0:02

Hello and welcome to Raising Health, where

0:04

we explore the real challenges and enormous

0:06

opportunities facing entrepreneurs who are building the

0:08

future of health. I'm

0:15

Olivia. And I'm Chris. Today's

0:18

episode is with the co-founders of Tome

0:20

Biosciences, Rahul Kakkar, who serves as the

0:22

CEO of Tome, and John Fidd, the

0:24

CSO. They are joined

0:26

by Jorge Conde, General Partner of A16Z

0:28

Bio and Health. Rahul, John

0:31

and Jorge talk about the technology behind

0:33

Tome, known as PAST, a genome editing

0:35

technique. It's a combination of two

0:38

older technologies. What they

0:40

did is they used

0:42

a Cas9 nickase

0:44

with an RT enzyme that can

0:47

write small pieces. They

0:50

used that actually to programmably

0:53

write a landing site,

0:55

a beacon for

0:57

a highly specific

0:59

integrase protein. And

1:01

then they came in with the integrase protein

1:03

with a template DNA and then the integrase

1:05

does exactly what nature has evolved it to

1:07

do, which is to put that code

1:10

at that site. They also dive

1:12

deep into how this technology could be applied

1:14

to help patients, making cell therapy more accessible

1:16

for more people. Because

1:19

of the technical capabilities that John

1:21

just articulated, the ability to put

1:23

multiple pieces of code exactly where

1:25

you want them to go simultaneously,

1:27

we can bring design

1:30

make test cycle times that are

1:33

traditionally only thought of in the

1:36

biologic world to cell therapy. We've

1:38

never thought about being able to iterate cell

1:41

therapy design at speed and at scale, and

1:43

we can do that now. And so that

1:45

makes cell therapy look much less like a

1:47

niche product and much

1:49

more like a bonafide discovery platform. You're

1:52

listening to Raising Health from A16Z Bio and

1:55

Health. So

2:00

today I'm thrilled to be joined on

2:02

the A16Z Raising Health podcast by

2:04

Rahul Kakkar, who is the CEO

2:07

of Tone Biosciences and

2:09

John Finn, who is the Chief

2:11

Scientific Officer of Tone Biosciences. Tone

2:14

Biosciences is a portfolio company in the

2:16

A16Z Bio and Health portfolio. We're thrilled

2:18

to be a small part of the

2:21

tone story. I thought one place

2:23

where we could start is get

2:27

your views, your comments on where we

2:29

are on this journey of genomic

2:31

medicine. So where we stand today in

2:33

early 2024, we've just

2:35

come across a couple key milestones

2:37

in sort of the landscape of

2:39

genomic medicine. Maybe John, I'd

2:41

ask you to start first given that you've spent a lot

2:43

of time in this space. Just would

2:46

love to get your sort of take

2:48

on the state of the state. Yeah,

2:50

absolutely. So one of the

2:53

things just to actually let all

2:55

the listeners know upfront, one of

2:58

the things

3:01

about me that you'll be

3:03

able to tell is that I do have a

3:05

stutter. And I just want to let

3:07

everyone know what that means is that this

3:09

can take me a bit longer to say what I want

3:11

to say at times, but everything is fine. This is just

3:13

the way that I talk. Maybe one day

3:16

we'll be using CRISPR in the

3:18

brain for that. Not the first

3:20

indication, but anyway, everything is

3:22

fine. So when

3:24

I think about the state of the field

3:26

right now, it has come a

3:29

long way in a very short time. So

3:31

it was only about a decade ago that

3:33

the first publications came

3:36

out really on CRISPR

3:39

that really showed the ability

3:42

to site specifically target a

3:44

gene or a sequence

3:47

of code. That really

3:49

opened up the floodgates for everything

3:51

that we see now. And

3:54

I see that the CRISPR field has really

3:56

gone through a couple of different revolutions. The

4:00

first one was the ability to cut a

4:02

piece of DNA wherever you wanted.

4:04

This had a huge impact

4:06

both on life sciences, research,

4:08

understanding how life works, as

4:11

well as the first wave

4:13

of medicines. These

4:15

advances were all based on

4:18

the ability to site specifically break

4:20

DNA. Then came the

4:23

next wave of tools. You've got the

4:27

base editors, the prime editors. These

4:30

are fantastic tools that no longer break

4:32

DNA. If most of

4:34

the patients have the same mutation, this is

4:36

the right tool because if you make that

4:39

small change, if you fix that single mutation,

4:42

that will have a huge impact on that

4:44

entire population. What

4:47

we're doing here at home, I

4:50

see it as the last tool we've needed

4:52

in the editing toolbox. Now we can put

4:54

any sequence of code of any size in

4:56

any location. Yeah, and I

4:59

think when we take a look back, it

5:01

is remarkable that when we think about the

5:03

fact that this is a milestone, barely

5:06

a decade in the making given that the first CRISPR

5:08

papers came out just over a decade ago. Rahul,

5:11

first of all, you're a practicing physician. Second

5:14

of all, you're a repeat biotech

5:16

entrepreneur and executive. Of all

5:18

the things you could pick to work on, why

5:21

pick genomic medicine? Yeah, it's

5:23

a great question, Jorge. I did not

5:26

leave my prior company with the

5:28

intent to move into cell and

5:31

gene therapy or genomic medicines. My

5:34

clinical practice, as you mentioned, is

5:36

cardiology. My first company was a

5:38

cardiovascular-focused company. Second

5:40

company, Pandion, was autoimmune disease. I've

5:42

always focused on diseases

5:45

that have broad

5:47

societal burden and therefore where drug

5:50

development can have broad societal impact. And

5:53

to John's point, drug

5:56

development using either the first

5:58

generation or the first generation. of

6:00

CRISPR-Cas9 enzymes where we're breaking genes,

6:02

or the next generation, which is

6:04

really making small repairs, generally

6:07

lends itself to rare disease. And

6:10

it wasn't really a place, as much

6:12

as I don't want to take away from the gravity

6:14

of those diseases and the impact, particularly on children and

6:17

their families, just not where I've had my

6:19

focus. But becoming

6:22

familiar with the paste technology

6:24

as invented by our founders

6:27

struck me as something wholly different.

6:30

The augmentation of the CRISPR-Cas9 enzymes

6:32

with other enzymes so that it

6:34

can now not break genes or

6:37

make small repairs, but

6:40

wholesale reprogram DNA, allowing

6:42

us to really regard DNA

6:45

for what it is, which is software, and giving

6:47

us the tool to reprogram

6:50

a cell, which either

6:52

has a bug that nature unfortunately granted

6:54

it, or imparting new

6:56

therapeutic capabilities to a cell in

6:58

a dish struck me as

7:00

not just a step

7:02

forward, but

7:05

a quantum leap forward in creating a

7:07

whole new set of mature asset classes

7:09

of drug development. And

7:11

that potential societal

7:14

impact, which is broad by

7:16

definition, is really what attracted me to this technology

7:18

and to this company. So

7:20

I remember reading the

7:22

paste publication, and even as

7:24

a layperson thinking that

7:26

this seemed like a pretty

7:28

big step forward, like a pretty unique

7:31

innovation in and of itself. So

7:34

I guess the first thing that would be helpful is

7:36

if you could walk through what is

7:38

paste, what

7:40

was described in that publication. Now,

7:43

one of the remarkable

7:45

things about my story with Tome is that

7:48

I was not looking for a job. I

7:50

was very happy where I was. I was

7:52

working on next generation

7:54

delivery platforms. And so I took

7:56

the call with the founders, Omar

7:58

and Jonathan, as a favor. And

8:00

I thought they were doing something else

8:02

altogether. And when they said, no, actually,

8:05

Tom is doing programmable

8:07

genomic integration, I said, well, that's

8:10

been a holy grail of the

8:12

field since I started, and let

8:15

me see more. And so I read the

8:17

manuscript probably about two and a half years

8:19

ago now, honestly. And

8:21

as I read the manuscript, I had three

8:23

different emotions going on. So the

8:25

first one was I was super excited because

8:28

these guys solved the problem. And

8:30

the specific problem they solved was how

8:32

do you put a large piece of

8:35

DNA in a very specific location? My

8:37

second emotion was I was

8:39

actually jealous because it's such a good idea. And

8:41

next I'll actually talk about exactly what the

8:43

idea was. And then the third one,

8:46

I was getting sadder and sadder

8:48

because I love my old company, I love my

8:51

old team, but I knew if I

8:53

had the opportunity to be

8:56

a part of something like this, I

9:00

could not say no because this has been what I've

9:02

been trying to do

9:04

my whole career.

9:06

So what is it? Essentially,

9:09

it's a combination of two

9:11

older technologies. What they did

9:14

is they used

9:16

a Cas9 nickase with

9:18

an RT enzyme that can write small

9:21

pieces. They

9:24

used that actually to programmably

9:26

write a landing

9:29

site, a beacon for

9:32

a highly specific integrase

9:34

protein. And

9:37

then they came in with the integrase protein

9:39

with a template DNA and then the integrase

9:41

does exactly what nature has evolved it to

9:43

do, which is to put that code

9:45

at that site. And

9:47

so now for the first time,

9:49

the field could efficiently put large

9:51

pieces of code in very specific

9:54

locations without depending

9:56

on breaking DNA,

9:59

without depending on cells cycle. This works

10:01

in cycling cells, also works in non-dividing

10:03

cells, which is very important because most

10:05

of the cells in the body are

10:07

non-dividing cells. And so, when

10:09

I read this paper, it blew me

10:11

away. And when I had

10:13

the opportunity, I could not say no.

10:15

So Rahul, I want to hear your

10:17

sort of your story here because presumably

10:19

you came across the technology or the

10:21

founders maybe in that order and the

10:23

reverse order. And you know,

10:25

you had just come off of selling

10:27

your previous company. And so, there was

10:29

an alternative here which is to sit on the beach for a

10:32

little while and you didn't choose

10:34

that. So I just love to hear sort of

10:36

what got you interested and

10:38

engaged on this technology and

10:40

on these founders. Reading

10:43

the manuscript, I think I had

10:45

a somewhat

10:47

parallel epiphany, although for very different reasons

10:50

as John, which is here's

10:53

the chance to build a company

10:56

that can define an era in

10:58

medicine. And that kind of opportunity rarely

11:00

comes along. It comes along once

11:03

every few decades, if not once in a generation. And what

11:05

I mean by that is we can

11:07

think about the history of

11:09

our industry of

11:11

biopharma in certain eras.

11:13

The first era was really our ability

11:16

to create synthetic compounds. We

11:18

don't have to hunt and forage for

11:20

medicines anymore. And fast forward to the

11:23

rise of Genentech and

11:25

the cloning of insulin and

11:28

into the first fully human

11:30

antibody therapy which was Humira, which even

11:32

today is one of the largest commercial

11:35

successes in our industry. And

11:37

then there were three which is really

11:39

the rise of nucleotide therapeutics with companies

11:41

like Moderna and Alnylam. But

11:43

we have not seen the company

11:46

that will define genomic medicines

11:48

as of yet. For all

11:50

of the incredible scientific breakthroughs

11:52

that Sheppard-Pallier and Doudna, Fang

11:55

Zhang and David Lu had brought to the table, companies

11:58

including John alma mater, which

12:01

are developing very important drugs, the

12:03

ability to broadly mature an

12:06

entire technology

12:08

such that it impacts therapies

12:10

for a myriad of therapeutic areas. I

12:12

don't think we've seen the technology within

12:14

the genomic space that can do that.

12:18

And reading the paper and

12:20

then interacting with Jonathan and Omar,

12:23

I realized that what we might be looking at is

12:25

the technology in the company that actually does that. And

12:28

I think the founders have been key to this, Jonathan

12:30

and Omar, not just

12:32

being brilliant, of course, but

12:34

they really are invested in the

12:36

company with their time, with their

12:38

energy. They're

12:41

really seeing this as their way of leaving a mark on

12:43

the world. I just want to

12:45

dig in on a point that both

12:47

of you made, which is this ability

12:49

to do programmable genomic integration is

12:52

a massive step forward, a quantum leap, I think your whole

12:54

is referred to it as. Why

12:57

is that such an important enablement? What

12:59

does that allow us to do that

13:01

other approaches to genomic medicine just haven't

13:03

been able to achieve? So

13:07

to me, when you

13:09

can move from small edits

13:11

to wholesale inserting DNA

13:13

without any size restriction and

13:15

certainly without creating double

13:18

strand breaks, in layman's

13:20

term, making mincemeat of the DNA. So

13:23

to insert very large pieces

13:25

of genomic code in a

13:27

relatively safe manner, it really

13:29

allows you to utilize all

13:31

the various elements that nature

13:33

has encoded into our DNA,

13:36

coding regions, regulatory regions. We

13:38

can fully choose what

13:41

gene goes where, which

13:43

therefore dictates how much of the

13:45

genetic product is made, under

13:48

what regulation, in what cell, at

13:50

what time. It gives

13:52

us complete flexibility. For

13:55

lack of a better word, it allows us to hack the genome.

13:57

Yeah, if I could just add, I mean, one of

14:00

One of the applications

14:02

that I'm most

14:05

excited about is if a patient

14:08

has a broken gene, now we can put

14:11

a functional copy of the gene

14:13

in the right location. What's

14:15

funny is that when I told my wife that she's like,

14:17

well, what have you been doing for the past 20 years?

14:23

That's what everyone thought gene therapy was.

14:25

But we had to use Epizomes. We

14:27

had to use random integration, etc. But

14:29

now with this ability, not only can

14:31

we put the gene in the right

14:33

location so that it stays under its own

14:36

endogenous expression. Not too much, not too

14:39

little, not the wrong cell type,

14:41

etc. But we can

14:43

now have one product

14:45

for all the patients because we don't

14:47

have to go in and fix each

14:49

individual mutation. And for

14:52

most of the applications

14:54

that we're going after, there are

14:56

tens, hundreds, if not thousands of

14:58

separate mutations. And so with this

15:00

approach, we can cover most,

15:02

if not all, of the patients with a single

15:05

drug. That to me is

15:08

a total game changer. I wanted to highlight

15:10

something John just said, which is because of

15:12

the technical capabilities that John just articulated, the

15:15

ability to put multiple pieces of code

15:17

exactly where you want them to go

15:20

simultaneously, we can bring

15:23

design, make, test cycle times that

15:25

are traditionally only thought of in

15:27

the biologic world to cell

15:30

therapy. We've never thought about being

15:32

able to iterate cell therapy

15:34

design at speed and at scale. And we

15:36

can do that now. And so that makes

15:38

cell therapy look much less like a niche

15:41

product and much more like

15:43

a bona fide discovery platform. And

15:45

so to me, one of the

15:47

things that that tone would leave behind is

15:49

a legacy other than finally bringing gene

15:52

therapy into its mature form

15:55

is bringing cell therapy into its

15:57

to fulfill cell therapies potential as

15:59

a therapeutic. Four minutes? All right? I

16:01

think you just described our in terms

16:03

of what you can do for genetic

16:05

medicine in in the body is extraordinarily

16:07

profound. Because I just heard you say

16:09

there's. There's. Two fundamental things

16:12

that this technology enables that

16:14

become incredibly important: The. First

16:16

one. Is to be able to fix. A

16:19

broken gene regardless of what mutation broke

16:21

that team. So now we traditionally have

16:23

thought of a lot of these genetic

16:26

medicines as you need it, you know

16:28

and added to fix a specific mutation.

16:31

And. Hear what you're saying is you can

16:33

insert the corrected copy so you go

16:35

from one medicine permutation. To. One

16:37

medicine per jean. And I get

16:39

to very, very profound shift. But. The

16:42

second one I just heard you say,

16:44

which I think a lot of people

16:46

probably under appreciate. Is. The fact

16:48

that. Every gene in

16:50

our body is very carefully regulated

16:53

by the cells that they inhabit.

16:56

And. Soaps Different cells turn on

16:58

and off or turn up and

17:00

down different sets of jeans. And.

17:03

So if you can programatic, we insert

17:05

the corrected gene at exactly the right

17:08

spot. That. Means not only have you

17:10

corrected the problem. But. You've

17:12

also ensured that it is used

17:14

correctly within that cell type because

17:16

it's been regulated by that cell

17:18

type as nature intended. We.

17:20

Can harness any promoter in in

17:22

the body and so now I

17:24

shall we concert sort actually to

17:26

to have logic gates and gates

17:28

if this gets express and this

17:30

us to and that you know

17:32

that really might open up a

17:34

whole nother Rains have some suture

17:36

applications and so we're not limited

17:38

to wear discounts. What is kind

17:40

of remarkable was at at the

17:42

at a very fundamental level this

17:44

technology. It's a program and technology

17:46

is a programming language effectively as

17:48

what you are you working. On So.

17:51

In the case of a genetic disease, You.

17:54

Can essentially. Provide

17:56

patch software to replace a broken gene

17:58

with the corrected version. It

18:00

would really neat as you describe and it in the

18:03

case of cell therapy. What? You have

18:05

is the ability to fundamentally reprogram

18:07

cells. And reprogram sell to

18:09

behave in ways that perhaps weren't previously

18:11

possible. And. Can do things

18:13

that it with sophistication that weren't

18:15

previously achievable. In. The in the course

18:17

of cell therapy. And. So as you're describing

18:20

it, we get to a point where we have

18:22

a discovery platform of get to the you know.

18:24

To. The design build test time scale so

18:26

we can in a rapidly advanced technology.

18:29

A. Presumably that brings down cost

18:32

increases Access. That's obvious

18:34

he got to be seen, but that's that's a

18:36

potential promise. So. You can do

18:38

all of this both on. The.

18:40

Genetic Disease Front. In

18:43

terms of replacing broken jeans. And

18:45

on the cell therapy from in terms

18:48

of reprogramming cells to do new things.

18:51

You. Can do anything. But

18:53

you can't do everything. What? His

18:55

tone gonna do. So. When.

18:58

When. John and I first met you

19:00

before we decide to join the company.

19:03

Even. From are very first cup of

19:05

coffee together it was very clear that

19:08

were certain philosophical alignments. That. By

19:10

the end of that conversation my camera how

19:12

long it lasted. Maybe an hour, maybe two

19:14

hours. We both realized we had to work

19:17

together because your point where he this technology.

19:20

Can. Be the basis will be the

19:22

basis of a company that will last

19:24

decades and have a very large pipeline

19:26

in the future. But one of the

19:29

arts of Biotech start up is. Where

19:31

do you start when you're cost of capital

19:34

is very very high. And you

19:36

need to prove your technologies quickly as possible.

19:38

The As: every minute is hyper. And.

19:41

So remote concepts. Together we we actually

19:43

created a set of what what I

19:45

call first principles on how we're going

19:48

to select where we go. First.

19:51

Let's. Not take any more technical risk than

19:53

we have to write the tech. T.

19:56

G I and specifically the

19:58

instance of integrate. mediated PGI

20:00

or IPGI is complicated enough. It's one

20:03

of the most complicated drug products our

20:05

industry has ever envisioned. So let's make

20:07

sure we're not also taking for instance

20:10

delivery risk. Let's make sure

20:12

we're not taking inordinate clinical development risk

20:14

or regulatory risk. The

20:16

other place and this is again from my

20:19

experience at my prior to the basis, let's

20:21

make sure we go into clinical indications to

20:23

the point I just made where

20:25

the clinical risk is minimized. And

20:28

that means that there's some degree of target

20:30

validation. In the gene therapy world,

20:33

that's relatively straightforward. All you're doing is choosing

20:35

for diseases where there's a good genotype phenotype

20:37

correlation. But in the cell therapy world, that's

20:40

much harder. When I spoke with

20:42

the founders, when I you know read

20:44

the manuscript, I was

20:47

already working on new delivery systems. You

20:49

know how to get into new muscle,

20:51

CNS, etc. What I realized

20:54

that we already

20:56

have clinically validated delivery

20:59

systems available today that we can

21:01

use with this technology. And so

21:03

that's where we want to focus.

21:05

So the initial focus is going

21:07

to be on genetic diseases

21:10

of the liver? Yes. And

21:13

on autoimmune diseases? Yeah,

21:15

that's exactly right. So as we

21:18

think about not taking excessive technical

21:20

risk on the integrative gene therapy

21:22

side, it's really talking about focusing

21:24

on areas where delivery

21:26

of our components, which are

21:28

both lipinataparticle and viral vectors,

21:31

are already de-risked, which is the

21:33

hepatocyte specifically. Because even within the

21:35

liver, obviously, there's numerous cell types.

21:38

And going after diseases where

21:41

they're driven by genetic

21:44

mutations in or mutations

21:46

in genes that are expressed by the

21:48

hepatocyte, those diseases are

21:51

driven primarily by those mutations in the

21:53

hepatocyte itself, on the cell therapy

21:55

side, I Think

21:57

we take a step back and say, where does cell therapy.

22:00

The in the pantheon of the various

22:02

modalities that we have as we've talked

22:04

about already at again taking the lessons

22:06

of oncology are really the definitive area

22:08

where. Cell. And cell

22:10

therapies. Are proving themselves to be

22:12

superior to any other modalities. They can

22:14

really wipe out a cell with high

22:16

specificity and hi efficacy. On and

22:19

so that's really where we're focusing cell therapies and

22:21

and a blade of approach were there really isn't

22:23

good other option and we're starting with auto immune

22:25

disease. To the point to me before my first

22:27

industry job with Astra Zeneca. I'm had

22:30

acquired Human genome Sciences than list of Than and

22:32

A from a map. Great. The

22:34

state of the art was. Disease

22:36

Control and ten percent more patience

22:38

than Placebo. And that was. right?

22:40

That's like billion dollar plus revenue in the

22:43

autumn you space and fast for ten years

22:45

were talking about securing these diseases. This is

22:47

the kind of power that cell therapy can

22:49

bring, the tables, curing diseases that we thought

22:51

were barely controllable. past. As.

22:53

You all know better than I do.

22:55

It takes a long time to go

22:58

from paper the patience to two questions

23:00

for you. Number one. You recently announced

23:02

that you have acquired a company a

23:04

company called Replace Therapeutic. So.

23:06

At a good be helpful to understand

23:09

what replace brings to the table is

23:11

complimentary with the paste approach. And.

23:14

Number Two, I think it be helpful

23:16

for our listeners to understand where you

23:18

were. Tome is on the journey from

23:21

from paper to patients and one of

23:23

the saying things I think that was.

23:27

Surprising to me as I when I

23:29

first. Started. Started

23:32

at home movies from

23:34

from the. Manuscript.

23:37

Into medicine was a lot harder than I

23:39

had for spot. We

23:42

were able to replicate the founders

23:44

work no problem with a get

23:46

good efficiencies in cancer cells with

23:48

it gets seventy percent efficiency integration.

23:50

Fantastic! When we started moving into

23:52

primary human cells, non dividing human

23:55

cells, the actual cells we need

23:57

to actually it's actually worked with.

24:00

With. Reagents that look like medicine

24:02

or assistance used to have

24:04

to below one presets in

24:06

A took us a long

24:08

time to sue understand what

24:10

knobs we had to turn

24:12

to actually sissies, the clinically

24:14

relevant efficiency sees actually that

24:16

we have now and that

24:19

that was a lot of

24:21

different things on the guide

24:23

our in A the format,

24:25

the architecture, the chemical modifications,

24:27

the sequences that were targeting

24:29

with the enzymes. The architecture the

24:31

it's the the actual versions of

24:33

the enzymes excess are. So we

24:35

had to do a lot of

24:38

innovation there and along the way

24:40

we we've actually undercover some interest

24:42

in biology their think other people.

24:45

In a are no publishing on

24:47

but one of the reasons why

24:50

we're very excited about of. About

24:53

the acquisition of of for

24:55

places that brings on an

24:57

entirely new message of making

25:00

small others including like see

25:02

I'm. Reading. Beacon

25:04

were no longer news in and

25:06

sense to write and sequence were

25:09

actually providing the physical sequence we

25:11

want written and now we use

25:13

ally against actually to like a

25:15

that into the right place and

25:17

so if it's a completely different

25:19

mechanism to add to a John

25:21

said. I think about.

25:24

Crisper, Cast nine like a microprocessor.

25:27

It is a core piece

25:29

of technology that enables various

25:32

different products. right?

25:34

And if. The an

25:36

initial original embodiment of cutting

25:38

genes is akin to a

25:40

desktop computer. I. See

25:43

the. Modification.

25:46

Or. The augmentation. Of

25:48

Crisper cast nine with or without

25:50

reverse transcriptase his for be surprising

25:52

being a laptop. What?

25:56

Pz. I is still uses a microprocessor,

25:59

but it's been. so augmented and

26:01

enhanced with other enzymes, that

26:03

it's now an iPhone. And

26:05

it fundamentally enables a whole

26:07

new product class, asset class,

26:09

therapeutic class in this case,

26:13

and a whole new way of approaching

26:15

disease, a whole new application. To

26:18

me, replace then is the Apple Watch. It

26:22

has standalone functionality, but it

26:24

is also complementary to what we're already doing.

26:27

And so at Tome, we really think about

26:29

innovation in two different ways. There's internal

26:31

innovation and there's external innovation. We're

26:33

not going to spend, again, your

26:36

dollars, Jorge, and those of

26:38

you out there in the country, inventing things

26:41

that are being well-invented in the academia

26:44

or in delivery companies. That's

26:46

where we partner or acquire, depending

26:48

on the nuances of the relationship.

26:51

But there are areas where we are

26:53

coming across technical challenges that

26:55

really nobody else is working on. Integraces

26:58

is a good example. There are very

27:00

few places in this world, academia or

27:03

otherwise, that are really focusing on integraces.

27:05

And the amount of progress we've made

27:07

on increasing both the accuracy and

27:10

the efficiency of integraces, not

27:12

only have we created IP and

27:15

some of those powerful integraces in the world, I would

27:17

actually argue that we are probably the

27:20

most advanced integrase scientific group in

27:22

the world right now. Same

27:25

thing for some of the delivery technologies. We're not going to go

27:27

invent new lipids. But where there are viral

27:29

vectors that allow us to put 30,000 base

27:32

pairs into a cell, a problem that nobody else really

27:35

needs to even think about, that's where

27:37

we put our innovation dollars. So

27:40

our innovation is really the combination of partnering

27:42

and acquiring, but also inventing

27:45

internally where we

27:48

need to unlock certain technical barriers to

27:50

exploit the full potential of PGI. So

27:53

John, when I met you, you had

27:56

this glorious beard. Today

27:59

I see you. You have this

28:01

glorious beard. But. We've run into each

28:03

other a couple times and you had no beard. Do.

28:06

You have an exploration for that. Yeah,

28:09

thanks. So. It's

28:11

funny now and a pass pass a

28:13

it. Plaza you know I had

28:15

a seasonal baird and people can tell

28:17

with season a was based on my

28:19

face was ah hair and then at

28:21

home early days of tom someone someone

28:24

actually made a bet and said if

28:26

we head to certain milestones more you

28:28

do. I said I will save my

28:30

beard if we had this milestone and

28:32

in our i don't set easy milestones

28:34

because I like my beard and my

28:36

wife likes my beard and my kids

28:38

hate it when I sit. And

28:41

I'm actually happy to say over the

28:43

course of tom. Over the past

28:45

two is years I've I've

28:47

now save my beard three

28:49

times. That. I did propose a leadership

28:51

team at one point that when we cure our first

28:54

child using Pg either we all shave our heads, but

28:56

it didn't go over very well. That's

28:58

I would gladly do that. So

29:02

we all aspire to have a clean

29:04

shaven Johnson for all of the authors

29:06

his sister to the thank you both

29:08

for for being here today. Thank

29:19

you! Been listening to Raising It. Says

29:21

it introduced. I mean preset. Years. In and

29:24

Me Olivia Lab with the help of the

29:26

bio and health team and a sub Kinsey.

29:28

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