Latest / Vanguards of Healthcare by Bloomberg Intelligence / John Maraganore Reflects on the Long Game of RNAi and Drug Innovation

Transcript

John Maraganore Reflects on the Long Game of RNAi and Drug Innovation · Vanguards of Healthcare by Bloomberg Intelligence

0:24
Speaker 1: Welcome to another episode of Vanguards of Healthcare, Bloomberg Intelligences
0:28
Speaker 1: healthcare podcast where we talk to leaders in their life
0:32
Speaker 1: sciences industry, including biotech leaders and pharmaceutical leaders. Bloomberg Intelligence
0:37
Speaker 1: is a research platform for Bloomberg with over five hundred
0:41
Speaker 1: analysts and editors. Today, I have the pleasure of hosting
0:46
Speaker 1: John Marganore, who now I think is fair to say
0:50
Speaker 1: John that is leading a portfolio approach with some companies
0:55
Speaker 1: being perhaps more involved in than others, et cetera. But
0:58
Speaker 1: obviously he has a very long history in the biotech
1:01
Speaker 1: sector and as a founder and chief executive of Anylum
1:05
Speaker 1: for almost two days, just over two decades, I think. So.
1:09
Speaker 1: My name is Sam Frazelli, of course, and I'm one
1:11
Speaker 1: of the senior farmaists at Bloomberg Intelligence, and so I
1:15
Speaker 1: have the pleasure of having this podcast today and I
1:18
Speaker 1: think we can learn a lot from John. Welcome John,
1:21
Speaker 1: Thank you Sam.
1:21
Speaker 2: It's great, it's great to be here and great to
1:24
Speaker 2: spend some time with you early in the year.
1:26
Speaker 1: It is early in the year. Unfortunately I didn't make
1:29
Speaker 1: it to JP Morgan, but I've already booked my hotel
1:31
Speaker 1: for next year. Let's hope that I can make it
1:33
Speaker 1: work this time and we can enjoy each other's company
1:38
Speaker 1: at the biotech hangout drinks that we do when we're
1:41
Speaker 1: over there.
1:42
Speaker 2: Hopefully the weather is as good as it was this year.
1:45
Speaker 1: Well, remember I come from England, so I'm not sure
1:49
Speaker 1: I can guarantee that, right.
1:51
Speaker 2: Yeah, it's fine, John.
1:53
Speaker 1: Your history I've looked at and you know what, the
1:56
Speaker 1: people who listen to this podcast are very interested in
1:59
Speaker 1: hearing about what experts and operating specialists think about the
2:05
Speaker 1: current state of biotech, et cetera, et cetera. But I
2:08
Speaker 1: think the lessons learned on a two decade journey in
2:11
Speaker 1: a biotech company are also invaluable because a lot of
2:15
Speaker 1: folks who are interested in investing in biotech are younger
2:20
Speaker 1: than certainly me and possibly you, and therefore don't have
2:24
Speaker 1: the same experience. So we're going to talk about some
2:26
Speaker 1: of the lessons that were learned during that period. But
2:28
Speaker 1: did you want to just give us a quick rundown
2:32
Speaker 1: on your life and time up to your PhD From
2:35
Speaker 1: your PhD in nineteen eighty six, the companies you were
2:38
Speaker 1: involved in before al Nilam and what triggered the idea
2:41
Speaker 1: for al Nylum.
2:42
Speaker 2: Yeah, no, thanks Sam. I mean, look, I've now just
2:46
Speaker 2: surpassed forty years of time in the biotech industry, which
2:52
Speaker 2: I guess is a long time, almost a lifetime, I guess,
2:55
Speaker 2: but really quite an amazing journey. I got my PhD
2:59
Speaker 2: at either Or Chicago in nineteen eighty six. Then I
3:02
Speaker 2: went to do a post hocket at the Upjohn Company,
3:06
Speaker 2: which is in Kalamzuo, Michigan and now part Offizer. After
3:13
Speaker 2: doing that, I went to a company called Zimagenetics, which
3:17
Speaker 2: is in Seattle, and spent only a year there. But
3:20
Speaker 2: that was a company that ultimately got acquired by Bristol
3:22
Speaker 2: Myers for you know, one of their programs, but what
3:25
Speaker 2: had been previously acquired by Nova Nordisks. So rare interesting
3:30
Speaker 2: example of a company that was bought by one company,
3:34
Speaker 2: spun out separately again, and then bought by another company
3:38
Speaker 2: to end its life cycle. I wasn't there for any
3:40
Speaker 2: of that stuff. I was just there for a year
3:42
Speaker 2: as a scientist, and then I joined Bigen in the
3:46
Speaker 2: late eighties and spent a decade at Bigen helping the
3:50
Speaker 2: company transition from research into commercial. Ultimately I went to
3:55
Speaker 2: Millennium did a six year stint at Millennium between ninety
3:59
Speaker 2: seven and in two thousand and two and was part
4:02
Speaker 2: of the senior team building you know that that very
4:04
Speaker 2: famous genomics company now part of Takeda. And then in
4:08
Speaker 2: two thousand and two, I left Millennium to go to
4:12
Speaker 2: be the founding CEO of al Nylum and alum had
4:16
Speaker 2: already been had been funded, it was already started by
4:20
Speaker 2: you know, venture capitalists, but it was really just at
4:23
Speaker 2: the beginning stage. Well, it was completely at the beginning
4:27
Speaker 2: of his journey and joining al Nylam leading it for
4:30
Speaker 2: twenty years, you know, helping make helping be part of
4:32
Speaker 2: a team that made Arnie I Therapeutics reality was by
4:35
Speaker 2: far my most amazing experience and joy professional joy in
4:40
Speaker 2: my life and really a fantastic journey. And since you know,
4:44
Speaker 2: the beginning of twenty two, I've been taking a different
4:47
Speaker 2: approach in my in my life working with a large
4:51
Speaker 2: number of venture groups companies as a board member and
4:55
Speaker 2: founder from time to time, and then advisor to a
4:59
Speaker 2: larger number of CEOs. But it's it's an opportunity to
5:03
Speaker 2: really be a multiplier, as I like to say, in
5:06
Speaker 2: the industry, not just work for one company one thing
5:09
Speaker 2: but to be probably dispersed across a broader array of
5:13
Speaker 2: opportunities and leadership.
5:16
Speaker 1: Yeah, so I wanted to two thousand and two when
5:19
Speaker 1: the company was formed. I don't remember where SI RNA
5:23
Speaker 1: was at the time. I think it was a scientific traduy, right.
5:26
Speaker 1: I remember sitting at was it a coffee or breakfast
5:31
Speaker 1: with I think it was Michelle Bess was that atlas?
5:35
Speaker 1: I forgot the right the right area all those years
5:38
Speaker 1: ago and ask me. He said to me, what do
5:40
Speaker 1: you think of RNAi? I said, what? So it was
5:44
Speaker 1: it was in the very early days. So of course
5:46
Speaker 1: that kind of didn't make me did there wasn't enamored
5:49
Speaker 1: with my response At the time. I was just a
5:53
Speaker 1: newly minted I guess two thousand and one, two thousand
5:56
Speaker 1: and two biotech analyst hadn't been in the sector for
5:59
Speaker 1: about three years. So that's my excuse anyway. And of course,
6:04
Speaker 1: look where we are now, and I think quite a
6:05
Speaker 1: lot of your projects are in the RNAA space now.
6:08
Speaker 1: And look how many drugs I mean I counted one, two,
6:10
Speaker 1: three for five at eight out of anylum eight.
6:15
Speaker 2: Well out of six six there are six out of
6:18
Speaker 2: all nylum and then there are two additional medicines that
6:22
Speaker 2: have reached the market, one from Arrowhead and the other
6:25
Speaker 2: from Dicerna slash Nova Nordisk. But eight, and you know,
6:30
Speaker 2: I mean there's there are RNI programs that are in
6:34
Speaker 2: registration or soon to be in registration, like some DSRAND
6:38
Speaker 2: for my CNI gravis from Regeneron. But there are hundreds
6:43
Speaker 2: of programs in the clinic right now. So you know, sam,
6:46
Speaker 2: I I dare to say, I suspect that RNAi based
6:51
Speaker 2: medicines will approach, rival, maybe exceed what we've seen with
6:57
Speaker 2: monoclonal antibodies historically, with over twenty drugs that have been
7:01
Speaker 2: approved since the mid nineties when the first product was approved.
7:06
Speaker 2: So it's completely conceivable that this category of medicines you know,
7:14
Speaker 2: continues to deliver you know, high impact for patients and
7:18
Speaker 2: important medicines for the industry. And it's super excited, exciting
7:23
Speaker 2: to see all that because to your point, when we
7:26
Speaker 2: started at El Nilam in two thousand and two, when
7:28
Speaker 2: I started the company was only you know a few
7:31
Speaker 2: months old, and you know, the seminal work by Firomelo
7:35
Speaker 2: had been published in nineteen ninety eight, and the work
7:38
Speaker 2: that showed that small interfering RNAs mediate RNAi was done
7:43
Speaker 2: by the Almylem founders, led by Tom Tushel and Phil Zaymoor.
7:48
Speaker 2: So really very early days when we got started, very
7:52
Speaker 2: much a science experiment, and it took incredible toil and
7:57
Speaker 2: perseverance and effort to ultimately make this work. Our first
8:02
Speaker 2: drug didn't reach the market for sixteen years after we
8:05
Speaker 2: got started. So it it gives you a sense of
8:08
Speaker 2: how long it takes to you know, bring this type
8:11
Speaker 2: of innovation to patients.
8:12
Speaker 1: Yeah, I just I just wonder sometimes whether folks these
8:15
Speaker 1: days have the patients for that. But let's get back
8:17
Speaker 1: to that. So this was cool, This was quite an
8:20
Speaker 1: interesting I mean, these must have been the days where
8:24
Speaker 1: in two thousand and two the science was was still science.
8:27
Speaker 1: I mean I don't know when when you started the
8:29
Speaker 1: company or when the company started, it was still animal studies,
8:34
Speaker 1: no human exposure.
8:35
Speaker 2: Right, that's right, Oh my god, not even not even
8:40
Speaker 2: animal studies, Sam, Well, you started the company. There were
8:43
Speaker 2: cell experiments, how about that. But we had to go
8:47
Speaker 2: from the sell to you know, furry animals, to you know,
8:53
Speaker 2: slightly bigger furry animals, to ultimately humans, and it was
8:57
Speaker 2: a journey. I mean, the first program that we brought
9:00
Speaker 2: into the clinic, which never made it as a product,
9:04
Speaker 2: was targeting respiratorist and soitual virus with an aerosolized delivery,
9:09
Speaker 2: and that started clinical testing in late two thousand and five,
9:13
Speaker 2: so you know, about about three years after we got started,
9:16
Speaker 2: which you know, that's par for the course, I would say,
9:19
Speaker 2: in terms of timelines to get you know, drugs into
9:22
Speaker 2: the clinic for a new co But of course that
9:25
Speaker 2: product never made it. It was never successful, never never
9:28
Speaker 2: completed clinical testing. We didn't really know what we were doing,
9:31
Speaker 2: I have to say with that, with that program to
9:34
Speaker 2: some extent, I mean we thought we did, but but.
9:37
Speaker 1: You were testing testing a lot of different things there.
9:39
Speaker 1: That delivery getting across the mucus sufficient, I don't know
9:46
Speaker 1: a number amount of oign a versus virus getting into
9:49
Speaker 1: the deeplung All those things were added here. Of course,
9:52
Speaker 1: I'm wondering whether part of the issue was that you
9:54
Speaker 1: didn't particularly want to start with a with an injector
9:57
Speaker 1: with an IV into a human.
9:59
Speaker 2: Well, that's it, that's actually completely correct. I mean, our
10:02
Speaker 2: initial strategy, our foundational strategy, was to use direct delivery
10:06
Speaker 2: to tissues and organs, whether it's aerosolized or intravitrial, but
10:13
Speaker 2: localized delivery I would say, versus systemic delivery, because we
10:17
Speaker 2: didn't know how to achieve systemic delivery. Not until not
10:21
Speaker 2: until about the turn of the decade in twenty around
10:26
Speaker 2: twenty ten, did we finally figure out how to efficiently
10:31
Speaker 2: deliver ARNII therapeutics systemically and in particular to deliver But
10:37
Speaker 2: it took us. It took us time to get there.
10:40
Speaker 1: It's a new technology. So now when I look at
10:42
Speaker 1: the history IPO was in two thousand and four, it
10:46
Speaker 1: was these days we had in the nineteens and twenties
10:52
Speaker 1: huge as we all know Russia of IPOs. Many of
10:56
Speaker 1: the witch where you could say had the same sort
11:00
Speaker 1: of characteristics recently formed companies with an idea that I
11:04
Speaker 1: was still in pre clinical And I mean you kind
11:07
Speaker 1: of raised the number now that most people will laugh
11:09
Speaker 1: at the thirty million dollars net at the time of
11:13
Speaker 1: the IPO, that's right, And it was right after the
11:16
Speaker 1: the other nuclear winter, which came on the back of
11:20
Speaker 1: the dot com at first. So talk to me about
11:23
Speaker 1: you know a lot of people go, oh, we don't
11:25
Speaker 1: want any of these companies anymore. We want companies with
11:27
Speaker 1: proven at least phase one, phase two data, et cetera.
11:32
Speaker 1: And yet here's one that did work. Of course, you know,
11:35
Speaker 1: many fail, but we do. We want to make a
11:40
Speaker 1: decision about the IPO window never being allowing high science,
11:46
Speaker 1: low proof. Still, in terms of human data companies through
11:50
Speaker 1: at that early stage, is that something that we should
11:53
Speaker 1: avoid or is your God telling you just let the
11:56
Speaker 1: market decide and let it go.
11:58
Speaker 2: Well, I think you have to let the market decide.
12:00
Speaker 2: I'm not sure what the authority or who the authority
12:02
Speaker 2: or what the authority would be to say thou shalt
12:05
Speaker 2: not go public, thou shalt be able to go public.
12:09
Speaker 2: I mean, I guess some there are some rules in
12:12
Speaker 2: some exchanges, as you know globally, where there are limitations
12:15
Speaker 2: to you know, what type of company can go, Do
12:17
Speaker 2: they have revenues, are they profitable? And this and that
12:20
Speaker 2: the other. So yeah, we could institute those type of rules,
12:23
Speaker 2: I guess as a matter of policy and law. But
12:27
Speaker 2: I don't think that's the right thing. I think we
12:29
Speaker 2: should always let the market dictate, you know, when something
12:32
Speaker 2: like that happens. At least I from one believe in
12:35
Speaker 2: a market based approach. So I would say the following,
12:39
Speaker 2: which is, when we went public in two thousand and four,
12:42
Speaker 2: we felt that we could be successful as a public company.
12:46
Speaker 2: We felt that we would have newsflow as a public company.
12:49
Speaker 2: We thought that we would you know, be able to
12:52
Speaker 2: bring products to the clinic, which we did, and you know,
12:55
Speaker 2: we rewarded our IPO investors. It was a difficult IPO,
13:00
Speaker 2: we rewarded them with you know, well over one thousand
13:04
Speaker 2: percent return if they stuck with the stock over time.
13:07
Speaker 2: So you know, I'm not sure that we did a
13:09
Speaker 2: bad thing for those investors that they stuck with the story,
13:12
Speaker 2: and frankly we didn't. We really traded relatively well, you know,
13:17
Speaker 2: during the course of our public company life. I mean, yes,
13:20
Speaker 2: there were times in which we you know, had dips
13:22
Speaker 2: in our in our story, but you know, we always
13:26
Speaker 2: traded I think reasonably well as a stock and rewarded
13:29
Speaker 2: those IPO investors quite well.
13:31
Speaker 1: Right. So two thousand four IPO thirty million dollars net,
13:34
Speaker 1: two more raises in two thousand and six January about
13:38
Speaker 1: sixty eight million, seventy million, and in December one hundred
13:40
Speaker 1: and seventy million. Then nothing between two thousand and six
13:45
Speaker 1: and twenty eleven. If you've got my data right, that's
13:49
Speaker 1: not right. What how did you survive? And I mean
13:53
Speaker 1: I'm sure you did deals et cetera.
13:55
Speaker 2: Right, farmer deals, farm me deals of somewhat epic proportion
13:59
Speaker 2: at the time, I would say, I mean, look, I mean,
14:01
Speaker 2: I forget all the details, Sam, But in aggregate, during
14:05
Speaker 2: my time at Alalam, we raised over seven point five
14:08
Speaker 2: billion dollars of capital. Half of that, literally half of that,
14:12
Speaker 2: just over three billion, came from pharmaceutical company alliances.
14:16
Speaker 1: That we formed what we would call non dilutive.
14:18
Speaker 2: Non well you know there's some is yeah, yeah, yeah,
14:23
Speaker 2: totally non diluted. But I would say, I would say,
14:26
Speaker 2: relatively from an equity standpoint, nondoluted capital. You know, yes,
14:30
Speaker 2: we gave product rights away or or a partner in
14:33
Speaker 2: our product rights, so there was a form of dilution there,
14:35
Speaker 2: but but a remarkable, you know, amount of capital that
14:39
Speaker 2: we raised and relatively little from the equity markets. At
14:43
Speaker 2: the end of the day, Why did.
14:45
Speaker 1: You do that? Of course, five six, seven went bad years.
14:49
Speaker 1: There weren't difficult.
14:50
Speaker 2: Times, yeah, yeah, yeah, But but they were also years
14:54
Speaker 2: in which there was still quite a bit of enthusiasm
14:58
Speaker 2: for the rn EI approach, and we were able to
15:02
Speaker 2: capitalize on that enthusiasm with very large pharmaceutical deals. For example,
15:07
Speaker 2: in two thousand and seven, we did a deal with
15:11
Speaker 2: Roche for three hundred and thirty million dollars up front
15:15
Speaker 2: to basically give them access to our technology platform. They
15:20
Speaker 2: ended up dabbling with it for a grand total of
15:22
Speaker 2: three years, hardly a yeoman's try, I would say, and
15:26
Speaker 2: then ended up exiting their RNAi investment in twenty tens
15:31
Speaker 2: as they ran into P and L pressures and had
15:33
Speaker 2: to make prioritization decisions post their acquisition at Genentech. So
15:38
Speaker 2: that turned out to be incredibly good capital for us
15:41
Speaker 2: because they never did anything with any product. Then it
15:46
Speaker 2: handed us three hundred and thirty one million dollars and
15:48
Speaker 2: the rights back, all the IP that was everything, everything back,
15:53
Speaker 2: absolutely And.
15:54
Speaker 1: They must have spent some money on it themselves, right.
15:56
Speaker 2: Oh they did, they did, of course, they spent some
15:59
Speaker 2: money out but we love you know, they never gave
16:00
Speaker 2: it a serious They never give it a serious try,
16:02
Speaker 2: and ended up being obviously a source of capital for us.
16:06
Speaker 1: Actually, let me digress there for a second. How many
16:09
Speaker 1: farmer deals do you think belong in this bucket? I mean,
16:12
Speaker 1: so we haven't done the scientific analysis, but and I
16:14
Speaker 1: don't know how you would do it, but.
16:16
Speaker 2: Just a gut the industry, across the industry, I would
16:20
Speaker 2: say that the vast majority of deals turn out to reward,
16:25
Speaker 2: you know, be associated with capital transfer from the pharma
16:28
Speaker 2: to the biotech without any fruit coming out of it
16:33
Speaker 2: for the pharmer company. Not you know, let's say sixty
16:37
Speaker 2: seventy percent. As high as that, i'd be worth doing
16:42
Speaker 2: an analysis across the industry historically.
16:44
Speaker 1: I don't know how you do it. I mean I do,
16:46
Speaker 1: but it's going to take time because you have to
16:47
Speaker 1: go back to every single thing and see what actually
16:50
Speaker 1: came out of it. Now did Maybe? Maybe that's something
16:53
Speaker 1: that I'll put on my list of very large list
16:56
Speaker 1: of things to do. But that's a good enough like.
16:59
Speaker 2: A spare minute the minute.
17:01
Speaker 1: Yeah yeah, yeah, Now we got we're European, we go
17:04
Speaker 1: on holiday in August. You've lost your European.
17:06
Speaker 2: Cyberget Yeah, I forget, I forget.
17:09
Speaker 1: Yeah. No, So that's that's that's interesting. Of course, if
17:13
Speaker 1: you got access to that sort of money, why would
17:14
Speaker 1: you And also you know, with the possibility that you're
17:18
Speaker 1: going to get a lot more out of that relationship.
17:20
Speaker 1: The cash is there, you get something out of it,
17:22
Speaker 1: either a product out of it or development of the
17:24
Speaker 1: of the or what exactly happened? So and then of
17:27
Speaker 1: course the stock price was I mean it had been
17:31
Speaker 1: up and down six dollars was the IPO price, it
17:33
Speaker 1: had been up to about thirty or forty at what
17:36
Speaker 1: point during that period before it really got motoring in
17:39
Speaker 1: twenty thirteen or so? And was that a challenge in
17:43
Speaker 1: terms of keeping investors close? In terms of employees, you know,
17:48
Speaker 1: options matter to a lot of people, especially in a
17:51
Speaker 1: fast growing sector where others are interested in your in
17:54
Speaker 1: your well trained biologists and people. So what what what
17:59
Speaker 1: did you learn there? What advice do you have for
18:01
Speaker 1: companies now that go through inevitable periods of difficulty with
18:04
Speaker 1: regards to at least their share price.
18:07
Speaker 2: Yeah, I mean, look, I think I think that you know,
18:10
Speaker 2: for the investors, what was important was to see the progress,
18:16
Speaker 2: whether it was in the deals that we made or
18:18
Speaker 2: the clinical or pre clinical you know, clinical data ultimately
18:22
Speaker 2: that that mattered. They just needed to see those those
18:27
Speaker 2: those those data points over time, and there were some
18:30
Speaker 2: investors during that journey that were in and out of
18:32
Speaker 2: the stock on probably several occasions. And there were others
18:36
Speaker 2: who were longtime holders of the stock who stuck with it,
18:39
Speaker 2: believed in the science, believed in the team, believed in
18:43
Speaker 2: us to make this happen. So I think that, you know,
18:48
Speaker 2: when you think about that long journey before the real inflection,
18:52
Speaker 2: which started, as you said, around twenty thirteen, you know,
18:55
Speaker 2: there were ups and downs in there, but people saw
18:57
Speaker 2: data that data could be business results or or you know,
19:03
Speaker 2: science results that ultimately kept them involved and excited about
19:07
Speaker 2: the potential of RNAi. You know, people saw that if
19:10
Speaker 2: we figured this out, it could be huge and and
19:13
Speaker 2: you know, those people that bought into that thesis and
19:15
Speaker 2: stuck with the stock got rewarded enormously on employees, you know. There,
19:21
Speaker 2: I got to tell you what was remarkable about al Mileam,
19:24
Speaker 2: and I think for many companies that have a similar
19:27
Speaker 2: scope of potential impact, is you develop a real sense
19:33
Speaker 2: of purpose within the organization around you know, figuring something out,
19:38
Speaker 2: you know, being the being the group that would figure
19:41
Speaker 2: out how to make drugs out of small interfering RNA
19:44
Speaker 2: and so, and then ultimately the connection to patients, and
19:48
Speaker 2: so you create a remarkable cohesion around a purpose, a mission.
19:56
Speaker 2: It was the mission, if you will, of making RNI
20:00
Speaker 2: reality that kept the employees together much more than you know,
20:05
Speaker 2: the stock price on any given day. I mean, our
20:08
Speaker 2: our scientists were you know, driven by the potential to
20:13
Speaker 2: do something big in their life and for you know,
20:15
Speaker 2: for patients and and and society more than you know,
20:20
Speaker 2: the ups and downs of the stock market, if you will,
20:23
Speaker 2: you know, I mean, they're they're driven by you know, excellence. Now,
20:27
Speaker 2: one thing we did was was we had a very
20:30
Speaker 2: open approach on publishing, and so our scientists published papers
20:34
Speaker 2: and Nature and Sell and you know, Science and all
20:40
Speaker 2: different journals, presented at scientific meetings. And so they were
20:44
Speaker 2: motivated around the scientific mission of the company in in
20:48
Speaker 2: a way that I think was extremely strong and cohesive
20:51
Speaker 2: to keep the company aligned and on this mission.
20:54
Speaker 1: Yeah. So that's interesting because it took a while, right
20:58
Speaker 1: if I look at this, Yeah, I think said that
21:00
Speaker 1: eighteen years from founding, you know, to get the first
21:04
Speaker 1: drug approved Steen years, sixteen years as a yes, yes,
21:09
Speaker 1: eighteen takeaway, Yeah, that's right, So of course it's right.
21:12
Speaker 1: And then a slew of approvals pretty much one a
21:14
Speaker 1: year and even two in one year. How did it?
21:16
Speaker 1: I mean, I guess that was the fruit of being
21:19
Speaker 1: able to run a pipeline, because a lot of biotech
21:23
Speaker 1: companies tend to I mean, you had the technology platform.
21:26
Speaker 1: So that's an interesting conversation to have too, because the
21:29
Speaker 1: VC community, they investor community, they get hot and cold
21:32
Speaker 1: with regards to do they want an asset based company
21:35
Speaker 1: or do they want a technology based company? And you
21:38
Speaker 1: definitely were in the technology based camp, and I think
21:41
Speaker 1: the model shows that this particular approach then led to
21:45
Speaker 1: lots of fruits. How much can I take that? As
21:49
Speaker 1: so hard to because it was could be quite specific
21:52
Speaker 1: because you were at the beginning of a of a
21:54
Speaker 1: technology that hadn't been particularly brought into by everybody. There
21:59
Speaker 1: was only two or three two companies that I would
22:01
Speaker 1: say that were obvious, Ionis and Alilum. What should I
22:06
Speaker 1: learn from that as I think about my next investments
22:09
Speaker 1: in biotech?
22:10
Speaker 2: Yeah? Well, I mean, I think the thesis behind el
22:13
Speaker 2: Nylum from the beginning was that if we conquer, if
22:16
Speaker 2: we figure out how to deliver ourni therapeutics, we could
22:19
Speaker 2: have a whole new class of medicines and therefore a
22:21
Speaker 2: pipeline of high impact medicines and products and generate this
22:25
Speaker 2: staccato ultimately of approvals that we that we that we
22:30
Speaker 2: demonstrated in twenty eighteen, nineteen, twenty twenty one and so forth.
22:33
Speaker 2: As you say, virtually one approval every year of important medicines. Now,
22:38
Speaker 2: you know, it takes a board and investors aligned around
22:43
Speaker 2: that opportunity set to make it work. It also takes
22:48
Speaker 2: management that can you know, execute well and bring the
22:53
Speaker 2: balance sheet to the point where you're not forced by
22:56
Speaker 2: circumstances to basically focus down on one product. I mean,
23:00
Speaker 2: I think often what happens, and I've seen this when
23:04
Speaker 2: you have a technology based company, platform based company with
23:09
Speaker 2: the potential for you know, many approvals, many many opportunities,
23:14
Speaker 2: they ultimately get forced down to do one thing when
23:17
Speaker 2: the balance sheet gets to the point where they have
23:19
Speaker 2: no choice and they almost have to put their platform
23:22
Speaker 2: on the shelf and let it, let it be till
23:25
Speaker 2: they can live another day. I think we just were
23:29
Speaker 2: able to do these pharmaceutical deals. I mean, Sam, even
23:32
Speaker 2: when we were in our darkens of winters in twenty ten,
23:37
Speaker 2: twenty eleven, we were trading under cash. We had a
23:40
Speaker 2: balance sheet of over three hundred million dollars at that
23:43
Speaker 2: time because we did all these pharmaceutical deals in the
23:47
Speaker 2: first half of our of that decade, and so we
23:51
Speaker 2: were able to you know, weather the storm and stay
23:57
Speaker 2: in a multi product oriented approach for delivering on the
24:01
Speaker 2: promise of RNAi. And so I think it really does
24:05
Speaker 2: come down to where's your balance sheet at the end.
24:08
Speaker 2: How successful have you been in raising either equity dollars
24:11
Speaker 2: from investors or or you know, doing deals that allows
24:15
Speaker 2: you to have the right to be a multi product company.
24:18
Speaker 2: And in other cases companies don't do that or they
24:21
Speaker 2: can't do that for some reason, then they're forced to
24:24
Speaker 2: make a choice. And you know, that's that's something we
24:27
Speaker 2: didn't have to do.
24:28
Speaker 1: Yeah, I mean there are kind of current stories or
24:32
Speaker 1: companies that I would that come to my mind. Now
24:34
Speaker 1: I haven't got to list it down here, but as
24:36
Speaker 1: you were speaking, think about moderna with a platform that's
24:41
Speaker 1: that's taken a lot of years too. I mean, they
24:43
Speaker 1: were in a I don't know how you could call
24:46
Speaker 1: that fortunate unfortunate position. Yeah, we were fortunate and they
24:50
Speaker 1: were fortunate. The world was unfortunate to have a pandemic
24:52
Speaker 1: to deal with, and that really helped them to rapidly
24:55
Speaker 1: move forward, generate some revenue, get a pretty dechage balance sheet,
24:59
Speaker 1: same as Bionte, And that is a platform that might
25:03
Speaker 1: at some point, if I look another ten years down
25:05
Speaker 1: the road, lead to this or actually it's not that
25:08
Speaker 1: I don't have to wait that far. But then I
25:10
Speaker 1: think about companies like Revolution Medicine with their platform that there,
25:14
Speaker 1: I would say that they're using for RAS modulation for example.
25:18
Speaker 1: How much though, because some of the nuts that these
25:22
Speaker 1: companies are trying to crack oncology, I guess it's a
25:25
Speaker 1: little bit relatively speaking, and relatively speaking easier than as
25:30
Speaker 1: a specialty business or area than a primary care area.
25:35
Speaker 1: And we'll get to that by talking about some of
25:36
Speaker 1: the companies you're involved with now. But how much of
25:39
Speaker 1: this success and ability to deliver in the end had
25:45
Speaker 1: to do with the diseases that you picked and the
25:47
Speaker 1: types of trials that you could do, size, speed is relative,
25:53
Speaker 1: ease of recruitment, et cetera.
25:55
Speaker 2: Well, we did take we did explicitly decide to focus
25:59
Speaker 2: on rare disease. It's in part because we wanted to.
26:03
Speaker 2: We wanted to focus on disease targets that were genetically
26:06
Speaker 2: validated and oftentimes as an exus of genetic validation with
26:10
Speaker 2: monogenetic disease and rare disease. And of course that has
26:15
Speaker 2: the benefits of enabling much smaller data sets for regulatory
26:21
Speaker 2: approval number one and number two. It also has the
26:24
Speaker 2: benefit of enabling commercialization with a much more focused marketing
26:28
Speaker 2: and selling effort compared to a larger market opportunity. And
26:33
Speaker 2: we always wanted to go to market ourselves and be
26:36
Speaker 2: directly involved in commercialization of our drugs. We ultimately did
26:40
Speaker 2: it globally and directly in twenty countries around the world
26:42
Speaker 2: and distributors and just as many other countries. So the
26:47
Speaker 2: rare disease selection for us was both an R and
26:50
Speaker 2: D strategy a commercial strategy, and it turned out to
26:55
Speaker 2: be a very sound business creating strategy as well, and
26:59
Speaker 2: again alloted of us to get there with less capital,
27:02
Speaker 2: allowed us to you know, get to markets where we
27:05
Speaker 2: could be effective as a commercializer. These were all elements
27:08
Speaker 2: that were part of an explicit choice in the programs
27:12
Speaker 2: that we selected. And you know, notwithstanding the ups and
27:15
Speaker 2: downs of favor the investment community might have in rare diseases.
27:19
Speaker 2: At least during our time, people were excited about the
27:21
Speaker 2: rare disease potential. Enry Premiere showed us the way with Genzyme,
27:26
Speaker 2: and there were many other great examples out there, bio marine,
27:29
Speaker 2: ultrogenics and so forth, Amicus, many others that showed how
27:32
Speaker 2: powerful a rare disease strategy could be to bring products
27:36
Speaker 2: to patient.
27:36
Speaker 1: Yeah. I'm glad you mentioned Henry because he's one of
27:38
Speaker 1: the critical in my view, individuals in our sectors. Of course,
27:43
Speaker 1: he's not the only one, but I have friends who
27:45
Speaker 1: used to work at Genzyme and then in the different
27:49
Speaker 1: parts of the business, and you know, he has a
27:50
Speaker 1: phenomenal legacy. And I know you're involved with the Henry
27:53
Speaker 1: Semir Foundation.
27:54
Speaker 2: I think, yes, yes, yes, great.
27:57
Speaker 1: You mentioned something quite interesting now and I'm going to
28:00
Speaker 1: it's start transitioning to kind of some of the topical
28:03
Speaker 1: stuff that we discuss often amongst ourselves is scientific publications.
28:07
Speaker 1: You said that the company encouraged I'm assuming your file
28:10
Speaker 1: patterns as soon as you needed to.
28:12
Speaker 2: Yes.
28:13
Speaker 1: One of the things that I'm hearing I heard Bob
28:16
Speaker 1: Nelson on the STAT interview talking about keeping companies longer
28:19
Speaker 1: in stealth, maybe not publishing as much as a strategy
28:24
Speaker 1: to limit, for want of a better phrase, or manage
28:29
Speaker 1: the risk of helping China or any other competitor, I guess.
28:34
Speaker 1: But China specifically is what keeps bringing you coming up here,
28:37
Speaker 1: which I mean I have very strong views about this myself,
28:40
Speaker 1: but obviously that is something that those days, I suppose
28:45
Speaker 1: people didn't feel that worried, and then suddenly now we
28:49
Speaker 1: are worried because China has done what it said it
28:51
Speaker 1: would do, invest in its innovation, and life science is
28:55
Speaker 1: actually is picking up now, but they have been at
28:59
Speaker 1: the forefront of research areas outside of life sciences, way
29:04
Speaker 1: beyond what we are able to do now in terms
29:06
Speaker 1: of publications, at least in material science, chemistry, et cetera.
29:10
Speaker 1: And what is your thought on all of this? I mean,
29:14
Speaker 1: of all of this is this big topic. How worried
29:18
Speaker 1: are you as a US based individual. Remember I'm agnostic
29:22
Speaker 1: as to where these things come from. At the end
29:24
Speaker 1: of the day, I'm interested in the sector as a
29:26
Speaker 1: whole and good drugs. You know my view and our
29:29
Speaker 1: other friend Brad Lanka and I have had a couple
29:32
Speaker 1: of conversations about this. I think he has a slightly
29:34
Speaker 1: different view, although I haven't heard him recently. But what's
29:37
Speaker 1: your thought process here and should we worry? Okay, I'm
29:42
Speaker 1: going to stop there, leave you to speak. Yeah.
29:44
Speaker 2: Well, I mean i'd say this, Sam, I'm a big
29:47
Speaker 2: believer in the importance of innovation for patients and that
29:51
Speaker 2: innovation should come from anywhere in the world. I've seen
29:53
Speaker 2: it from Europe, I've seen it from US, I've seen
29:56
Speaker 2: it from you know, Japan. You know what's wrong with
29:59
Speaker 2: the coming from China? You know, other than you know,
30:02
Speaker 2: perhaps geopolitical concerns around around China US relations or China,
30:07
Speaker 2: you know, global relations. Well, guess what you know, there
30:09
Speaker 2: are concerns around US relations now with Europe, and so
30:14
Speaker 2: I think we need to be as a sector focused
30:17
Speaker 2: on innovation and wherever it comes from, it's good. It's
30:21
Speaker 2: good for patients, and that's what matters at the end
30:23
Speaker 2: of the day. I at the same time, you know,
30:26
Speaker 2: want our biotech leadership in this country, our country, the
30:31
Speaker 2: US to continue to be the best in the world. Okay,
30:34
Speaker 2: And I do think that we should approach this competitive
30:39
Speaker 2: challenge with exactly what people should do when there's competition,
30:44
Speaker 2: which is to work harder, try to figure out a
30:46
Speaker 2: way to work faster and compete fairly fairly with what's
30:52
Speaker 2: emerging from other countries in the same sector. So I
30:57
Speaker 2: believe strongly that US leadership can be maintained if we
31:02
Speaker 2: take the right steps to you know, approach the competition
31:06
Speaker 2: from China, you know, as a good competitor should do.
31:10
Speaker 2: You know, Let's lower our regulatory burdens to generate clinical
31:13
Speaker 2: evidence in clinical studies. Let's find ways to make things
31:17
Speaker 2: cheaper using artificial intelligence or robotics so that we can
31:23
Speaker 2: affect more compete more effectively on the cost side of
31:25
Speaker 2: the equation as well. These are all things that are
31:28
Speaker 2: possible for us to do and be effective competitors with
31:32
Speaker 2: what's going on in China now as far as I'm concerned.
31:36
Speaker 2: Those approaches require, at the same time, a government that
31:41
Speaker 2: will continue to invest in our research institutions, will continue
31:45
Speaker 2: to support a strong and stable and consistent FDA, will
31:49
Speaker 2: continue to reward the risk capital in our industry with
31:53
Speaker 2: market based rewards. When drugs finally get to market and
31:57
Speaker 2: we're finding ourselves in this really odd say circumstance where
32:01
Speaker 2: you know, on the one hand, policymakers in our country
32:04
Speaker 2: are worried about the threat as they call it in China,
32:07
Speaker 2: and at the same time, they're urinating on the critical
32:11
Speaker 2: elements that have made us biotech leadership so successful over
32:15
Speaker 2: the years. And you know, we'll get through this. I
32:18
Speaker 2: have no doubt. You know, our will to persevere is
32:22
Speaker 2: stronger than ever and I think that we as a
32:25
Speaker 2: sector will continue to prevail on these things. Government policies
32:29
Speaker 2: can change in the course of an election or two,
32:32
Speaker 2: and you know, I'm overall confident and I think that
32:36
Speaker 2: we actually benefit longer term from this competitive landscape that's
32:40
Speaker 2: now emerged, and ultimately patients will do better as a
32:44
Speaker 2: result of it, and that's what matters at the end
32:45
Speaker 2: of the day.
32:46
Speaker 1: Yeah, I completely agree with that in terms of the
32:49
Speaker 1: competition is what drives innovation. Yeah, and that's the thing
32:53
Speaker 1: that we're by closing the door on something. I don't
32:56
Speaker 1: think that is the way to think about it.
32:59
Speaker 2: It's the wrong way to do it, Sam and it
33:01
Speaker 2: and it has the potential of creating IP wars globally,
33:06
Speaker 2: which would just be bad for business and bad in
33:09
Speaker 2: this case for patients or other forms of commerce.
33:13
Speaker 1: So, if you wanted to have your wish list of
33:17
Speaker 1: three or four things. I mean, I think there's so
33:19
Speaker 1: many things that any administration can deliver. What would they
33:23
Speaker 1: be today? I mean, and it could be stop having
33:26
Speaker 1: a go out science and cutting the budget, et cetera.
33:29
Speaker 1: And I hear a little bit of conflicting voices on
33:33
Speaker 1: that now that that actually the NIH cuts, for instance,
33:36
Speaker 1: weren't as broad as people expected. They're not affecting everything.
33:41
Speaker 1: But let's talk about what you know is the situation
33:45
Speaker 1: right now and what areas specifically. I mean, you mentioned
33:49
Speaker 1: one reduced the regulatory burden to getting the first evidence
33:52
Speaker 1: in humans at least, and I think there's a lot
33:55
Speaker 1: of people who are speaking about that, and that is
33:57
Speaker 1: one obvious one with China in the speed with which
34:00
Speaker 1: they can go into trials and yeah.
34:03
Speaker 2: The results, yeah, and and and the good news there
34:06
Speaker 2: is that Commissioner MACKERI has has has begun now talking
34:09
Speaker 2: about this publicly, and I think he himself believes is
34:13
Speaker 2: an opportunity to lower the lower the or change the approach.
34:17
Speaker 2: Not I don't think we want to lower the ethical
34:21
Speaker 2: standards for doing human studies. I mean, you know that
34:23
Speaker 2: should never happen, but we should try to lower the
34:26
Speaker 2: bureaucratic burdens related to that, and and therefore that will
34:31
Speaker 2: have the benefit of lowering the cost and shortening the
34:34
Speaker 2: time to generate those those clinical data that are so precious,
34:38
Speaker 2: especially for early translational studies that are that are critical
34:42
Speaker 2: for innovation. So that's that's a big one. Sam. I
34:45
Speaker 2: think if we can, you know, if we can make
34:47
Speaker 2: that work, and I think I think, I think we
34:50
Speaker 2: should be able to do it. I think there's a
34:52
Speaker 2: bit of a spot Nick moment going on here in
34:54
Speaker 2: the US with regard to this point, and I think
34:56
Speaker 2: people are realizing that we have we have the means
34:59
Speaker 2: and and the and the ability. We just need the
35:02
Speaker 2: will to make this change. And you know, it shall
35:05
Speaker 2: get done at the end of the day. But that's
35:07
Speaker 2: certainly number one. I think. I think another set of them, frankly,
35:11
Speaker 2: that I feel very strongly about is I think we
35:14
Speaker 2: need to get back to you know, believing in science
35:18
Speaker 2: and believing in truth has values, and uh, these have
35:22
Speaker 2: come under attack as well. I think it's a point
35:26
Speaker 2: of grave concern because it erodes public trust in what
35:31
Speaker 2: in what science can deliver. And if we don't have
35:33
Speaker 2: public trust in what we do, we have nothing. We
35:36
Speaker 2: we nobody will care or trust the medicines that we
35:40
Speaker 2: that we develop when they should, you know, and that
35:42
Speaker 2: will have enormous harm for our broader industry. So I
35:46
Speaker 2: think that's another one that I would put high on
35:48
Speaker 2: my list, if not at the top of my list
35:50
Speaker 2: of things that you know, would be on my so
35:52
Speaker 2: called wish list if you will, of policy change.
35:55
Speaker 1: Okay, And we obviously touched on AI very recently. We
36:00
Speaker 1: did a rumored intelligence survey of C suite. I mean,
36:04
Speaker 1: it was across many industries. It was six hundred respondents
36:08
Speaker 1: that we surveyed. It took a while, as you can imagine,
36:11
Speaker 1: some interesting data points came out of it. When we
36:13
Speaker 1: specifically focused on the fifty pharmaceutical respondents, companies expecting a
36:19
Speaker 1: shift to shift about ten to twenty percent of development
36:21
Speaker 1: processes over the next five years to AI enabled systems.
36:26
Speaker 1: As many as eighty eight percent of respondents indicate that
36:29
Speaker 1: they expect the integration of a R to drive high
36:31
Speaker 1: or very high degree of disruption to the sector. Although
36:35
Speaker 1: what is the meaning of that. Of course, with any survey,
36:37
Speaker 1: you always get more questions at the end of it
36:39
Speaker 1: than anything else. Ten to thirty percent of pre clinical
36:42
Speaker 1: work may shift to AI. Over time, AI expected to
36:45
Speaker 1: reduce development times by six to eight and that this
36:48
Speaker 1: is the one that obviously has the MPV impact, putting
36:51
Speaker 1: aside mechanisms such as IRA, because what it does impact
36:55
Speaker 1: is your ability to get product to market faster, which
36:59
Speaker 1: in a normal world pattern protection will be longer than
37:03
Speaker 1: but of course in an IRA world that doesn't kind
37:05
Speaker 1: of change very much. But if you look at a
37:09
Speaker 1: normal world, six to eighteen months is a very significant
37:12
Speaker 1: amount of time in the average ten to twelve years
37:14
Speaker 1: life of a product. How do these numbers resonate with you?
37:19
Speaker 2: You know, they resonate, They resonate soundly, I would say,
37:23
Speaker 2: I mean they I was worried that the numbers you
37:25
Speaker 2: would quote would be within the hype cycle aspect of AI,
37:29
Speaker 2: which I think would be would be wrong. But I
37:32
Speaker 2: think the numbers you just said, six to eighteen months
37:34
Speaker 2: for accelerating time to market I think is completely.
37:38
Speaker 1: Over time, not tomorrow, no, no, no overtime.
37:41
Speaker 2: I think that's completely reasonable and it's reflective of the
37:47
Speaker 2: evolutionary aspect of AI on our industry, not revolutionary. I think.
37:52
Speaker 2: You know, obviously you know PCR was an evolutionary tool,
37:56
Speaker 2: and you know, sequencing genome, sequencing the whole human genome.
38:01
Speaker 2: These were all tools that have accelerated.
38:03
Speaker 1: And now we take them for granted.
38:05
Speaker 2: Activity We do take them for granted, but they I
38:08
Speaker 2: think AIS are that similar category of impact for what
38:13
Speaker 2: we do, which is amazing and and you know, deeply
38:16
Speaker 2: important for the future. But I think the numbers you
38:18
Speaker 2: quoted are all reasonable and I would I would concur
38:21
Speaker 2: with them.
38:21
Speaker 1: I think your portfolio approach now and knowledge of probably
38:26
Speaker 1: you have some knowledge std of what's happening in in
38:29
Speaker 1: aliel them, not necessarily from a board level, but generally.
38:32
Speaker 2: Yeah, yeah, I do.
38:34
Speaker 1: That gives you a unique insight into knowing what different
38:38
Speaker 1: companies are doing for leveraging AI. If you wanted to
38:42
Speaker 1: pick again just to make life simpler. Three areas where
38:45
Speaker 1: you're seeing now an application that you go, oh, that's
38:48
Speaker 1: cool that we're able to do this. I mean, I've
38:50
Speaker 1: been reading about alpha fold quite a bit and the
38:54
Speaker 1: way that it's that that it's one of those things
38:57
Speaker 1: in nature. Did they I think they quoted the study
39:00
Speaker 1: from a deep mind themselves where they looked at the
39:02
Speaker 1: number of references to the jump paper, the original twenty
39:09
Speaker 1: twenty one paper, and the curve just keeps going up,
39:12
Speaker 1: whereas in many big events, something happens and then it
39:17
Speaker 1: dissipates a bit because of the stuff takes it. So
39:20
Speaker 1: it seems like many many problems of being addressed using
39:24
Speaker 1: alpha faults. But I don't want to focus on that necessarily.
39:27
Speaker 1: I want to hear what you're seeing in terms of
39:29
Speaker 1: your companies using Now I know two of them are
39:32
Speaker 1: in RNAi space. Maybe they come into the design or something.
39:36
Speaker 1: What are you seeing if you wanted to pick like,
39:38
Speaker 1: these are the three areas where I'm seeing an impact.
39:40
Speaker 2: Now, yeah, let me give you some examples. So in
39:43
Speaker 2: I've got a couple of companies I'm deeply involved with
39:45
Speaker 2: on the discovery side. One is using AI in a
39:48
Speaker 2: small molecule discovery paradigm company called Terrae, where I have
39:55
Speaker 2: seen some pretty remarkable impact of machine learning on you know,
40:02
Speaker 2: the drug discovery process to get to lead candidates very quickly.
40:06
Speaker 2: So that's one example.
40:07
Speaker 1: Another can I just ask you to hold up. Yeah,
40:11
Speaker 1: you use the word machine learning there, I'm wondering whether
40:14
Speaker 1: you mean machine learning using the faster processes that we
40:19
Speaker 1: have today. What did you mean the l l ms
40:21
Speaker 1: that are going around now, I meant l ms okay ok.
40:27
Speaker 2: And then and then the other. The other example, which
40:29
Speaker 2: which is really cool, is a company called Villia that
40:33
Speaker 2: is using as a David Baker company and is focused
40:37
Speaker 2: on macrocycles and is using an AI based approach to
40:41
Speaker 2: you know, design macrocycle leads that can then be optimized
40:45
Speaker 2: further for drug candidates. So those are two examples on
40:49
Speaker 2: the discovery side, you know, one of my favorite examples,
40:53
Speaker 2: and you know, we'll talk about a little bit more.
40:55
Speaker 2: I'm sure of course, Sarah, which is a company I've
40:57
Speaker 2: i found in I'm actually the co CEO of this
41:00
Speaker 2: company with flag Meanwhell is focused on cardiovaster prevention. But
41:04
Speaker 2: we developed with doctor Brian Friends who's out of Cambridge
41:07
Speaker 2: in the UK, a way of predicting lifetime risk of
41:11
Speaker 2: developing cardivascer disease or heart attacker stroke which is far
41:16
Speaker 2: more powerful that it uses causal AI to basically identify
41:21
Speaker 2: people that are at risk early in their life for
41:24
Speaker 2: developing a heart attacker stroke in their sixties or seventies.
41:28
Speaker 2: And the reason that's important is that we're trying to
41:30
Speaker 2: do prevention as early as possible in people effectively begin
41:35
Speaker 2: to treat people in their thirties and forties for those
41:38
Speaker 2: that are at higher risk of developing a future heart
41:40
Speaker 2: attacker stroke, so that we can avert the cumulative exposure
41:46
Speaker 2: to things like LDL, cholesterol and blood pressure. And that's
41:50
Speaker 2: a really exciting application of AI because we wouldn't have
41:54
Speaker 2: been able to make those predictions based on previous methodologies
41:59
Speaker 2: and approaches, and so we're rather enabled by by this. Now,
42:04
Speaker 2: keep in mind the other major enabler, which we don't
42:08
Speaker 2: talk about as much, it's not hyped as much, is
42:10
Speaker 2: the availability of large data sets like the UK Buyo Bank.
42:13
Speaker 2: You know the data.
42:15
Speaker 1: Did that make a difference in Coursera?
42:17
Speaker 2: Oh huge? We couldn't have done it without it, could
42:20
Speaker 2: not have done it without it.
42:21
Speaker 1: I've heard the US is trying to get a lot
42:23
Speaker 1: of the national agencies to have their data usable in
42:27
Speaker 1: one large format. Maybe after you finish your sentence, which
42:32
Speaker 1: I keep interrupting you, you can now talk about that too,
42:35
Speaker 1: if you have any knowledge about it.
42:36
Speaker 2: Well, I mean I I let's let's just jump to
42:38
Speaker 2: it right away. I mean, I think I think you
42:40
Speaker 2: know obviously this is the This is one of the
42:42
Speaker 2: benefits of a single payer system as a national healthcare system.
42:47
Speaker 2: You know that you can see in the UK, which
42:49
Speaker 2: is that when it comes down to organizing health data,
42:52
Speaker 2: you're far more able to do it or far better
42:55
Speaker 2: equipped to do it as opposed to a very fragmented
42:57
Speaker 2: system that we have in the US. But I do
43:00
Speaker 2: I do think there are opportunities and big provider systems
43:02
Speaker 2: in the US to do this, and there's been some
43:05
Speaker 2: effort to do that, you know, with Guysenber for example.
43:07
Speaker 2: You know, there's also been efforts to do this with
43:09
Speaker 2: the Veterans Affairs set up in the US, which is
43:13
Speaker 2: obviously a very large single provider if you will, compared
43:16
Speaker 2: to the you know, otherwise fragmented healthcare system that we
43:20
Speaker 2: have here in the US. So I think there are opportunities,
43:23
Speaker 2: but you know, nothing comparis at this point to what
43:26
Speaker 2: the UK is put together with the buyoblak.
43:28
Speaker 1: That's great to hear something positive about the UK. I
43:31
Speaker 1: can tell you the biotech sector struggles here a little
43:33
Speaker 1: bit in the public in the public market, the science
43:37
Speaker 1: and the private side are ruing anyway. Yeah, well, I
43:41
Speaker 1: just wish that we were able to translate that to
43:43
Speaker 1: a thriving biotech sector. I've given up hope. I'm sorry,
43:48
Speaker 1: thriving biotech public biotech market, I've given up hope of that.
43:53
Speaker 1: I have high expectations and hopes for the science because
43:56
Speaker 1: my children are in that space. So yeah, they that
44:00
Speaker 1: they benefit. So you walked us very nicely into the
44:03
Speaker 1: topic that Coursera, and you've said something once in various
44:07
Speaker 1: conversations we've had that that made me sit up. In
44:10
Speaker 1: this world of drug pricing, et cetera. You said something
44:13
Speaker 1: which I'm sure you'll get to, but do you want
44:16
Speaker 1: to tell us about Coursera and what you're trying to do?
44:18
Speaker 1: You kind of hinted to it. But let's just because
44:21
Speaker 1: I find that amazing. Everybody is looking for prevention, nobody
44:25
Speaker 1: knows how to fund it or how to find patients.
44:28
Speaker 1: Took us through this, and you know you look the
44:31
Speaker 1: two of you together. I know Andrew Max was one
44:33
Speaker 1: of your drugs, right, So you do have a history
44:36
Speaker 1: of cardiovascular and you have Clive meanwell there who has
44:39
Speaker 1: just finished? I think maybe the ink has dried on
44:43
Speaker 1: the check already, the check. Yeah, So it took us
44:48
Speaker 1: through that.
44:48
Speaker 2: Please, well it's a remarkable story. I mean, we're developing
44:53
Speaker 2: a once annual preventive medicine that targets as a single product,
44:58
Speaker 2: targets both PCs can On for LDL lowering and engine
45:01
Speaker 2: ten synogen for blood pressure lowering. It's an RNAi based
45:06
Speaker 2: medicine because of the remarkable durability that one sees with
45:09
Speaker 2: you know RNI based approaches, and it's designed to be
45:13
Speaker 2: given to a population of otherwise healthy people who are
45:18
Speaker 2: at a lifetime risk of developing a future heart attack
45:21
Speaker 2: or strug using this AI predicted tool. The tool, the
45:25
Speaker 2: predictive tool, is called Clotho in honor of the one
45:29
Speaker 2: of the three Greek fates who determined does lifespan.
45:32
Speaker 1: There we go. You've got grease in here somehow.
45:34
Speaker 2: The exactly always have to have it. But the real
45:37
Speaker 2: focus is on prevention, prevention of future cardibasker disease. In fact,
45:43
Speaker 2: the company's vision is a world without cardivasker disease. A
45:46
Speaker 2: very bold vision to say the least, but one, frankly,
45:50
Speaker 2: Sam that is completely achievable. We have the tools, we
45:54
Speaker 2: know how we can lower the risk factors and acuative
45:57
Speaker 2: exposure to you know LDL into blood pressure. We know
46:01
Speaker 2: that if we do that, we can prevent future cardiovascar
46:04
Speaker 2: events from happening in the first place. But very importantly,
46:07
Speaker 2: we also need to lower the dish utility of a
46:10
Speaker 2: preventive medicine, and one way we're doing that is by
46:12
Speaker 2: having a once annual treatment as opposed to a more
46:15
Speaker 2: frequent treatment like a daily pill. The other way we're
46:18
Speaker 2: doing it is on the access side. We're thinking about
46:21
Speaker 2: pricing that would be acceptable for a prevention indication, something
46:26
Speaker 2: in the hundreds of dollars per dose, as opposed to
46:29
Speaker 2: the thousands or tens of thousands or hundreds of thousands
46:33
Speaker 2: of dollars that most specialty medicines are focused on. You
46:37
Speaker 2: can't do prevention if you're not focused on pricing that
46:41
Speaker 2: is almost vaccine like in its structure as compared to
46:45
Speaker 2: normal treatment based approaches, where one thinks of much higher
46:50
Speaker 2: prices because of the nature of those types of markets.
46:54
Speaker 2: At the end, but it's a powerful new company. We're
46:57
Speaker 2: very very excited about it, which is completed a series
47:00
Speaker 2: A financing, just announced it a couple of weeks ago,
47:03
Speaker 2: and we're already in the clinic with this with this approach,
47:06
Speaker 2: which is very very exciting.
47:08
Speaker 1: So where's the trial happening, and are you using the
47:11
Speaker 1: AI to identify the patients subjects?
47:14
Speaker 2: Yeah, right now, the patient right now, we're yeah, no, no,
47:17
Speaker 2: they're people normal, healthy people otherwise healthy. But it's being
47:20
Speaker 2: done in New Zealand right now. The phase one, the
47:23
Speaker 2: Phase three will be an outcome study, will be global.
47:26
Speaker 2: It'll it'll have you know, tens of thousands of people
47:29
Speaker 2: in it. Obviously, it'll you know, we'll use enrichment approaches,
47:33
Speaker 2: it'll use our clotho AI tool to identify people that
47:37
Speaker 2: are at high risk for developing CARDIOVASCU disease. So it'll
47:41
Speaker 2: be it'll be an exciting venture that'll start in just
47:45
Speaker 2: a couple of years at this point.
47:47
Speaker 1: Okay, So the timing sounds like if you start the
47:50
Speaker 1: phase three in a couple of years twenty twenty eight,
47:55
Speaker 1: let's say.
47:55
Speaker 2: Twenty eight, early twenty nine five to get the market,
48:00
Speaker 2: it will be on the market probably in the first
48:02
Speaker 2: half of the thirties.
48:04
Speaker 1: Right, that's about thirty four and with the without the
48:08
Speaker 1: outcomes data and the outcomes data.
48:10
Speaker 2: Oh with with the outcomes data in that time period.
48:12
Speaker 1: Okay, so you're going to choose subjects that are a
48:15
Speaker 1: little bit more at risk then I don't know, yes,
48:18
Speaker 1: Sam and John ten twenty years ago.
48:21
Speaker 2: Yeah, that's that's the that's the that's the goal we'll
48:24
Speaker 2: we'll we'll obviously enrich for higher event rate without impacting
48:29
Speaker 2: the labeling of the product. Obviously we'll align with the
48:33
Speaker 2: FDA on that, but without impacting the labeling of the
48:36
Speaker 2: product as it relates to being used in a broad population.
48:39
Speaker 2: At the end of the day, the enrichment is really
48:42
Speaker 2: a clinical trial tool, not an intended use tool.
48:44
Speaker 1: At the end, here's what I could be a tough
48:47
Speaker 1: question for you. Company Establishers goes to the clinic, IPOs, Pfizer, Novoality,
48:57
Speaker 1: any other company comes and buys it for five ten billion,
49:00
Speaker 1: excellent return for the investors. But then of course they
49:04
Speaker 1: might take a completely different view of the pricing model.
49:08
Speaker 1: What do you what do you? What do you do?
49:10
Speaker 2: Well? I mean, you know, Sam, our goal is to
49:13
Speaker 2: build this, to take it all the way. We do
49:16
Speaker 2: think we can commercialize medicines in the space because the
49:19
Speaker 2: model for commercialization is probably more of a direct to
49:22
Speaker 2: consumer based approach. Obviously the pricing is consistent with potential
49:26
Speaker 2: for out of pocket payment by individuals. But of course
49:31
Speaker 2: when we go public, we'll have piduciary duty to a
49:34
Speaker 2: larger number of shareholders, and we'll do what we have
49:36
Speaker 2: to do. But we do believe that whoever would buy
49:40
Speaker 2: this company would have to see the value in the
49:42
Speaker 2: model that we're building, and if they, if they somehow
49:45
Speaker 2: saw a different value or a different way of developing value,
49:49
Speaker 2: they'd have to convince our shareholders ultimately, But that is
49:52
Speaker 2: the better trajectory for the company versus the ones that
49:55
Speaker 2: we're building.
49:55
Speaker 1: Yeah, and as you rightly say, it would be out
49:58
Speaker 1: of your hands. There's another one in the last five
50:01
Speaker 1: minutes that we have another one in City Therapeutics that
50:05
Speaker 1: you are before before the as we're prepping you you
50:09
Speaker 1: said it'd be also a good one to talk about
50:12
Speaker 1: also in the S, S I R and A space.
50:14
Speaker 1: Do you want to talk us through that?
50:15
Speaker 2: Correct? Yes, A fascinating company. It's a It's a company
50:19
Speaker 2: that I hope will will lead the next generation of
50:23
Speaker 2: RNAi therapeutics because they're pioneering a technology that came out
50:27
Speaker 2: of a group of scientists katar and Achanichi at Ohio
50:30
Speaker 2: State and Phil's Amoor at the University of Massachusetts. One
50:34
Speaker 2: of the ONL. Milum founders around smaller double stranded RNA
50:39
Speaker 2: molecules that can mediate urn interference with a much smaller
50:44
Speaker 2: size of the so called trigger molecule. And the benefit
50:48
Speaker 2: of that is that these molecules have improved physical and
50:53
Speaker 2: chemical characteristics that allow them to potentially be more effective
50:57
Speaker 2: for extra hapathic delivery. So it's it's my belief that
51:01
Speaker 2: this company can pioneer leadership in the extra hapathic delivery
51:06
Speaker 2: space for RNAi in a way that others cannot because
51:10
Speaker 2: they're they're limited to these larger, canonical small interfering our
51:14
Speaker 2: name molecules. And so this is a company that we
51:17
Speaker 2: funded with Arch Ventures. It's raised about one hundred and
51:21
Speaker 2: thirty million dollars of a year and a half ago
51:23
Speaker 2: or so, really well capitalized. It's based here in Kendall
51:27
Speaker 2: Square and Cambridge and really off to a great start.
51:30
Speaker 2: First molecule has already made it into the clinic from
51:33
Speaker 2: this company in this company, and they should have two
51:35
Speaker 2: more i ds this year. So very exciting multi product company,
51:40
Speaker 2: just like Al Nalam. The goal is to have a
51:43
Speaker 2: portfolio of products that we that we continue to advance.
51:47
Speaker 2: Already have done two deals with this company, so really
51:50
Speaker 2: well on its way.
51:51
Speaker 1: That's exciting that these are so again going back to
51:54
Speaker 1: the starting point of a Nyland raising thirty million dollars
51:58
Speaker 1: in its IPO twenty twenty five, I mean, as inflation
52:03
Speaker 1: is this, is this one hundred and thirty million worth
52:06
Speaker 1: more than thirty million dollars in twenty two thousand and four.
52:10
Speaker 2: I wonder, well, I think it's an apples oranges comparison.
52:13
Speaker 2: I mean, when we did our IPO at two thousand
52:16
Speaker 2: and four, it was a very challenge market for IPOs,
52:19
Speaker 2: and everybody took a fifty percent haircut on their offering price,
52:23
Speaker 2: being aimed to raise more like ninety million or sixty million,
52:27
Speaker 2: seventy million, but we're only able to eke out thirty
52:31
Speaker 2: at the end of the day. It is what it is.
52:33
Speaker 2: In hindsight. I never looked back, but you know, for now,
52:37
Speaker 2: you know, companies like City Therapeut they can stand on
52:39
Speaker 2: the shoulders of the amylum giants out there and be
52:42
Speaker 2: in a better position to raise more capital because the
52:45
Speaker 2: science is more mature at this point in time than
52:48
Speaker 2: it was back then.
52:49
Speaker 1: So let's finish on twenty twenty six prognostications. Yeah, what
52:54
Speaker 1: are you looking forward? To twenty six, from your own
52:56
Speaker 1: companies or from the sector in general, from the from
53:01
Speaker 1: any area you want to touch on the capital markets,
53:04
Speaker 1: How you feeling, What do you feel city in Kindle Square.
53:08
Speaker 1: It's interesting.
53:10
Speaker 2: I mean, look, I'm hoping that we can continue the
53:16
Speaker 2: positive momentum in the sector that we saw, you know,
53:20
Speaker 2: come back a little bit in the second half of
53:22
Speaker 2: last year, where you know, the the you know, we've
53:26
Speaker 2: seen investor interests return, We've seen the XBI you know,
53:30
Speaker 2: returned to a robust level of evaluation and growth. You know,
53:34
Speaker 2: we've seen some great m and a happen that. Of course,
53:37
Speaker 2: this is a catalyst for investor interests in the sector,
53:41
Speaker 2: and my hope is that that continues in twenty six.
53:43
Speaker 2: I think it will. I think it will be a
53:44
Speaker 2: good year from a capital markets perspective.
53:47
Speaker 1: Is that the sense you get from the investors and
53:49
Speaker 1: bankers that you.
53:49
Speaker 2: Speak to, Yeah, bankers, investors, and I think it's all
53:53
Speaker 2: driven by the moderated investment interest rate environment here that
53:57
Speaker 2: that I think is favorable for for our sector, combined
54:01
Speaker 2: with a very long winter that has you know, finally
54:05
Speaker 2: shown signs of spring, and and the enthusiasm that usually
54:09
Speaker 2: comes with you know, with you know, with those green
54:11
Speaker 2: shoots that emerge in the sector. So I'm I'm optimistic
54:15
Speaker 2: about that, Sam. I say, the other thing that I'm
54:18
Speaker 2: hoping to see this year is more stability at the
54:21
Speaker 2: f d A. You know, it'd be great if we can,
54:23
Speaker 2: you know, have less turnover, you know, if the FDA
54:26
Speaker 2: can retool it's staff so that it can be best
54:30
Speaker 2: equipped to serve the companies it regulates, and and also
54:34
Speaker 2: to to effectively you know, avoid delays and drug reviews
54:38
Speaker 2: and approvals. That will be very, very important as well.
54:41
Speaker 2: And I think the third, and it was related to
54:44
Speaker 2: the first a little bit, is I do think there'll
54:46
Speaker 2: be quite a bit of M and A right coming forward.
54:49
Speaker 2: I mean, the the l OE issue for major pharma
54:52
Speaker 2: companies is profound, and the only way they can approach
54:56
Speaker 2: it is by accessing new innovation from biotech companies around
55:01
Speaker 2: the world. I mean, obviously we'll see that happen from
55:04
Speaker 2: China as well as in the US and Europe as well,
55:07
Speaker 2: but it'll be it'll be an important year for M
55:10
Speaker 2: and A without a doubt.
55:11
Speaker 1: Now, let me give you a couple of anecdotes here
55:13
Speaker 1: to make you feel better than even you do now
55:16
Speaker 1: in that on the FDA side, we had yesterday draft
55:21
Speaker 1: guidance about the use of minimum residual disease or measureable
55:26
Speaker 1: residual disease as an end point for multiple mile trials.
55:30
Speaker 1: This has been discussed before. The value that this has,
55:34
Speaker 1: obviously for the companies and patients, et cetera, is that
55:37
Speaker 1: this is despite the fact that I think everybody believed
55:40
Speaker 1: that Vina Prissad at Seber was against this idea. I
55:44
Speaker 1: think previously maybe there was things that were said before
55:48
Speaker 1: doctor Pissard was part of the FDA that would have
55:52
Speaker 1: suggested that he was against the idea of using MrDs
55:56
Speaker 1: as an endpoint. And here we are with the guidance
55:58
Speaker 1: document coming up, which is if you go and look
55:59
Speaker 1: at the share price moves in Legend and our SELX,
56:03
Speaker 1: that was what drove it. And at the same time,
56:06
Speaker 1: I think this year we get to truly test the
56:08
Speaker 1: commissioners of vouchers program to see whether they're actually making
56:12
Speaker 1: a difference to approvals. We've got some of those coming
56:15
Speaker 1: up with Johnson and Johnson's again my Loma. I'm sorry
56:18
Speaker 1: I keep talking about my momo because that's what I'm
56:19
Speaker 1: deeply looking at at the minute. But it's also got
56:22
Speaker 1: the good anecdotes for us, so that's all seemed to
56:25
Speaker 1: be going in the right direction. Fingers crossed. We'll see
56:27
Speaker 1: how that goes. John, This has been a fantastic conversation,
56:32
Speaker 1: even better than I thought it would be, and that
56:34
Speaker 1: was already high expectations. So thank you for joining. And
56:38
Speaker 1: you are a Sam, you are an example too many
56:42
Speaker 1: and I wish you every success with these companies. I
56:45
Speaker 1: will be very closely following Corsera and said the City
56:48
Speaker 1: Therapeutics for anything you involved in. So and I look
56:51
Speaker 1: forward to seeing you very soon.
56:53
Speaker 2: I do too as well, Sam, and we'll be talking
56:55
Speaker 2: i'm sure on the hangout at some point in the
56:57
Speaker 2: coming weeks, and I look forward to engaging with you
57:01
Speaker 2: throughout the year.
57:02
Speaker 1: Thanks for joining and see you soon.
57:05
Speaker 2: Bye all right, bye bye now