How This Biotech Entrepreneur Built A Multibillion-Dollar Company At Age 51

Forbes

Drug developer Suma Krishnan was 51 when she had the idea for a topical gene therapy to treat a rare and terrible skin disorder, called dystrophic epidermolysis bullosa, in which the skin becomes as fragile as butterfly wings. It was a risky move, as was her decision with her husband and cofounder Krish Krishnan to shun VC funding for their startup Krystal Biotech. Today, Pittsburgh-based Krystal, founded in 2016, is publicly traded, with a market cap of $4.1 billion, one FDA-approved therapy on the market and others in the works. “You have to be brave and bold to do this,” says Krishnan, an Indian immigrant who Forbes estimates is worth $287 million. “I was never afraid of risk-taking. I never felt like I needed a stable job.”  Read the full story on Forbes: https://www.forbes.com/50over50/  Subscribe to FORBES: https://www.youtube.com/user/Forbes?sub_confirmation=1  0:00 - Introduction: From Big Pharma Scientist to Biotech Founder 3:00 - Why We Avoided Venture Capital & Co-Founded as a Couple 5:22 - How We Succeeded Without Venture Capital 7:38 - From a $50M IPO to a $4.4B Company 10:14 - What is Epidermolysis Bullosa (EB)? 13:00 - The Science: How Our Topical Gene Therapy Works 15:33 - The 'Daunting' FDA Approval Process During COVID 17:51 - Beyond Skin: Applying Gene Therapy to Cystic Fibrosis & More 21:07 - What Patients Taught Me About Life 23:38 - I Never Would Have Imagined This Career 25:17 - My Advice for Young Women: Patience is Your Weapon  Fuel your success with Forbes. Gain unlimited access to premium journalism, including breaking news, groundbreaking in-depth reported stories, daily digests and more. Plus, members get a front-row seat at members-only events with leading thinkers and doers, access to premium video that can help you get ahead, an ad-light experience, early access to select products including NFT drops and more:  https://account.forbes.com/membership/?utm_source=youtube&utm_medium=display&utm_campaign=growth_non-sub_paid_subscribe_ytdescript  Stay Connected Forbes newsletters: https://newsletters.editorial.forbes.com Forbes on Facebook: http://fb.com/forbes Forbes Video on Twitter: http://www.twitter.com/forbes Forbes Video on Instagram: http://instagram.com/forbes More From Forbes:  http://forbes.com  Forbes covers the intersection of entrepreneurship, wealth, technology, business and lifestyle with a focus on people and success.

Transcript

00:00suma krishnan you are the co-founder and president of crystal biotech thank you so much for sitting

00:14down with forbes for the 50 over 50. thank you maggie for having me here so it's my pleasure

00:19you were 51 years old when you had the idea for a novel gene therapy a topical gene therapy treatment

00:27to address a really terrible skin disease can you take us back to that moment what was the light bulb

00:35idea for this therapy absolutely i'll go back to my journey as you can see my journey started 30

00:43some years ago i started as a lab scientist working in the lab making you know different products for

00:48different indications and i realized that lab is exciting but i wanted to see these products you

00:54know actually um get into the clinical studies and become uh you know approved for different

01:00indications so i moved from the lab into what is called development where we uh you know take the

01:07product that has a molecular hit to a particular indication and we start experimenting in animals

01:13and humans and then take it to a regulatory pathway so i started my career in pfizer and big pharma like

01:20johnson johnson johnson where i you know initially learned how to take these products then i realized

01:26like working for a big pharma it basically a pigeonhole and your ability to really expand and do what you

01:33want to do because i was a very curious person i wanted to learn and whatever i learned i wanted to

01:39make sure that i could actually incorporate and see products you know that i could be involved from all

01:45stages from early stage to all the way to approval sometime during my um during my uh in a tenure at

01:54intrixon i realized it came to me that you know what suma you've been working so hard developing drugs for

02:01someone else like you're i mean you have you come up with great ideas you invent it but it doesn't does

02:07not belong to you i mean this is you make other people rich it's not it's not a financial but also you

02:14know it's i mean you don't get the it's not the credit either but you you know you're not really

02:20ownership of the product you don't own the product because you're not you know the investor or or the

02:26main inventor because when you're inventor of that uh of a company the invention goes to the organization

02:33so at that stage i thought hard and i said i can do this myself i know it's a very risky thing

02:38uh and um but i had made enough financial you know uh uh gain from my past ventures and i was ready to

02:48risk the little money and take the risk to start um you know a new biotech taking my idea and building

02:57upon it so once i realized that i quit intrixon i had the the concept and the idea to treat this rare

03:03disease using a vector um you know that can deliver the genes for a skin specific disease

03:10the first thing i did is hired a lawyer file file the ip and then basically raised some friends and

03:17family money and started crystal biotech so that was the beginning of crystal biotech that's such an

03:23interesting journey so did crystal come more from your desire to have ownership over a company and an idea

03:30or was it more because you had this idea for this topical gene therapy and then the company just kind

03:36of followed i think a little bit of both because um in the past i've seen the drugs that i've worked on

03:43so hard and i realized that maybe i want to do something with my concept and idea and take it from

03:50you know ground zero all the way to approval so a little bit of both and obviously uh in you know i

03:56didn't have the financial resources or the contacts or the connections to take the bold step to start

04:03something you know on my own but i think with my uh past two experiences prior to crystal i had more i

04:11had the um you know the opportunity to actually uh to get to know investors private investors public

04:18investors and they knew my journey and story and they and i mean they believed in me they knew what i

04:24could do because i think there was more uh visibility into my potential and my capability

04:30after taking a product from you know phase one to approval because it's not an easy path it's not an

04:36easy path we'll get into the fda approval process a little later absolutely so one of the things i

04:41wanted to ask you about the early days of crystal you co-founded this company with your husband correct

04:46and you largely avoided the world of venture capital can you talk about why you made that decision

04:52absolutely i think um we have seen in the past that or with other companies if you get venture capital

04:59involved they pretty much take over the company i mean they sit on your board they directionally run

05:05your company and that's exactly that what i did not want because i needed the freedom uh and the ability

05:11to you know really dictate where the direction of this company was and partly it was because i mean the

05:18disease that i pursued to work on i was very compassionate about it because i did work on

05:23this disease before i got to meet a lot of patients uh patient advocacy group and i actually connected

05:29with them and i realized you know how difficult this disease was so i really wanted to make sure that i

05:36had the freedom to really take this disease to completely from early stage to approval and be involved in

05:43it and if you venture capital it was involved and they would drive this you know the strategy of the

05:49company or may decide to sell the company or force you in a direction where your heart is not or your

05:55passion wants to lead you so i know i was fortunate enough because krish we are we have our very opposite

06:04skill sets i'm more of the developing the drug and taking it his ability is to uh take the company public

06:11raise money investor relationships because he had taken two companies public prior to crystal so we

06:18were a good partnership i mean i know people talk about husbands and wives working together and uh one

06:24of the biggest questions how how do you make this happen and we are not the only first couple if you

06:29see you know madrigal was a husband wife couple beyond tech was a husband wife couple so there's precedence

06:35of husband wives to work together and again i think because we again had

06:41very um you know complimentary skill sets we thought this is perfect for us to you know work

06:47together to help crystal and again krish is he knew my passion and my compassion for these patients and

06:54he really wanted to support me and be there to you know see my dreams of getting this product to

07:00these patients succeed we've seen other companies on the 50 over 50 who have a spouse as a co-founder or

07:07even a child as a co-founder so i don't see that as the risky part i think what seems a little risky

07:12is when you think about how capital intensive biotech can be foregoing venture capital feels like a big

07:18risk did it feel like that to you i mean honestly i didn't think much about it so initially when we

07:25started the company as i said as we self-invested we had some friends and family uh invest with us but we

07:32were very clear to them this is the money that you're going to lose chris was very clear 99.9

07:37percent you're going to lose this money so if you're willing to lose the money feel free to invest in

07:42us so there were a few of our friends and family who believed in us and did said it's okay it's you know

07:48she's so passionate about this disease we don't mind so again um with my because i oversaw the programs

07:55i was able to with a very limited budget i we didn't make many mistakes because of my experience

08:02i knew the path the problem with biotech is you have people maybe very talented or very i mean you

08:08have these brilliant scientists that come from academia but they don't have development experience

08:13so often uh you know they may go down a path which can be more arduous or more you know and they

08:19may do more animal studies than that's needed and they can burn capital because of not really having

08:25the experiencing or experience or understanding of drug development and i think that's something

08:31where arbitrage was able to thwart because i i mean i knew exactly what's needed enough to you know get it

08:38through the regulators to get into a phase one state and then and beyond so i think that saved us so i was

08:46very quickly able to um do enough studies with the finances raise i mean have a very uh you know

08:54strong uh scientist like but very focused very dedicated was willing to work hard we had a very

09:01small team of five to six people we were able to do all of the studies that were needed for a phase one

09:08ind get it into the clinic and i think once we got into clinic we had some very strong investors who had

09:14made a lot of money on us from our past you know um uh companies and they built these they knew my

09:22potential and they knew i mean they trusted in me so one of our investors said you know what don't we

09:28save me money we why don't you they advised us to go public right away and they were willing to

09:33you know uh support it well speaking of ipos you ipo'd so quickly you went public in 2017

09:41barely a year and a half after starting this company what drove that decision again i think

09:48we had enough money but we knew that was not enough to take it in uh take uh you know the product into

09:55the clinic uh and we had very strong we had a very strong investor who advised chris to say you know

10:02take this public and i'll support you so we um you know obviously uh chris you know this is his magic

10:10and his relationships he uh you know appointed he uh found a bank that was willing to uh work with us

10:17and i remember back in uh 20 2017 we started making the rounds so the bank took us to all the different

10:27investors some of them again we knew and we made our rounds uh to see if they would be willing to

10:33participate in the initial ipo so we were very fortunate we had a few of them that believed in us and we

10:39we didn't raise a lot of money i believe it was like you know 30 to 40 million i think we had no

10:45problem uh getting that money and we went ipo'd uh at a valuation of 50 to 60 million at that time

10:53and it gave us enough money to take us to the next step and what's the valuation today today today it's

10:59almost 4.4 billion 4.4 billion what's been the biggest learning as you've gone from 50 million to 4.4

11:07billion i think the biggest for me is i'm like a dog with a bone i knew that i have this product and i

11:16need to take it to the finish line so i think keeping focused i mean not getting distracted i mean obviously

11:23you know you can talk about once you have money you can start building and you know uh you know hiring

11:30more people and expanding upon it but that was not my um you know that is not me i wanted i was very i

11:38felt very responsible for the investors that had invested in the money so our philosophy was not just

11:45grow and expand and get bring office big offices and build we still stayed in the same little you know

11:51tiny little office space that we have we still are there even today in spite of being a 4.5 billion

11:56dollar company so we don't believe in all that so we i mean again we don't spend money on stuff that

12:02doesn't have value so we focused on making sure you know and a lot of the work was done in-house because

12:08again i had uh i mean because of my experience i basically wrote the investigational documents wrote

12:15protocols trained my teams i was not afraid of hiring young scientists with no experience but mentoring them

12:22i mean many of the guys who joined me earlier never worked in a biotech industry but they're very

12:28smart very bright willing to know willing to learn so and i was willing to teach them let's talk about

12:34the product but before we do i only referred to the disease broadly as a terrible skin disease can you

12:40explain exactly what this disease is and what it means for patients who are experiencing it absolutely

12:45uh so this is called uh epidermis bullosa the this disease is uh very rare genetic disease uh i we

12:55estimate around 2 000 2 000 to 4 000 patients in the u.s globally you could have 30 000 patients so this is

13:02a defect i mean basically um where you have a defect in your cold seven gene uh so you have like 22

13:10different collagen in your body so you have the genes are coded for producing all these different

13:16proteins that are different functions in your body and if you you know if it's any of those codings go

13:24wrong then you may not produce a protein that's necessary for certain functions in your body in this

13:29case it's a cold seven gene uh that is has the genetic mutation or a deletion as a result the protein

13:38collagen 7 is not produced it's either produced or the form of the protein that is produced is

13:44dysfunctional and it doesn't do what it's supposed to do what does collagen 7 do it does is basically

13:52your skin has two layers epidermis and dermis so epidermis is the top of the skin and the dermis is your

13:59layer below the skin so collagen 7 is secreted by your uh gene and it basically forms it uh you know

14:07forms these hair like fibrils so it's like a little hair like thread that threads your um top layer to

14:13the bottom layer so it basically holds the two layers together that's where your skin is intact so

14:19when these patients don't have collagen 7 you can imagine that that very needed um you know and what

14:26you call is anchoring fibrils that cold 7 produces is doesn't exist so the skin is sliding over each other

14:33that means a dermis and epidermis so even with a slight rub or any i mean slight disruption the skin

14:40starts separating out and they have this whole large open wounds on their skin so just brushing by another

14:47person or even just sitting i mean yes they can buy sitting friction and what does your invention do

14:56uh so what we do is obviously uh skin is a or it's a very tricky organ i mean so it's not easy to find

15:05a solution that you know that you can uh for fixing this problem because either they do skin grafts and

15:11those even those don't work because the grafts can be you know tricky and they need um surgery and stuff

15:17like that and still it's not a permanent solution because your skin turns over that's what it does like

15:22hair the skin turns over so these grafts may not even last so we had to find a piece so my goal was to

15:28find a easy solution that was painless and that can be easily applied with for on these patients on these

15:36open wounds because they can tolerate pain i mean these kids have heard patients tell me that i had one

15:41patient telling me see my pain is my friend the day when pain stops is when i know i'm dead so that's

15:47that's the life of these patients so you can you cannot have a product that will induce

15:52more pain on them so my thinking was how can i come up with a solution never done before it's a gene

15:58therapy that i can topically apply as a gel so again i um we used a virus called herpes virus where

16:05herpes is known for infecting skin so it's a very perfect virus but you can take a you know wild type

16:12herpes so we engineered the virus to uh remove all the bad components of the virus so that it doesn't

16:18infect and cause the disease and it caused give us enough you know uh space to insert the human gene

16:24the col7 gene so that's what we did and so this is what my scientists did we build the virus uh we

16:31engineered the virus inserted the col7 gene and now we have a virus that we can actually manufacture we

16:36can make large batches we can expand the this vector and we can make large amounts so they can and

16:43then we formulate into a gel so when there's an open wound we apply it on the open wound and then

16:48we bandage it and as the wound closes the new when the new skin forms the because the vector is on the

16:55virus is on top of the wounds it'll produce the collagen 7 and it corrects the skin and then it's not as

17:00fragile it's not as fragile and this is the therapy that has fda approval correct in two that in two years

17:07years ago um 2023 may of 2023 we got approval from the fda what was that process like how difficult

17:15was it it was a pretty uh daunting process because again uh topical gene therapy was never done before

17:21so we were trailblazers on that approach so it was a lot of working with the agency for them too it was

17:27new so figuring it out you know uh the clinical pathway the administration pathway the type of clinical

17:34studies the type of end points to show that the product is working was again novel so we had to

17:40work very closely with the agency and then are right in the middle of our pivotal tried with covert hitting

17:46us so that was another put a you know uh made it more challenging but you know i had a team that was

17:54focused and even through covert times through the we continued our clinical trials we were fortunate that

18:01we were able to all the patients on our trial we could i mean were uh i mean took extra precautions

18:08so they could be protected from covet i mean so that they could continue the trial and not interfere with

18:14the study and we could get the outcome so it was pretty challenging times through covet and again working

18:19with the regulators with the new approach of a topical uh you know gene therapy and the second most

18:26important the most important thing is again this is an administration that you weekly administer an open

18:31wound so i mean it cannot be done at uh in the in a in the clinic or at the hospital because these

18:37patients cannot travel every week so it was important for me to think about what what can i do to work

18:44with the agency to make sure such a therapy can be administered at home summa as you talk about going

18:50through the fda approval process for your therapy and breaking new ground i think about all the ways that

18:57entrepreneurs and inventors following in your footsteps can learn from that and create their

19:02own therapies i have a similar question as it relates to the actual gene therapy that you have

19:09created you mentioned that this disease affects 2 000 people it's relatively rare are there scientific

19:16findings and answers within this therapy that could be applied to other diseases that's a very good

19:22question obviously um as we learned uh more about our vector and uh you know how we were able to help

19:30this disease we realized uh this particular vector has multiple uh could be used across multiple different

19:37diseases so that's something we learned so much right i mean it's not just the skin cells um but the vector can

19:44also in you know uh be useful for lung for lung diseases or for cancer or for the eye

19:52because again um so these are the things that we learned in you know as we move this program forward

19:58so as we were uh you know as we were moving our skin program forward we started our scientists started

20:06working and investigating for other indications so yes the simple answer is yes because if you look at

20:14our pipeline we have now uh you know several clinical trials for multiple different diseases and

20:20indications so we figured that we can also use this vector that can be you know administered to the

20:28lung or it can be administered to the eye so basically we can treat other rare diseases with the same

20:36concept of a gene that is a defect or a mutation and is not producing the protein so we have a program in

20:44the lung for a rare disease called uh cystic fibrosis so the so for cystic fibrosis there are drugs that are

20:51available that are you know pretty effective but you know if you look at cystic fibrosis there's four

20:57different kinds of mutations for so for two different mutations there are existing drugs that can work on

21:03these patients but there are a particular mutation where these patients don't produce any protein there's

21:09nothing for them so there's a subset of uh cystic fibrosis patients there's nothing today in the market so

21:15again we figured that with our vector we can introduce this you know cystic fibrosis gene and can help that

21:22subset of population wow that would be transformational yes we're very excited we initiated our clinical trial

21:29pretty novel so instead of a gel now we can reformulate it into a into a nebulized form so we can use a

21:37simple nebulizer put this vector with the cftr gene and a patient can just nebulize it and they can get

21:44the vector directly into their lungs and then it can produce the protein right where it's supposed to be

21:50so we have initiated we are in the phase one phase two we've dosed a few patients and we are investigating

21:56it for that indication so that's an exciting early stages it's early stages but we have now pretty

22:03good uh strong safety data showing that this adult can be safe and we don't have to because again when

22:11we uh now it's in the lungs directly so again safety becomes a big part so we have established safety so

22:17now we have to move into the part of evaluating clinical efficacy so that's where we are with cystic fibrosis

22:23yeah we have a few questions for you that we ask everyone on the 50 over 50 and i'll start with this

22:28one is being over the age of 50 an advantage or disadvantage in your line of work uh i think a

22:35little bit of both obviously you age aging is never a fun process but i don't think about it i think when

22:42you have a passion and a desire and you're so uh i mean you see patients suffering it gives you a

22:48perspective in life you feel you're so lucky because i see uh you know the average expectancy of the

22:55disease in my uh in this is 30 to 35 because even if they don't die of eb they they have what is they

23:05die of squamous cell carcinoma because they get this fast going aggressive cancer because the skin

23:10turnover and constantly you know wounding and closing so yeah i hear i see my patients with squamous cell

23:17carcinoma and i see how strong they fight they don't give up i mean um they get it on the on their

23:24feet or the hands and this once they get the uh the you know uh indication and a positive biopsy

23:32it's rapid spread so i see them amputating their organs like they start amputating their legs

23:37sometimes their two hands and they still want to survive and they have the will to live so they teach me

23:44a lesson every day and it gives me life in perspective so every day on this planet for me

23:49is a gift so i look at it that way and it's changed my life and i feel i i've i mean they've made me a

23:56better person and i feel taught me lessons and every day is a gift every day is a gift when you were an

24:04early career scientist when you were in your 20s and 30s did you ever imagine your career after 50?

24:10no i would if you if you asked me i came here as an immigrant when i was 20 years old uh you know to

24:17go to grad school pretty poor with nothing you know and uh building and and again um you know i had no

24:25idea because when you work for a big pharma um it's uh you know very male dominant and you're a little

24:32scientist in the lab and you have all these big ambitions and if you look back i would never dream i

24:39would never have imagined that i would be sitting here and i would have a drug approved with my own

24:44company with my own ip building a concept no in a million years but what i would say is you know

24:52i have uh you know i'm a fighter and if i have a will i'll make it happen so i just i'm like as i said

24:59i'm a i'm a bulldog in a china shop i'll i have a goal and i'll just do it i'm not afraid so i think

25:08whereas i think my husband is a little more cautious and i'm a little more like i don't care

25:12so i think we balance out pretty well and i i just go for it and i don't think i mean i don't think of

25:20the risks the way you talk reminds me of how some 30 under 30s talk about their risk taking sometimes

25:30it's better to just go for it rather than overthink and when you get to the middle or later part of a

25:37career it's easy to think about all the ways something can go wrong but you ignore all the

25:41ways something can go wrong and just go for it exact i mean i do i mean of course um financially i i

25:47mean i'm not a person that needs a lot to survive because i've come from nothing and i can survive so i'm

25:53not afraid i think if you're not afraid to you know survive with that with the minimalistic then

26:00it's that's me so i'm not afraid of losing it all but as long as i'm enough to you know have a roof over

26:05me and enough to survive i'll be fine so i think having that attitude helped me so i was not afraid

26:13of losing it all but giving a shot so what's your advice to women in their 20s and 30s who either

26:20can't imagine their career over the age of 50 or who feel like they have to accomplish everything

26:25get all the fda approvals before they turn 40. that's a very good question because there are a lot

26:30of young girls who come to me because they've seen what i've done and um i'm a very i'm a i mean i'm not

26:37the normal path it's very unique i'm not an md i'm not you know uh somebody with a with the you know as

26:45i said the typical biopharmaceutical executives that you see or you know or inventors you see

26:52so again uh they look at me and they see they're they're pretty sometimes they say if you can do it

26:56can i do it so and i said of course but again i don't think you can you should you cannot be ambitious

27:04right from the get-go you cannot be 25 year old and say i want to do this i want to achieve this i want

27:09to make this it's it's a journey i think my advice is learn be humble learn learn as much as you can

27:18if you if you and leave all your ego out of the window and be able to do the most tasks that you

27:26feel can be mundane repetitive boring you have to do it because you have to be able to finish tasks

27:32so that's my advice just you know dig in learn as much because knowledge is your weapon the more you

27:39know the more the things that in choices or risks that you take becomes less riskier because if you

27:46feel like oh i spent maybe two months at it trust me it takes two years to sometimes to learn it's like

27:52you know it's two months may not be enough and if you you cannot be always be honest to yourself like

27:59do i really know the stuff you know you have to be honest about what you know and what you don't

28:04know and again patience how i mean endurance hard work and patience patience is very important

28:13patience it took me it took me 25 years to to do what i wanted so and i i attribute that to patience

28:22and working on several drugs before i could embark on my own i didn't do it after my first one

28:29because i knew that i didn't know enough and my chances of failing are higher or the chances of

28:35saying that hey at this point i should give up and not proceed anymore when to give up because then you

28:42can go to complete failure so it really took those prior experiences for me finally have ownership over

28:48your invention for me for me some people may get luckier but i had a little bit of i mean i luck is an

28:55important factor but it was not all luck it was a combination of a lot i would say a lot of hard

29:01work a lot of willingness to learn you know perseverance long hours discipline suma krishnan thank

29:10you so much for sitting down with forbes for the 50th year absolutely thank you for having me

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