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. It's

1:06

been far too long since I sat down with today's guest . In fact , it was 177

1:09

episodes of the Business of Biotech

1:12

ago when we last connected . I'm

1:14

Matt Pillar , this is the Business of Biotech , and

1:16

when we last spoke I was recording

1:19

from the spare bedroom of my house

1:21

while on COVID lockdown , while

1:24

Lineage Cell Therapeutics CEO

1:27

Brian Culley was trying to figure out how to keep

1:29

a dry AMD clinical trial

1:31

going in an elderly patient

1:33

population that either couldn't or simply

1:35

didn't want to go anywhere near a

1:37

hospital or clinic at the time , for valid

1:40

reasons . On that episode recording

1:42

during an unprecedented time , we did

1:45

a lot of pontificating

1:47

on how biotech might look different post-COVID

1:50

. At the time , biopharma was hailed

1:52

a hero on the heels of the COVID vaccine

1:55

and money was flowing to virtually

1:57

anyone with lab space and a hypothesis

1:59

. It didn't take long for both

2:01

of those things the hero status and

2:04

the money to dry up On

2:06

today's episode . We're going to learn how lineage

2:08

fared as Brian navigated the company

2:10

through post-COVID minefields

2:12

. We'll revisit our three-year-old

2:14

conversation and maybe reflect

2:17

a little bit on what we got right and wrong on

2:19

the regulatory and clinical fronts , and

2:21

we'll learn where lineage is going

2:23

next . Brian , welcome back

2:25

. It's great to see you .

2:27

It is my pleasure , Matt . Thanks for having me back

2:30

177 sessions

2:32

later . That sounds great . Congrats to you .

2:34

I'm telling you . Thank you , yeah . Yeah , it's been

2:37

quite a ride . I'm tired , I'm not going to lie

2:39

, I'm tired , but it's awesome

2:41

. I've enjoyed every minute of it and

2:45

, you know , it was kind of fun to be honest with you , like when , uh , when we started

2:47

talking about getting back together and recording

2:49

another podcast , I was like I'm going

2:51

to go revisit that , that episode that

2:53

we recorded so long ago . I believe it was like the

2:56

turn of the year 20 to 21 . It

2:58

was like when things were really hitting the fan in terms

3:00

of COVID and it was like

3:02

it was like opening up a time capsule

3:04

, like reviewing our conversation

3:07

, the things that we talked about that day , um

3:10

, the things that were happening , the things that

3:12

we thought might happen , uh , some

3:14

of which did , some of which didn't . And then just

3:16

how ? How one 80 , the industry

3:19

went , uh , almost directly on the heels

3:21

of COVID . It was , it was very interesting . I would encourage

3:23

anyone who , uh , who is listening

3:26

and want some of that context to reference

3:28

, to go back . I think it was episode 30 , you

3:30

know this'll be like two 200

3:32

something , you know . So it was quite a while

3:34

ago , but , um , at the time , as I

3:36

said , our conversation kind of centered on your

3:39

work , lineage's work , keeping

3:47

the Oprigen and , I believe , opc1 , the spinal . So Oprigen is the dry AMD candidate

3:50

and I believe at the time you were also maybe starting out on OPC1

3:52

spinal cord clinical trial . You can talk about

3:54

that a little bit too , or correct me if I'm wrong . And

3:58

, like I said , the premise of the conversation was like how are you

4:00

keeping these things going in the context of what's going

4:02

on in

4:04

that here and now ? So I thought maybe we'd

4:06

start there , brian , if

4:08

you could give us an update on

4:10

, maybe a refresher

4:13

on , where those candidates were

4:15

then and where they are now

4:17

.

4:19

Well , yeah , you've given

4:21

me a lovely opportunity because that was such

4:23

a long time ago that it's actually quite easy

4:26

to point to a tremendous

4:28

change and all the progress that's

4:30

been made . You know

4:32

, at that time , when we were , when we were dealing with COVID

4:35

, you know that that is and

4:37

was consuming for the organization

4:39

. But as I was thinking about it just now

4:41

, as you're speaking , you know , it occurs

4:43

to me that that just happened to be the name around

4:46

those challenges at that time . Making

4:49

new therapies is very difficult , takes

4:51

a long time . There's a lot of failure and

4:53

setbacks that occur in even the

4:55

best of circumstances . At that time

4:57

, the challenges were really COVID-related

5:00

, which were certainly extraordinary , but there

5:02

are always challenges , even in the best

5:04

of times and , you know , I think that's what makes

5:07

good companies and good management

5:09

teams successful , as they get tested

5:11

and challenged in really unusual ways . For

5:14

us , I think we were able to navigate

5:16

those difficult and challenging waters

5:18

in a very successful way , way

5:29

. We end up , at the end of 2021 , entering into a partnership

5:31

with Roche and Genentech for that dry AMD program . So you know , we'd gone from having

5:33

the challenge of getting people to

5:35

electively go and have optometry

5:39

appointments to get assessed for how they're

5:41

doing , to announcing what at

5:43

the time was the largest ever cell

5:46

therapy license deal outside

5:48

of a cancer program . And so

5:51

a lot happened with that program

5:53

. It's continued to go into another clinical

5:55

trial , which is running today , and

5:58

even just recently our

6:00

partners at Genentech announced

6:02

the 24-month follow-up

6:04

data from our trial

6:06

showing that people still had

6:08

gains in vision in a condition

6:11

where they should be losing , and had gains

6:13

in key layers of their retinal tissue

6:15

which they should be losing . So we

6:18

are essentially reversing what

6:20

is thought to be as an irreversible

6:22

degenerative condition . So massive

6:25

change from where we were three years ago , and

6:27

maybe some of that change is applicable

6:29

also to the spinal cord program . The

6:31

spinal cord program is in pretty rough shape , you know three

6:33

years ago , but we've made incredible strides

6:36

with the manufacturing , the purity

6:38

, the control and we even have an entirely

6:40

new device . So it's really been an

6:42

incredible few years . That's's probably

6:44

added a few gray hairs to to our

6:46

chins , but a great success with

6:48

our programs at that time .

6:50

Yeah , I want to stay there for a minute . Since

6:53

you brought up the Roche Genentech deal

6:55

, I got a couple of follow-up questions on

6:57

on what you just responded to , starting

6:59

with the Roche Genentech deal . So , as

7:02

you said that that I don't

7:04

know six or eight months probably after we

7:08

last recorded , if not a little bit longer , give

7:11

us some detail on how that came together

7:14

. There are a lot of companies in

7:16

this space who , you know , drool

7:18

. They salivate at visions

7:22

of dream you know of , of of deals like that

7:24

. So

7:28

, to the to the extent you're able or willing , can you share some , I guess , backstory on

7:30

how that deal ?

7:32

came together . Yeah , the the

7:35

the reason why it was

7:37

such a big deal for us

7:39

, not in just in terms of dollars , and I'll I'll

7:41

mention those but the credibility

7:44

that a big pharma partnership brings

7:46

to a company , the capabilities

7:48

that they can put into our program . I mean literally

7:51

doing things that we couldn't . In

7:53

some cases , even if we had the money , we couldn't do

7:55

some of the things that they are able to do . You're

7:57

talking about one of the greatest companies

7:59

in the world of ophthalmology . So

8:03

we offered a

8:06

company like Roche and their

8:08

Genentech branch . We

8:11

offered them something that they'd never seen before

8:13

, which is the ability

8:15

to halt the progression of

8:18

this degenerative disease dry

8:20

age-related macular degeneration

8:22

. The most advanced

8:24

programs today really just

8:26

do a small amount to

8:28

slow the disease and we were

8:30

really halting it in its tracks and we

8:33

were bringing back tissue , and

8:35

that's incredible , because human beings don't have that ability

8:37

naturally . So it was

8:39

clear that it was our therapy that was driving

8:41

these outcomes . So it wasn't a huge number

8:44

of patients , but they had such extraordinary

8:46

outcomes that Roche

8:48

wanted to learn more about what we were doing

8:50

. Of course , we went through the very rigorous

8:52

diligence process that Big

8:54

Pharma puts you through to understand

8:56

if they want a licensed program . They

8:59

kicked a lot of tires around manufacturing because

9:02

cell therapy manufacturing is very , very

9:04

difficult . Kicked a lot of tires around manufacturing because

9:06

cell therapy manufacturing is very , very difficult and ultimately

9:08

they ended up writing us a check for $50 million

9:10

on day one . We're eligible for another $620

9:14

million of success-based milestones

9:16

for making progress , and

9:26

then there are double-digit royalties that increase as certain sales thresholds are

9:28

met . So you know , in the aggregate it was an enormous and very normal deal , which

9:30

is great for an approach that is different

9:32

. I mean , people have tried cell therapy in a lot of

9:34

different ways in the past and there haven't

9:36

been very many successes . So we

9:38

really fly the flag about this relationship

9:40

being a success for our program

9:42

and for our approach and what it can mean to the

9:44

other things that we're doing .

9:46

Yeah , had you in

9:48

previous lives , previous

9:50

endeavors , experienced

9:53

the doing

9:55

of a deal like that before .

9:58

Yeah , I mean because before

10:00

I was a CEO , I actually was the vice

10:02

president of business development , so I was the tip

10:05

of the spear , so to speak , for licensed

10:07

deals between small companies and large

10:09

companies . I've worked on deals

10:12

that you know all they needed was a signature

10:14

and you figured it was going to be done in a few days and

10:16

then I , you know , the company ended up getting

10:18

acquired by its parent and the deal was off . And

10:20

it's amazing , you know the journey

10:23

of getting deals done I've had , you know , the

10:25

big black escalades roll

10:27

up and all the people from Big Pharma pile

10:29

out and , you know , start going through all of your

10:31

documents in the war room that you set up for

10:33

them . It's a lot more virtual now and digital

10:36

now . But yeah , I've gone through

10:38

that experience and it's tough , especially

10:40

when they say no . You know they come and they look stuff

10:42

over and they say no , too risky or doesn't fit our pipeline

10:45

or whatever . It was very frustrating but

10:47

it was actually a fairly efficient

10:49

process . We're very impressed with our

10:51

, with our friends and colleagues over there at Genentech

10:54

in particular , and you know we're really excited

10:56

about this , this alliance , it's

11:00

moving forward and they continue to support

11:02

this program by electively

11:05

going out and talking about data

11:07

that's been collected and analyses that they've

11:09

found , and you know they don't have to do that

11:11

. So you know , from our perspective , we think that that's

11:13

a good indication that they're enthusiastic and

11:15

excited about what they're doing .

11:18

Yeah , yeah , that's really cool and the you know , the black escalades

11:21

and the war room is the color I was looking for . I'm curious

11:23

the black escalades and the uh and the war room is is the color I was looking

11:25

for I'm curious Uh and I'm sure I'm sure a lot of our audiences

11:28

, like you mentioned , they come in and they they

11:34

do a lot of due diligence , very detailed , kick a lot of tires . Can you give us

11:36

any more um , any more color or perspective

11:38

on like I asked you ? If you , if you'd seen this before

11:40

and you had , if you hadn't

11:42

like , what would you advise

11:44

someone in your role who hasn't

11:46

gone through a deal like that ? What would you advise

11:49

them to expect ?

11:52

I think it actually varies

11:54

. So there have been some instances

11:57

where companies that have

11:59

got you know big brands have

12:01

come in and they've been somewhat cursory

12:03

in their diligence . Now maybe that reflects

12:06

that they're just really kind

12:08

of deciding to do a different partnership and they're just box

12:10

checking on alternatives and they've

12:12

already decided . They're not that interested and just want some

12:14

confirmation of that . They usually

12:16

don't tell you if that's what they're

12:18

up to , but I've also gone through

12:21

really extensive processes

12:24

. So , for example , there's a big pharma

12:26

that was looking at this program that we were in touch

12:28

with literally for five years and they

12:30

were never discouraging . They just kept

12:32

saying this is very interesting , please stay in touch , this

12:34

is very interesting , please stay in touch . Year after

12:37

year , month after month . And

12:39

then somebody else ended up licensing it and

12:41

I think that that other company missed out

12:43

. So

12:49

you can have some deals that get pulled together very quickly for three or four

12:51

months because they just pour the resources into it . It's very intense

12:53

. Deals might go , you know , never close after years of

12:55

expectation and excitement . I

12:58

think if you can be organized

13:01

as a licensor , I think that

13:03

helps facilitate things . Don't

13:06

make it difficult for people to get information . Give them

13:08

access to your organization . If you're proud

13:10

of your program and you believe in it , it's going to pass muster

13:12

. You're not competing

13:14

with just theoretical programs , but you're also

13:16

competing with other things that they're

13:18

looking at . So you know , if you really want to

13:20

destroy the process , hide something that's a negative and then let them find it right . What a terrible

13:23

idea , because you really want to destroy the process . Hide something that's a negative and then

13:25

let them find it Right . What a terrible idea , because

13:27

you're going to lose credibility through the whole process . You

13:30

know , I would rather get in front of it and say

13:32

hey , here's what you're going to find , here's what we

13:34

think about it , and you know

13:36

there's no asset out there that's perfect , that

13:38

works perfectly , and so you know

13:40

you're going to have some deficiencies , and so I think it

13:43

helps those who are doing diligence If

13:45

you can say hey , I'd just like to walk you through

13:47

this so that you know in advance and

13:49

we build our diligence rooms like that we basically

13:52

have like a guide to the room . So it

13:54

was sort of like here's the program in totality

13:56

, and now for the regulatory expert

13:58

, here's sort of a written guide to kind of

14:00

walk you through the history of the regulatory

14:02

process . That

14:08

would be a different guide for the manufacturing person who's got to look through all of those

14:10

documents . It just makes their jobs easier and gets to answers faster . Because , think

14:12

about it , you're not moving your program forward while you're

14:14

going through diligence . Like you're focused on that diligence

14:16

and you know trying your best to

14:18

get good value out of that transaction

14:21

. So if you do a couple of those every year

14:23

, you know that's slowing down your company , so you want to make

14:25

them efficient .

14:26

Yeah , yeah , that's very good advice . You

14:29

mentioned also the other follow-up question

14:31

I had for you on sort of the high level recap

14:33

of those two clinical programs was around

14:36

the spinal cord program

14:38

and you mentioned that I

14:40

don't recall exactly what word you use , but

14:44

you alluded to

14:46

it not being in a very great place at

14:49

some point around

14:51

our last conversation on 21 . Tell

14:54

us about that and how you got that program resurrected

14:57

.

14:57

Yeah , I mean , if I were in the boardroom

14:59

I would say it's not commercially viable in

15:01

its current status . So there

15:04

are a number of problems with the program

15:06

. I don't think that the manufacturing

15:08

process was well controlled . The

15:11

purity was not where I thought it needed

15:13

to be , and these

15:15

aren't just you know , brian's ideas about

15:17

what a product should look like . You go

15:20

to the regulators and you look at expectations

15:22

and you go to the competitive landscape and you see what others

15:24

are doing and you can find out , you can really assess

15:26

whether you have a competitive product

15:28

or not . And so there were some deficiencies

15:30

in that product . Now , to be

15:32

clear , even with those deficiencies

15:35

, it had thrown off some very evocative

15:37

phase one data in patients with

15:39

spinal cord injury . So that's the

15:41

rationale is you see this really

15:43

cool data with an imperfect product

15:45

and you say , oh , this is great , now I want to fix

15:47

this product because I can only get it better

15:49

from here . And so that's really what we

15:51

did , was we took that product , we

15:54

went back to square one , we reimagined

15:56

what the process , development steps

15:59

, would look like , ie the recipe for how we

16:01

make the particular cells

16:03

that we use for those patients , and

16:06

we also looked at how they're delivered and we

16:08

noticed , for example , that the

16:10

old way of delivering the cells involved

16:12

this big apparatus that

16:14

was basically constructed above

16:17

the patient to hold a needle , and

16:19

you needed the patient to be immobilized

16:22

while you're pushing the cells

16:24

into the spinal cord . Well , you know

16:26

you have someone who's not breathing and

16:28

you're trying to administer very carefully

16:30

cells to just the right location . That's

16:33

not a great environment . So we

16:35

actually spent some of this last couple

16:37

of years identifying a new delivery

16:40

system which attaches directly

16:42

to the patient . So now the patient's

16:44

chest cavity is going up and down while

16:46

they're breathing and because that apparatus

16:48

is attached to the patient , not to the

16:50

bed , you can be delivering the

16:52

cells to the patient while they're still

16:55

connected to the respirator and breathing . So

16:57

it offers a really convenient

16:59

and more safe way

17:01

of delivering the cells . And so

17:03

these are improvements , and that's really

17:05

been . Our approach is to mature

17:08

this new field of cell therapy

17:10

out of more of an early

17:12

stage curious sort of maybe

17:15

I saw something cool in phase one and

17:17

move it into products that

17:19

can truly be commercially

17:21

successful , because you don't have to

17:23

plate and count the cells beforehand , you

17:25

can just thaw them and put them right in the patient . There's

17:28

so many places where you can make these products better

17:30

, and so that's what we did , was we invested in that

17:32

time . And it's very challenging as a business

17:34

because you're not rewarded for doing

17:36

that work until years later . But

17:39

if you don't do that work , it

17:41

inevitably is going to catch up with you , and

17:43

I think that's something that plagued a lot of the

17:45

early efforts in cell therapy .

17:47

Yeah , share a little bit , if

17:49

you would , about the

17:51

leadership that was required

17:54

to get the organization

17:56

behind that sort of you

17:59

know , as you put it reboot

18:01

right , let's go back to square one . Let's

18:04

, you know , let's reevaluate everything

18:06

that we did in process development

18:08

. Let's reevaluate delivery

18:10

, like those are , you know , those are big

18:12

things , like that's product , you

18:14

know , re-engineering , which

18:17

can be , you know , if not handled

18:19

correctly , I can imagine it would be pretty deflating to

18:21

a company and the team .

18:24

I'm saying like you know , if it's not done right

18:26

.

18:26

Like you need to maintain morale

18:28

momentum , you

18:31

know , on that project . So if you would just sort of share from an

18:33

organization on a leadership

18:35

standpoint what

18:37

went into right , keeping everyone

18:39

paddling in the same direction .

18:42

Yeah well , it can definitely be difficult because

18:45

the number of plates you have to keep spinning

18:47

with all the different competing incentives

18:50

. Each member board of directors

18:52

has a perspective and a voice

18:54

as to what you think , what they think

18:56

should be done . Every investor

18:59

who elects to reach out and have a voice

19:01

about what they think you're doing well or poorly . Certainly

19:04

, the team needs to be engaged and motivated

19:06

, and it has to be the right team , and so there

19:09

are so many competing factors that

19:11

it's almost impossible to sort of perfect

19:14

it . There's no place you can go to school

19:16

to learn how to do that trade of

19:18

, you know , moving an organization

19:21

through that process . But I do think what can be

19:23

helpful is to have a strong

19:25

and optimistic belief system

19:28

to reward success , to

19:30

not penalize failure

19:33

if it's tied

19:35

to things that are outside of people's control

19:37

. Right , If you only look at the scoreboard

19:40

and don't think about how the game went , you

19:43

might find yourself developing

19:45

a culture in your organization that

19:47

people are not enthusiastic about , and you might

19:49

lose some very high caliber individuals

19:51

. So , you know , I try

19:54

to get input from people

19:56

who are a lot smarter and a lot more experienced than me

19:58

, and then what I really try

20:00

to bring is just the synthesis of that information

20:03

to say , all right , based on a lot

20:05

of unknowns , probabilistically

20:07

, here's what I think we can do . Do we

20:09

have the capital or the access to capital

20:11

? Do this flow , this

20:13

work stream , yes or no ? Would it make sense

20:16

? When would we be rewarded for it ? So , integrating

20:19

in a cohesive manner all the many moving

20:21

parts and constantly updating that and

20:23

then providing that vision for what could happen

20:26

is definitely part of my job

20:28

. And I do think that

20:30

staff from the top of the organization to the

20:33

lower , more junior levels of the organization

20:35

can buy into that leadership

20:37

and be excited about it , because they might

20:39

not see that the

20:41

same number of things that I see from

20:43

the perch that I happen to sit in , the

20:46

same number of things that I see from the perch that I happen to sit in , you know , if

20:48

I convey that information into the organization , people say , oh , Brian

20:50

said X and that's why we're doing Y and

20:52

now I feel better about things . So

20:54

I think communication is really important

20:56

, I think optimism is really important and

20:59

I think you know being honest about where

21:01

you stand . You know sometimes you have to shut a program

21:03

down and people who have worked on it for

21:05

a long time might not like that , but if you

21:07

can walk them through why it's important

21:09

for the health of the company and the long-term success

21:12

, you know people usually get

21:14

there .

21:15

Yeah , yeah . And I mean in this

21:17

case you didn't shut

21:19

the program down . In fact

21:21

, like that leadership works both ways . Like you've got

21:23

to lead the troops but you also have to

21:25

sort of lead upline . You know

21:27

, I don't want to speculate , but to your point , like you have

21:29

shareholders and board members

21:32

, some of whom may be thinking like let's

21:34

ask this one . You know it's going to take too many resources

21:36

and too much time to get this back on track and

21:39

to re-engineer the program . So

22:03

so so two questions come out of that one like how do you lead upline ? How do you

22:05

, you know , how do you rally the folks who have decision making control

22:07

about ?

22:07

about pipeline decisions and two , when a when a

22:09

project is going to take a little bit more in terms of resources

22:12

and time than perhaps originally

22:14

anticipated , how do you

22:16

fund it ? Yeah , Especially

22:18

in a difficult you know the difficult

22:20

funding environment that we were pleasure of

22:22

the board , and so you know I do think about

22:25

you know I'm wanting the board to be very

22:27

happy with my performance , but you

22:30

know I've got thousands of other board

22:32

members and you know they're called investors and

22:34

you know there's social media . They , they have a voice

22:37

, even if they only own one share or a hundred

22:39

dollars of stock . Yeah

22:47

, they're usually the most vocal too , aren't they ? Yeah , they might be , yeah , and sometimes , unfortunately

22:49

, they might have the least amount of experience in the field , and that happens . But

22:51

they still can have , in many ways , an equal voice

22:53

to people who might own a million shares of our stock

22:56

. So you actually

22:58

find yourself having to manage in many directions

23:00

simultaneously . I'll

23:02

tell a short story . There was a program that

23:04

I thought was really

23:06

challenged . I wasn't particularly supportive

23:08

of , I didn't think it was right for the company

23:10

, and I got good advice from

23:12

a board member who said you know you're

23:15

approaching it in a way that you

23:17

think would resonate with you . Instead

23:20

of going through the approach that you think would make sense

23:22

to you , try this other

23:24

approach . And in this case it was basically

23:26

the data . So he said why don't

23:29

you go knock on 100 doors and

23:31

show that 100 out of 100 companies

23:34

weren't interested in partnering with you on this program

23:36

and then bring that data back ? So now it's not

23:38

Brian talking about Brian's opinion

23:41

, but Brian's experience . Good or bad

23:43

, this is just data . The data

23:45

says that 100 companies were not

23:47

interested in program X . Okay

23:50

, I think the data speaks . We don't do

23:52

program X anymore . So

23:54

there are many ways to

23:56

convince people

23:58

or to be persuasive , and one

24:00

way is not the right way . You have to kind

24:03

of be flexible and think about

24:05

your audience . It's the same with

24:07

funding , the second part of your question

24:09

. I often say around this organization

24:11

that you might have a great idea

24:13

I mean a really spectacular idea but we

24:16

can only do the work that

24:18

we can fund . So even

24:21

the greatest idea in the world , if it's not viewed

24:24

as a great idea by the investor community

24:26

, it's not going to happen because

24:28

there's not going to be capital available . So there

24:31

are constraints that are out there

24:33

in running an organization and if

24:35

you spend too quickly

24:37

, even on great ideas and you're not

24:39

keeping your head up and looking at the macroeconomic

24:41

environment , you may find yourself

24:44

destroying your company in a

24:46

financial way through its capitalization

24:48

structure that has nothing

24:50

to do with the fundamentals of your program . And similarly

24:53

, if you just sit around and you

24:55

wait , always for better days , like , oh , maybe

24:57

the stock will be higher tomorrow or next week or next

24:59

month or next quarter . The

25:02

world shifts and moves on , so you have

25:04

to be constantly paying attention to both

25:06

the micro and the macro and

25:08

factors that go far beyond the fundamentals

25:10

of your program . You got to tell people what you're

25:12

doing , or it's a tree falling in the woods . All of these

25:15

things come to play and make

25:17

this job and this activity

25:19

of developing new therapy is incredibly difficult

25:21

, but it

25:23

also is incredibly rewarding . You

25:26

sit with someone , for example , who has a spinal cord injury

25:28

and they say I'm really counting on

25:30

what you're doing , not for me you

25:32

won't be able to help me but someone like

25:34

me , and it's just I mean the chills

25:37

, right . And so you get up the next day and grind

25:39

like like you never grinded before , because

25:41

you're working for sort of a bigger

25:43

picture , big , bigger mission .

25:45

Yeah , yeah , how did you

25:47

say I mean you had , as you noted

25:49

, great news uh , end of 21,

25:51

. Uh on the on the dry

25:54

AMD um product

25:56

. How

26:02

, how did you like what you talk about the capitalization structure

26:04

? Was there a specific sort of strategy to uh to funding the

26:07

, the reboot of the spinal cord program

26:10

?

26:12

I think it was pretty straightforward at the time we

26:14

acquired it from another company , we knew

26:16

what the deficiencies were . I mean , we were the ones

26:18

doing the diligence , so we knew what we were getting into

26:20

and we basically made a

26:22

bet , a calculated bet

26:24

. And that calculated bet

26:26

was that our manufacturing team

26:29

that had been so successful with

26:31

the dry AMD program so successful

26:33

that they got a $50 million

26:35

upfront payment from Big Pharma for

26:37

their work we made

26:39

the calculated bet that they would

26:41

be able to do

26:43

similar successful

26:46

campaigns with the

26:48

allodendrocyte progenitor cells , ie

26:50

the cells of the spinal cord , and

26:54

they were . You know the data

26:56

that comes off of that program , the identity

26:58

of the cells , the consistency and control

27:00

of that program , the

27:02

RNA-seq data that we see when we compare

27:04

the old way of making the cells and the new way of making

27:07

the cells . It was a tremendous success

27:09

. So you know , very , very

27:11

happy with how we were

27:13

able to do that transition

27:16

from that program and really that's the long-term

27:18

goal . I mean , there's no reason

27:20

that transplanting retina cells

27:23

and pulling vision back in

27:25

the condition of dry AMD . There's no reason to believe

27:27

that that's the only place in the body where that kind back in the condition of dry AMD . There's no reason to believe that that's the only place

27:29

in the body where that kind of cell therapy can work

27:31

. It shouldn't be limited to

27:33

just the eye and the spinal cord . And

27:36

so if we can apply what

27:38

we bring on the manufacturing

27:40

side and the process development side , and our

27:42

ability to control the differentiation of

27:44

cells and the lineage of cells

27:46

, that is something that we could apply

27:49

in a lot of places , and so we might be able to multiply

27:51

our success . And that really is how to

27:53

build a big , sustainable company

27:55

, rather than just , you know , lucking

27:58

your way into one asset that got a pharma

28:00

deal and you know , hoping that years later it

28:02

ends up throwing out you know , royalties

28:05

. For you right ? You've got to keep moving

28:07

forward and build on the technology and the lessons

28:10

and keep your advantage , your competitive advantage , over

28:12

others .

28:13

Yeah , yeah , that's a

28:15

. That's a great segue to another question

28:17

I had for you . I'm I had in

28:19

my head sort of a , you know , a

28:21

linear chronology , a linear approach

28:23

to this interview , but now we're now , now , now it's

28:25

now , I'm moving all over the place , cause

28:28

you just gave me , gave me , a good segue to

28:30

another point that you and I discussed when

28:32

we last spoken . You

28:35

know , I mean it could be taken as a

28:37

sort of a great one of those great big , audacious

28:39

, bold statements right From a biotech

28:41

CEO when he says you

28:44

know , we , we , we envision

28:46

becoming the Amazon

28:48

of cell therapy , right , like

28:50

having a product for everything

28:53

rolling out of our platform

28:55

. And you do have

28:57

programs , as we

28:59

noted , and spinal cord and

29:02

ocular indications

29:04

, and also auditory , right

29:06

, you've got a candidate in the works

29:08

that's related to hearing

29:10

. What else , I

29:13

guess , what else would you see ? You know , if you , if you were going

29:15

to , if you're going to dub

29:17

yourself the Jeff Bezos of , of

29:19

of cell therapy , what

29:22

other areas do you do ? You look at and you go

29:25

. There's no reason , like you just said , there's

29:27

no reason why this approach shouldn't

29:29

work here or here or here , and

29:32

I know this , I'm treading into potentially

29:34

dangerous water . I don't want you to make any

29:36

announcements that you shouldn't be making .

29:37

Not at all . No , you're totally fine

29:40

. I welcome the question because we should

29:42

be clear about

29:44

the analogy , because there are some

29:46

people out there who didn't understand the analogy

29:48

and completely missed the point and thought that I said

29:50

that we would be as big as Amazon and

29:52

Amazon is like 10 or 15

29:54

Pfizer's . We clearly

29:57

were not going to be Amazon

29:59

in terms of the same size . The point

30:02

of the analogy is that Amazon began

30:04

as a bookseller , but

30:06

they weren't book experts

30:09

. They were delivery experts

30:11

and they were able to move what they

30:13

learned and what they were really good at in

30:15

logistics and delivery into

30:18

selling everything . The

30:20

analogy is that we

30:22

started with an ophthalmology

30:25

program . We got a big farm partnership for

30:27

an ophthalmology program that continues to

30:29

advance and it looks incredibly exciting , but we're

30:31

not ophthalmology experts . We're

30:33

cell transplant experts . So

30:35

the point is scale . The point is

30:38

that we have value inherent in an

30:40

approach that can scale

30:42

and go into other areas , just

30:44

as Amazon migrated from books

30:46

to every widget imaginable

30:49

and , frankly , no matter how

30:51

big this company ultimately becomes

30:54

, I'm not sure there are many companies

30:56

that even have a shot at it

30:58

. I don't know who has a deeper and more advanced pipeline

31:00

outside of cancer

31:03

cell therapy . Cancer cell therapy is very

31:05

established . Of cancer cell therapy , right

31:07

, cancer cell therapy is very established . As

31:13

soon as you move out of oncology but you stay within cell therapy , you know we're essentially

31:15

a growing center of excellence and I'm not aware of anyone

31:17

who's got a superior pipeline to

31:19

lineages in that way of

31:21

using cells , making them and

31:23

transplanting them to various parts of the body

31:26

cells making

31:28

them and transplanting them to various parts of the body . Now I do have the advantage that

31:30

I'm aware of undisclosed programs that we are evaluating

31:32

in various ways , and so I , you know

31:34

I can be more optimistic about the future perhaps

31:37

than others . But

31:39

that's really the point here is that there

31:41

are over 200 cell types in the

31:43

human body and from

31:45

a biological perspective , why would we think

31:47

that the retina is the only place you can find success

31:49

? My goodness , bone marrow transplants we've

31:51

been doing those for 60 or 70 years . They're

31:53

pretty darn successful . That's really

31:56

the same technology . We don't use undifferentiated

31:59

cells in human beings . We replace

32:01

the cells that are actually there

32:03

in the human being but they've been

32:05

damaged or absent in some way

32:08

. We're just replacing those cells and restoring

32:10

function .

32:12

In keeping with the Amazon analogy

32:14

? I'm curious about this and

32:17

you can tell me that it's in no way shape or form

32:19

in your plans , but

32:22

it makes me curious . When you have a platform

32:24

and you're

32:28

an expert at cell transplantation

32:30

and you subscribe

32:33

to at least some portion of the Amazon model , kind

32:35

of begs the question about , like the Amazon marketplace

32:38

, the marketplace element

32:40

of the Amazon model . I

32:42

mean , could you see a

32:44

future where lineage cell therapeutics

32:47

is the

32:50

expert in cell transplantation

32:52

for marketplace

32:54

members' cell therapy

32:56

programs for instance , like , do you see partnership

32:59

? You partnered upstream

33:01

, obviously with a Genentech deal

33:03

Do you see a future where perhaps

33:05

your partnerships expand sort of laterally

33:07

?

33:07

Yeah , yeah

33:11

, I think all analogies at some point

33:13

, you know , get stretched and start to break down

33:15

.

33:17

If I'm stretching and breaking here , just no , matt , that's

33:19

not what we're doing .

33:20

Yeah no , no , no . But I

33:22

understand the question and I think what

33:24

I would say is that , because

33:27

there are so many possible

33:29

indications and

33:31

applications for this technology

33:34

, it would be really

33:36

silly to think that we could pursue them all

33:38

. And so , yes

33:40

, partnerships are a great way to

33:42

do that . We

33:45

do not have a priori a

33:47

plan to partner every program , nor do we

33:49

have a priori a

33:52

plan to commercialize everything other than our first

33:54

program . Right that that is a a

33:56

business value creation

33:59

decision that gets made um

34:01

based on many , many factors . Right

34:03

, if you have good access to capital

34:05

at attractive prices , you're going to want to hold

34:08

on to your assets for longer

34:10

, create more value , before either

34:12

partnering them or becoming a commercial

34:14

entity . If you find

34:17

that the market for capital

34:20

is not attractive , then

34:22

you go elsewhere . And I think the last few

34:25

years in biotech , you know it was

34:27

very , very challenging . High interest rates is not

34:29

a favorable environment for biotech companies

34:31

, and you saw companies that had IPO'd

34:33

at , you know , at $20 and shot

34:35

up to $80 and then they came back to $5

34:38

. Well , when you raise money at $5 instead

34:40

of $80 , it's very expensive cost

34:42

of capital . So

34:44

I think that , on one hand , you have to

34:46

consider your partner strategy in

34:48

the context of your timelines

34:51

and the value that you're trying to create

34:53

and what's going on in your field

34:55

. But with respect to partnerships

34:57

as a standalone matter and smaller

34:59

partnerships or future partnerships , we

35:01

already struck one . We struck one

35:03

with the gene editing company , because , while

35:06

our current platform focuses

35:08

on replacing the cells that are

35:11

naturally found in the body , the

35:13

future of this field includes

35:15

cell engineering , meaning introducing

35:19

features and capabilities of cells

35:21

beyond those that are found naturally

35:24

. Maybe in some simple

35:26

and obvious cases , that would be something like

35:28

hypoimmune cell line . Right

35:30

, if you want to go outside of the ocular compartment

35:33

or the spinal cord , into areas where

35:35

you're fighting white blood cells with foreign

35:37

material , the right approach

35:39

there is to develop a hypoimmune cell

35:41

line , and so we and some other companies are

35:44

in that field . But

35:46

you can also imagine that there might

35:48

be properties in certain

35:51

conditions or diseases that would be beneficial

35:54

, that could either protect cells or give them enhanced

35:57

properties or enhanced durability , and

35:59

you could engineer those features into

36:01

cells . So that you know

36:04

, for example this is purely

36:06

theoretical a retina cell , that is

36:08

, a replacement retina cell , is a really great idea

36:10

and working well for us . But what if

36:12

we engineered a capability that that retina cell

36:14

somehow was a super performer

36:16

, and then we clone those and then we use those

36:19

and so maybe they're phagocytosing

36:21

material at a faster rate , or something like that

36:23

? That's the long-term big picture , and

36:25

you definitely need to have a lot of partners

36:27

to be working on and exploring all

36:30

of these , and so we are planting

36:32

those seeds . While we are looking forward

36:34

to the ongoing program in DryMD

36:36

to be successful and

36:38

hopefully make this company a lot more successful

36:40

than the work we've already done , we

36:43

are planting the seeds for the future

36:45

, increasing our capability

36:47

with the lines that we have available and

36:50

things like gene editing , so

36:52

that we can continue to maintain that

36:54

leadership position .

36:56

Yeah , yeah , very good . I

36:58

want to shift gears a little bit and talk about

37:00

hit on another point that we

37:02

spent quite a bit of time talking about a few years

37:05

ago . The last time that we met during COVID

37:07

, and that's that was the regulatory scene . I

37:10

mean , do you recall some of our conversation

37:12

around , like what was going on in

37:15

the regulatory environment during

37:17

COVID ?

37:17

Yeah , I think we did a good job predicting some

37:19

things , if I recall .

37:21

I think we did . I don't know . You know we'll see . It

37:24

was such an interesting time because , you know , on one

37:26

hand , I spent a lot of time talking to biotech

37:28

execs at that time during

37:30

that time who said you know , our clinical

37:32

trials are challenged by there

37:35

was this challenge aspect we're challenged by

37:37

regulatory attention . We're challenged to get

37:39

regulatory attention because

37:41

there was so much attention being spent

37:43

on the COVID vaccine and COVID

37:46

therapeutics . On the other

37:48

hand , you know , we were witnessing

37:51

this rapid increase

37:53

in the cadence of regulatory activity

37:55

simply because we were in a . You know what

37:57

is it ? Would it be DEFCON ? I think DEFCON

38:00

1 is more severe than DEFCON 5 . You

38:03

know we were in an emergency situation so

38:06

we talked a little bit about that . When we last spoke , you

38:09

know , we talked about the speed and agility

38:11

that we were seeing out of the regulatory

38:13

authorities . Speed and agility that we were seeing out of the regulatory authorities

38:15

and I believe you spoke in favorable terms about

38:17

your interactions with regulators

38:20

at the time . Do

38:22

you feel like any of that speed and agility

38:24

that was sort of

38:27

injected onto the scene during COVID

38:29

has stuck ? Has

38:34

it stuck around or are you seeing more of a sort of return to normalcy

38:37

, like what's ?

38:37

changed . Yeah , I think , more

38:40

return to normalcy than

38:46

a continuation of what we saw . I mean , I

38:49

got on the phone and for

38:52

a particular call about a technology that

38:55

was relevant to us in that period

38:57

and I remember there were representatives

38:59

from BARDA and DOD and NIH

39:02

and FDA , and you know I'm giving the presentation

39:04

to these very senior people , like

39:07

18 of them from all these different interdisciplinary

39:09

, you know , departments and divisions across the

39:11

government . Well , you know , now

39:14

our interactions are mostly limited to the project

39:16

manager for our spinal cord program

39:18

. So , you know , definitely

39:20

some things have gone back to normal . I think what

39:23

we saw is what

39:26

is possible and I felt

39:28

so proud , in

39:31

an extremely bipartisan way , that

39:34

what I saw was , you know , what America

39:36

is capable of doing , whether it's the

39:38

corporate side , the government side , the

39:40

human side . It's why

39:42

, when I watch the Olympics and I see

39:44

someone running in there in sixth place

39:46

but they've got a USA jersey I think they

39:49

might just win this thing , because there's

39:51

something about the DNA

39:53

in the United States that we find ways

39:55

of solving problems when really pressed

39:58

. But , being human beings

40:00

, you know we're fallible and we go back

40:02

to the normal ways . You know we're not great

40:05

at . You know thinking about

40:07

what statistical probabilities mean

40:09

and you know we fall back

40:11

into normal human patterns and psychology

40:14

. So I think a lot of things have

40:16

normalized and we've lost some

40:18

of those special programs that

40:20

existed for a very discreet purpose . But

40:23

I do think that when

40:25

we were talking , we spent a little bit of time specifically

40:28

on cell and gene therapy and I remember

40:30

making a call that we need to

40:32

see an increase , that the field is moving

40:35

very quickly and we need the FDA to continue

40:38

some of its aggressive

40:40

and rapid activity into

40:42

cell and gene therapy because otherwise it's going to get

40:45

too far ahead of the regulators and

40:47

they have . If you go onto the FDA website

40:49

and you look for cell and gene

40:51

therapy guidance since 2021

40:54

, there's

40:59

a very long list of stuff there

41:01

. So I think the push and the adoption

41:03

of new regulations and understanding

41:06

and expectations and criteria for monitoring

41:08

and manufacturing and delivering

41:10

cell and gene therapy product candidates has

41:13

been able to keep pace in a very

41:15

reasonable way . But you know

41:18

, when you're a government organization and you deal with an annual

41:20

budget and you've got elections

41:22

and everything , that's a very hard

41:24

thing to do . So I think you know

41:26

it's mixed , as it would expect

41:28

it to be . It's mixed results . You're never going to go

41:31

10x and maintain 10x forever

41:33

. It was great and encouraging to see that it was

41:35

possible , but I also

41:37

have seen the shifts into the right

41:40

areas of what the agency

41:42

believes is important and where the future

41:44

is headed , and that's a very promising sign

41:46

for us .

41:47

We need that kind of regulation

41:49

because it keeps the expectations high

41:51

for the sponsors like us the expectations

41:54

high for the sponsors like us , to

41:58

what do you , when you , when you look at that , you know that long and

42:00

growing list of guidances from the FDA since since 21, . You

42:03

know , beyond your call

42:05

for that on on my podcast

42:07

, which certainly , I'm sure , influenced

42:09

the FDA , I'm

42:13

certain of that .

42:14

The FDA .

42:15

I'm certain of that . Beyond that , to

42:17

what do you attribute the

42:20

attention that the agency has

42:22

placed and the work that they put into

42:24

creating those guidances and keeping

42:27

pace with the complexity and the technologies

42:29

that sponsors are dreaming

42:31

up every day ?

42:35

Yeah , the two things that come to my mind are one is sort of simply supply and demand . I mean , there's

42:37

this huge supply of new programs

42:39

. You know the

42:43

barriers to entry for gene

42:45

therapy perhaps are not , as you

42:47

know , extraordinary as they might be in some other

42:49

areas , and

42:51

so you've got a lot of new programs . There's thousands

42:54

of diseases and conditions to choose

42:56

from , and so I think it is

42:59

partly a response to the demand

43:01

from industry . You

43:03

know , if we're coming forward with cell and gene therapy programs

43:05

and you know the regulators , you know

43:08

that's what they need to staff up for . The

43:10

other is complexity . You know

43:12

small molecules are well understood . There's established

43:15

rules . Antibody is the same , but

43:17

the complexity of a living cell

43:20

is so many million times

43:22

beyond that which we're

43:24

accustomed to with small molecules

43:27

that it requires new

43:29

rules . I mean literally new rules . How are

43:31

we going to measure control ? You

43:34

say you're going to make this cell . What

43:37

defines that being that cell ? I sometimes

43:39

would say to people that we could

43:42

make something that's completely synthetic , as long as

43:44

it's safe and effective , normally

43:56

exist in the human body . That's not the criteria for a new product . The criteria for a new product

43:58

is around safety and efficacy . So I think those are the two drivers . There

44:00

is that there's been an incredible shift into

44:03

cell and gene therapy and so the regulators

44:05

and everybody , the payers , everybody in the

44:07

channel , everybody in that ecosystem has got to

44:09

be responsive to that . And then you

44:11

know , the old rules don't apply . If you apply

44:13

, you know , the standards of small molecules

44:16

to making cell therapy , it's

44:18

all going to fall apart . I would just joke

44:20

the dose . I get asked . Almost every

44:22

question I get asked about dose and

44:25

I always make the joke that you know I

44:27

don't know . I mean , if you put 100,000 cells

44:29

or 100 million cells into a person , how

44:31

many of them survived ? 100

44:33

million molecules of aspirin go

44:35

into your body ? Well , you know , we know what

44:38

happens to them , the cells they

44:40

can divide . They might not survive the

44:42

transplant . How many of them are going to graft and

44:44

be durable ? So dose immediately

44:46

is different . The second , you push the plunger on

44:48

the needle so the old rules of dose

44:51

response might break down in the SES

44:53

therapy . So you can

44:55

take that kind of analogy or comparison

44:57

as far as we need

44:59

, but I think that's really what the agency

45:01

is responding to is this is where the future

45:03

is headed and they need to be part of that and

45:05

ready for it .

45:07

Yeah , yeah , you

45:10

alluded earlier to the advantageous

45:12

position that you're in , alluded

45:16

earlier to the advantageous position that you're in knowing what you know about where lineage cell

45:18

therapeutics can go and perhaps will go , and you

45:21

know . Obviously you can't divulge all of

45:23

it , but I do believe there have been a

45:25

couple of publicly stated preclinical

45:27

programs added to the docket since

45:30

we last spoke . So what can you share

45:33

about , beyond the two very

45:35

active clinical programs right now

45:37

? What can you share about what's coming next

45:39

for lineage ?

45:42

Well , the two that I think you probably

45:44

have in mind since we last spoke are the photoreceptor

45:46

program , so we can manufacture

45:48

populations of photoreceptors , and

45:50

being that we operate in the eye

45:53

, photoreceptors is one of the

45:55

other major cell

45:57

types of the retina , and so it

45:59

would be natural that we would move

46:01

one step to the right from the RPE

46:04

cell to the photoreceptor cell . The

46:06

other program is called ANP1

46:08

, which is for auditory neuronal progenitors

46:10

, so

46:13

we're making the auditory neurons that pick

46:15

up the sound from the hair cells to

46:17

help people who have hearing loss . I

46:20

really like that program for a couple of reasons

46:23

. In particular , it shares a lot of

46:25

similarity with the dry AMD

46:27

program . Right , it's a relatively small

46:29

number of cells . They go to a very target

46:31

location . There's not a lot of competition out

46:34

there , as we just saw some from announcements

46:36

from you know , there's a big pharma that just

46:38

announced recently that some wonderful success

46:40

in modifying disease , and

46:43

essentially the headline was , you know , deaf

46:45

kids can hear again , and that's

46:47

really extraordinary . It shows you that this

46:49

massive problem with sensorineural

46:52

hearing loss can be modified

46:55

with

46:57

agents like ones that we are working

46:59

on , and so that's really exciting

47:01

, and this is a program that right

47:03

now is in functional

47:05

testing , right . So we're looking at hearing loss

47:07

in animal models . You

47:10

and I talked a few years ago and this program didn't even exist

47:12

. So what's really remarkable

47:14

here with what we are doing is that

47:16

we have the ability to

47:19

skip a lot of those traditional small

47:21

molecule steps . We don't have to develop

47:23

an assay that we hope is a validated

47:25

target screen 5 million small

47:28

molecules find hits

47:30

, develop those hits to leads , do structure

47:32

, activity , relationship and all the synthetic

47:34

organic chemistry that goes along with it to

47:36

try to finally get a small molecule

47:39

lead that starts going into

47:41

animal testing . We

47:43

went from sitting around the table and

47:45

deciding to go into hearing loss

47:47

to animal testing in

47:49

less than one year and less than a million

47:52

dollars . You cannot get that

47:54

kind of efficiency , and

47:56

so we have these really interesting advantages

47:58

with our approach that I think ultimately

48:01

are going to help this company be very successful

48:03

. Because the auditory

48:05

neuron is known , right , unlike a

48:07

small molecule where you have to figure

48:09

out how to get into the pocket and

48:11

inhibit this SH2

48:14

domain interaction

48:17

and everything , we just have to copy

48:19

what already is there . So we know what we're trying

48:21

to make . The auditory neuron

48:23

is deficient or destroyed . We're

48:25

going to replace it and inject it into the ear

48:28

. If it remains durable , if it remains

48:30

functional , it may be able to provide

48:32

activity in the form of hearing

48:34

, and so our ability to move very quickly

48:36

is one of the advantages , I think , of our

48:39

particular approach .

48:42

I hadn't planned on asking you this question

48:44

, but when you talk about efficiencies

48:46

and speed

48:48

in therapeutic

48:51

development specific to cell therapy , it

48:53

kind of begs the question in my mind

48:55

to what

48:57

degree lineage cell

49:00

therapeutics is concerned about thinking

49:02

about the

49:04

incredible patient

49:07

and payer cost of

49:10

cell therapy , like

49:12

in general . I would ask this question of any CEO

49:15

of a cell therapy company like um

49:18

, what , what

49:20

, what effect do you believe you

49:22

you can have , should have , maybe have

49:24

a responsibility to have around

49:27

, uh , reducing

49:29

the cost , the

49:31

, the , you know , the know , the end user cost

49:33

of these therapies via

49:36

, perhaps , efficiencies

49:39

in manufacturing ?

49:41

Yeah , it's the easiest question

49:43

in the world for me to answer . It

49:45

is that everything we do is allogeneic

49:48

. So

49:51

everything we're doing is going to harvest

49:54

cells from

49:56

a patient , spend weeks manipulating

49:59

those cells and reimplant those cells into

50:01

that same patient . That is a

50:03

bespoke therapy , that is a custom therapy

50:05

for one person , and so they're charging

50:08

$300,000 , $400,000

50:10

, $700,000 or millions in some cases of dollars

50:12

for that specific therapy

50:14

, because it's one therapy for one person

50:17

. It's incredibly inefficient

50:19

. If it does provide value

50:22

, you can get reimbursed

50:24

for it and there's a commercial opportunity

50:26

, but it is horribly inefficient . What

50:29

we do is we manufacture replacement

50:31

cells that can be mass

50:34

produced and delivered to

50:36

any of the patients . So when

50:38

we manufacture RPE cells , we're

50:41

manufacturing those cells in a bioreactor

50:43

. It's a closed system

50:45

. It can scale very easily

50:48

from where we are today . It's not on

50:50

. You know , you don't have a soccer

50:52

field filled with plastic plates and you have to have

50:54

people out there manually scraping the cells

50:56

. That's not what we do . We

50:59

have this one three-liter bioreactor

51:01

that can make 2,500

51:03

clinical courses in each

51:05

run and we have not even scratched

51:08

the surface on scale . Let's go to a 30-liter

51:10

bioreactor and see what happens . So

51:13

the really key advantage of an allergenic

51:16

therapy is exactly

51:18

that . These are pluripotent

51:20

stem cell lines . They

51:22

are self-renewing . So you

51:24

put the media on the cells , they divide

51:27

and they increase in number and , like that old thing about

51:29

you know , double a penny every day

51:31

. It's not very impressive in the first week , but in the

51:33

fourth week you're a billionaire . That's

51:36

the same . Principle here is that our starting

51:38

material is essentially endless and

51:41

then we put it through the process to manufacture the

51:43

specific cell type that we want and

51:45

our property to do that . And

51:47

having these off-shift therapies

51:49

means that we can really value

51:51

price our product and not get

51:53

crushed by how expensive it is with all

51:55

the handling and manipulation , and

51:57

that's why I think this company will be very successful

52:00

in the long run . We're

52:02

solving those problems now . We're investing in the

52:04

manufacturing and investing in the formulation

52:08

to be able to have those solutions , Because

52:10

ultimately those can dominate over

52:12

these autologous , patient-specific

52:14

therapies that are so expensive .

52:16

Yeah , all right , very good , we're

52:19

running short on time . Are you good for another

52:21

question or two ?

52:24

Yes , very good Good .

52:26

Also , since we last spoke , I read with

52:28

interest about some of your

52:30

associations , one

52:32

of them being the Spinal

52:35

Cord Injury Investor Symposium

52:37

, and the work that you're doing with the Christopher and

52:40

Dana Reeve Foundation . I mean , that's

52:42

you know , you throw the Christopher and Dana

52:44

Reeve Foundation and there you go . Okay , well , lineage

52:46

Cell Therapeutics is working in lockstep

52:48

with Superman . That's good company to

52:51

keep . But so it leads to the

52:54

question , like I'd like to hear about the relationship

52:57

there , but also how important , like

52:59

when you're working in a specific indication

53:02

area , like in this case , spinal cord injury how

53:04

important and strategic is it for companies

53:07

like Lineage Cell Therapeutics to establish

53:09

those relationships with patient advocacy

53:11

groups and foundations who work to

53:15

build awareness and therapeutic success

53:17

in those indications ?

53:21

I think it depends . I think a lot of companies

53:23

don't do it . So the conference

53:25

you're talking about is one that we created

53:27

in order to foster

53:29

and engender collaboration , because

53:32

my view is that many of the

53:35

companies that are working in spinal cord industry

53:37

or spinal cord injury rather

53:39

many of those companies have some common

53:42

problems , right , shared pain points . Not

53:44

all of us have the same pain points , but

53:46

there are certain things that are held in common . So , for

53:49

example , you know , there's the old commercial with Christopher

53:51

Reeve that was shown during a Super Bowl , where you know there's . There's this old commercial

53:53

with Christopher Reeve that was shown during a

53:55

super bowl , where you know he , he gets

53:57

some therapy and he can stand up , and you

54:00

know it doesn't need a wheelchair anymore . Um

54:02

, and it and it set expectations . Many people

54:04

, millions of people , saw that commercial and it set expectations

54:06

for what you know a therapy should do . But

54:09

if you , as I did yesterday

54:11

, if you spend time with a person who has lived experience

54:14

person

54:20

with a spinal cord injury , oftentimes they tell you just a little bit

54:22

more . I'd like to be able to clamp my hands a little bit tighter

54:24

around a stylus for my iPad

54:26

or a fork for my food

54:29

. People would

54:31

benefit . People with spinal cord injuries would

54:33

love to have just a little

54:35

bit more activity , mobility

54:37

, function , freedom , quality

54:40

of life . It's not about

54:42

throwing away the wheelchair

54:44

. And so that's a gap

54:46

, right , that's a gap between expectations and

54:48

reality , and every company working in spinal

54:51

cord injury shares that gap . So we can

54:53

work on that collaboratively and

54:56

that's what the conference has , in

54:58

part , been created to do . It's building

55:00

across some success that I had

55:02

personally in the world of sickle

55:05

cell anemia , where sickle

55:09

cell disease was not eligible

55:11

for one of these wonderful priority

55:13

review voucher programs , which

55:15

seems strange . I felt that it should have belonged

55:18

. So I got a bunch of companies together

55:20

and we worked together and we literally changed

55:22

the law and then President

55:24

Obama signed a law which added

55:26

sickle cell disease to the priority review voucher

55:29

program . So every company

55:31

in SCD benefited

55:33

from that . We all contributed to it and

55:35

it did nothing about competition . It didn't

55:37

matter if it was Pfizer or my

55:40

little company , we all could benefit

55:42

from that activity . So the conference is

55:44

aimed at identifying

55:47

and working on those shared pain

55:49

points , like endpoints and things

55:51

like that , in a way that is not

55:54

competitive . Like endpoints and things like that in a way that

55:56

is not competitive and it helps , at the same time , the investor community

55:58

to understand that there's a tremendous

56:00

opportunity . There's a big unmet need

56:02

, and so it does double duty for

56:05

the investor perspective . It's a one-stop

56:07

shop to learn everything they might need to know

56:09

and understand about the pros and cons and the opportunity

56:12

about investing in spinal cord injury , and

56:14

it allows us opportunities to have collaborative

56:16

conversations around , like combination

56:19

therapies or you know what could we work

56:21

on . So you wouldn't normally think of

56:23

you know going to a meeting

56:25

and finding you know AbbVie and

56:27

the Christopher Reeve Foundation and Lineage all

56:29

sitting around the table and laughing and having a grand

56:31

old time . But it's because we're working on

56:33

things that we all will benefit from

56:36

. Lineage just happens to have been the

56:38

genesis of this activity

56:40

, but we're really happy that others

56:42

are coming in and working on solutions

56:44

. It's just the kind of company we are

56:46

. I think it's a statement to the spinal cord

56:48

industry that we're important and

56:51

we care . So you know there's some beneficial branding

56:53

that goes along with it , but really it's about

56:55

trying to solve problems that we have in common

56:57

and engaging others in

56:59

those shared activities so that we

57:02

can be more successful as a field

57:04

which you might summarize as just saying making

57:06

the pie bigger .

57:07

Yeah , yeah . When is that symposium

57:09

?

57:10

It's coming up in San Diego June 26th

57:13

, 27th , and it's

57:15

great We've got an it to be

57:17

, you know , 100% around patients , although

57:36

their stories are probably the most powerful

57:38

part of the day , but really

57:41

about you know , hearing and seeing a lot

57:43

about what we need to work on in this field .

57:45

Yeah , very good . Yeah , it's an excellent

57:47

example of the company helping

57:50

to move the ball downfield in

57:52

an industry . You know , I

57:54

had a cool conversation not

57:56

so long ago with a friend of mine , paul Preeb

57:58

, who's been instrumental in

58:01

creating standards around single use

58:03

systems of all things , and he made

58:05

the comment around like if you're

58:07

ever in a situation where you're lamenting

58:10

the lack of something and

58:12

you say to yourself they need to do

58:14

something about that , he said you need

58:16

to look in the mirror and realize that you

58:18

are they . You know , and I think

58:20

this is it's an example . It's an example

58:22

of that mentality .

58:24

It's not always easy , right , because you pick up the phone

58:26

and you know you're calling a competitor

58:29

, right , and you're saying , hey , here's

58:31

an idea . I need you to trust me , I need

58:33

you to come to this event and you know , usually

58:36

it takes a year before people realize it's

58:38

a safe space . It's okay , right , there's

58:48

no trick here , you know , so we get there

58:50

. I think it'll continue to grow . I think it's

58:52

become wildly successful . The conference that we created in sickle

58:54

cell disease , I think , continues to this day . It's probably been 12 years since we started it . I've been out

58:56

of that space for a long time , but the need and demand

58:58

and the benefit of it shows you

59:00

why it continues to this day .

59:02

Yeah , yeah . Well , I hope it does find great success

59:04

, brian . What haven't I asked

59:06

you that I should have ?

59:12

Maybe what I'm so excited

59:14

about or why I believe in our technology

59:16

. I love talking about it .

59:19

Yeah , yeah , there's always that

59:21

. I mean you know it's clear throughout

59:24

the conversation . Your excitement is palpable . But

59:27

I mean that is a good you know . I wanted to ask you

59:29

what's sort of next for lineage , but

59:31

that's a you know part and parcel

59:33

with the question that you just asked . Like what , what

59:35

are you most excited about ? That's coming down

59:38

the pike .

59:40

Well , I think that the technology

59:42

itself I see signs

59:44

everywhere that that more and more , you

59:47

know , credible companies , credible investors

59:49

are investing in , in cell

59:51

transplants , especially outside of oncology

59:53

I mean oncology . Cell

59:56

therapy has revolution , has been a revolution

59:58

right , it's as strong and useful as as

1:00:00

chemo and surgery . And you know

1:00:02

, car T has been an incredible discovery . Now

1:00:06

people are starting to move outside of cancer

1:00:08

into other parts of the body and I

1:00:10

think there is going to be an enormous

1:00:12

wave of interest . And I see this at big

1:00:14

pharma companies . I see this at places like a Stelis and Bayer and Vertex . And I think there is going to be an enormous wave of interest . And I see this at big pharma companies , I see this

1:00:16

at places like Estella's and Bayer

1:00:18

and Vertex . And I see it in type one diabetes

1:00:21

and I see it in Parkinson's . And of course we

1:00:23

have the Roche deal with dry age related macular

1:00:25

degeneration , which is huge . And

1:00:27

when I , when I try to answer why

1:00:29

, like why is it happening ? I think partly it's

1:00:31

because the industry in the field has

1:00:34

matured , that we do have the ability to control

1:00:36

and scale these technologies

1:00:39

and maybe that wasn't present 10 or 15

1:00:41

years ago . So now we can actually have products

1:00:43

that generate revenue and of course , that always

1:00:46

interests investors . But

1:00:48

also I would say that , fundamentally , cells

1:00:51

can do things that small molecules and antibodies

1:00:53

cannot . So when you get to these diseases

1:00:55

, especially of , and

1:00:58

you start thinking about , oh , I'm going to use a small molecule

1:01:00

to treat this condition where

1:01:02

the whole cell is completely whacked

1:01:04

, you know there's thousands of things going wrong

1:01:07

and you're going to go tickle this one pathway . I

1:01:09

just don't think that's the right solution . So

1:01:11

, as we have an aging population and people

1:01:13

want to live better , maybe

1:01:15

replacing cells which has always

1:01:17

been the dream of cell therapy right , Organ

1:01:20

cells , tissues

1:01:26

how do we do that ? I think it's having its moment now , and so it's really

1:01:28

exciting to me personally to be a part of that , to literally be a leader in that

1:01:30

field and specifically for lineage

1:01:32

, although , of course , any forward-looking statement

1:01:35

that I might make , I would always refer people

1:01:37

to the risks of investing in lineage first

1:01:39

, which are all well-documented and

1:01:41

available online . But

1:01:43

we're really interested in seeing what

1:01:45

the ongoing clinical trial

1:01:47

of our lead program in dry AMD looks

1:01:50

like . That trial is being run by Roche

1:01:52

and Genentech and

1:01:54

when that information becomes available

1:01:58

or whatever updates they provide become available

1:02:00

. I think that'll be really interesting

1:02:02

because it's one thing for Brian

1:02:05

Culley to say we might

1:02:07

be onto something very special with this condition . It's

1:02:09

quite different to hear that from a company

1:02:12

with the experience and the depth and credibility

1:02:14

of a Roche and a Genentech with their innovation

1:02:16

. So I think that's something that's really exciting

1:02:18

. But we're going to just keep moving all of our programs

1:02:20

forward because this probably is a

1:02:22

new branch of medicine and we want to make sure that

1:02:24

we're pushing the field forward and ahead and being

1:02:26

successful with that . Yeah .

1:02:28

Well , I wish you luck . It's exciting

1:02:30

stuff . I thank

1:02:32

you for coming on with us today

1:02:34

, and let's

1:02:37

not go 177 episodes

1:02:39

before we next speak . How

1:02:41

about that ?

1:02:42

You start doing two episodes a day , it

1:02:44

might be perfect . I don't know . But

1:02:46

yeah , I think we should check

1:02:49

in from time to time because we make progress a lot faster

1:02:51

than every three years . So I'd be

1:02:53

delighted to come back when there's when there's some

1:02:55

, you know , really great stuff to talk about .

1:02:57

Yeah , well , it sounds like there will be plenty of material coming

1:03:00

down the pike . So , um , so , yeah , I'll

1:03:02

, I'll make sure I'll . I'll go on record right now and and

1:03:04

and and say I'll , I'll make sure of it

1:03:06

.

1:03:06

We will , uh , we'll we'll

1:03:19

get back together in a more timely fashion . Meantime , brian , good luck .

1:03:20

Best of luck on the symposium and all the great work that Lineage is doing and I look forward to the

1:03:22

next time we get to chat . I appreciate that , matt . Thanks so much for your

1:03:24

time . So

1:03:27

that's Lineage Cell Therapeutics CEO Brian Culley . I'm Matt Pillar and you just listened to the Business

1:03:29

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1:03:48

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