20:49
into some of the larger autoimmune indications.
20:51
So we announced that our lead indication is refractory RA.
20:56
Why? Because you know, our drug is
20:59
effective enough based on the efficacy that we have
21:02
demonstrated. It is safe enough to be given in
21:04
the community setting. It's scalable enough such that
21:08
if you're addressing a really large indication like refractory
21:11
RA, you can actually make enough drug product without it being a
21:16
constraint. And because it's a big area of
21:18
unmet need, there's a lot of drugs that have been approved in
21:22
RA, but most of their drugs have been tested in a first line
21:26
setting or a second line setting.
21:28
And if you do have RA and you have to take your first
21:31
biologic, there's a lot of options to choose from.
21:34
We even have the option of a Jack one in the form of an oral
21:37
pill. But after you fail 2 distinct
21:40
classes of drugs, now your opportunity to have a good
21:44
response is really low. And we just share data at the
21:48
last few large just a few months ago, demonstrating that we can
21:52
drive a high degree of response rates.
21:55
We had an ACR 50 in the 71% and that these responses can
22:01
actually be quite durable. So our target product profile is
22:05
a cell therapy that drives a high rate of response.
22:11
While you are in response, you don't have to take other
22:14
immunomodulatory drugs which end up compromising your immune
22:17
system. And then because it's an off the
22:19
shelf therapy and you can redose, you can get a bit again
22:23
121824 months later. And when you do, we're hoping to
22:28
demonstrate that like, again, you can drive a deep level of
22:31
response that is durable and then you can start to
22:34
contemplate a therapy that could potentially keep a patient in
22:39
response for years with very infrequent infusions.
22:43
And in between those infrequent infusions, you're off of your
22:47
other immunomodulatory drugs. So we really think that this is
22:50
a paradigm shift for how patients with refractory RA are
22:55
treated because no drug has ever been approved for refractory RA.
23:01
And we would be the first out of all the DB cell depleting
23:06
products and modalities to get to market for refractory RA if
23:11
we are successful since we were the first one to actually
23:15
initiate a phase three trial in refractory RA, which we are
23:19
starting right now as we speak. It's so exciting.
23:24
I, I can feel the enthusiasm from you as well, which is just
23:28
awesome. You said you're starting the the
23:31
phase three and just talk us through milestones next 12 to 24
23:37
months that we should be looking out for on top of that.
23:41
So the the phase three trial will likely read out.
23:44
We have guided that we would like to read out in the
23:48
second-half of 2028, right. So we are a couple years away
23:53
from having registrational data on a product that could go into
23:57
refractory RA, right. So that's really exciting.
24:00
But that is a randomized control trial.
24:02
So we won't be getting a lot of news from that trial for a
24:06
couple of years. In parallel though, we are
24:09
running our basket study and this basket study includes RA as
24:14
well as a few other indications which I'll talk about in RA.
24:18
The value of this basket study, the value of this open label
24:21
study that we're running is that whereas we share data on roughly
24:26
21 RA patients, we're going to be enrolling over 50 RA
24:30
patients. That will give us a lot of
24:32
confidence around the primary endpoint that we're using in the
24:37
randomized control trial. And we will continue to update
24:41
the community, you know, during ulars and Acrs as to how that
24:45
data is doing such that we're raising the awareness of the
24:48
product. We're getting practitioners to
24:51
understand the potential of our therapy.
24:53
And then by the time the phase three reads out, then the
24:57
investment community, the medical community, they will be
25:00
very aware of the potential of the product in rheumatoid
25:02
arthritis. In rheumatoid arthritis, also
25:06
the data that we're generating is going to be increasing our
25:09
confidence level that number one, response rates remain high
25:13
#2 that this notion of not having to retreat until 12/18/20
25:19
four months is true. And then data showing that when
25:22
you retreat somebody that had a response before, then again, you
25:26
can drive them into a response. So that's a rich data set that
25:30
we don't have yet that will be generated in parallel to the
25:34
randomized control trial and that'll kind of complete the
25:37
foundational data set that we need for people to be excited
25:40
about this and its potential launch.
25:43
Now in parallel to RA, our basket study also includes
25:49
Sjogren's patients, myositis and Scleroderma.
25:53
So these are three additional indications that with diseases
25:57
that are treated by the same practitioners that actually
26:00
treat RA, where we are beginning to demonstrate the efficacy of
26:04
our product. In fact, that ular when we share
26:07
data on 21 RA patients, we also share data on 11 Sjogren's
26:12
patients and on five Scleroderma patients, trying to make the
26:16
case that we are seeing efficacy in all the indications that we
26:21
are treating, right. So we had seen it in oncology
26:24
that was actually quite compelling and differentiated
26:27
from our peers. That's what gave us confidence
26:29
that it would also work in autoimmunity.
26:31
And now in autoimmunity, we're seeing efficacy across different
26:35
indications. So that data, again, we will
26:38
continue to share during ACRS and ulars over the next several
26:42
years to build momentum because what we want to show is that
26:46
this is a highly efficacious drug safe enough to be used in
26:50
the community and that one can use it for a, you know, for
26:54
multiple refractory indications. That's the hope.
26:58
Yeah, it's exciting. I can't wait to see it for sure.
27:01
Thanks so much for coming on and explaining it as well.
27:03
Fred, we've got one final question, which is the the usual
27:08
final question for for each guest.
27:12
If you could have dinner with any scientist or innovator, past
27:15
or present, who would it be and why you know?
27:18
My choice is actually Elon Musk. I don't know if you have read,
27:24
you know, his biography by Walter Isaacson.
27:27
I have, yeah. That really impressed me about
27:30
him. You know, put all the politics
27:33
aside and his involvement in politics, which I'm not sure
27:36
he's feeling excited that he ever got involved with that to
27:39
begin with. You know, here's someone who
27:43
just seems relentless at trying to solve problems at the
27:48
frontier of technology, right? Like, you know of a lot of
27:52
people that they run a company and then that company's
27:55
successful and then they're happy to go on boards and
27:58
they're happy to sort of wind down.
28:00
Here's somebody that the more success he has, he continues to
28:04
come up with new areas to invest his time and money in.
28:09
And all areas that I think we would all argue these are
28:11
important areas where breakthroughs in these areas
28:15
could actually impact us. So as much as I have always
28:18
considered myself to be a very driven person, you know, just
28:23
reading about him and seeing all the things he does, I really do,
28:28
you know, wonder where that inspiration and that tenacity to
28:32
keep plowing ahead comes from. Yeah, I agree.
28:38
Yeah, I think I find so many things interesting about him.
28:41
One of the main things, he'll come up with an idea and he'll
28:46
roll with it and then he'll think about how he makes it an
28:48
actual profitable business down the line.
28:51
You know, you take SpaceX, for example, The I, I just think
28:54
he's, his mindset is like no other.
28:57
But thank you so much for coming on, Fred.
29:00
It's been an absolute pleasure. And yeah, we'll definitely talk
29:05
soon. Thank you, Max, it was nice
29:07
speaking with you. And please everyone like and
29:10
subscribe to the Bio Hub and and thanks again, Fred.