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I'm quite certain that schoolyard phrase which suggests the acceptance of torturous pain and even death before a vow be broken , was not derived from some kid's experience with the perinatal delivery of a drug to the back of the eyeball . But I'm also quite certain that it does fairly capture the prevailing sentiment about needles and their contact with eyeballs .
And I'm certain that , while biopharma has developed some amazing large molecule therapeutics for multiple diseases of the eye , the patient experience and thus adherence would be orders of magnitude better if their administration did not involve long needles plunged deep into eye sockets . I'm Matt Pillar , and my guest on today's episode of the Business of Biotech agrees .
His name is Clarke Atwell and he's a biopharma veteran who's spent the last 20 some years founding and leading companies focused largely on ophthalmology . He's currently leading ClarisBio as founding CEO , a company that's in a phase 1-2 trial of its lead candidate , a hepatocyte growth factor called CSB001 in patients with neurotrophic keratitis .
In patients with neurotrophic keratitis and you guessed it , the candidate is currently and hopefully will remain topically administered . Cross my heart , hope that I stick a needle in my eye . I interviewed Clark for Bioprocess Online a few months back and I enjoyed our visit so much that I just had to have him on the podcast to share his story .
Clark , it is great to see you and welcome to the business of biotech . Thank you very much . It's a pleasure to have you , and I want to start out by getting to know you a little bit and what inspired you to become an entrepreneur and founder in biotech .
Given that you started your career with some heavyweights Merck and Roche and directorial positions there before you jumped into your first startup . I think your first startup was Lux Biosciences . You can correct me if I'm wrong here , but generally , what inspired this pivot that you made away from big bio and into the murky depths of biotech ?
Well , it actually wasn't a pivot . So my father is a serial entrepreneur , my grandfather was a serial entrepreneur and I always wanted to be in a biotech a smaller company I applied to coming out of college .
After my master's I applied to Amgen and Genentech and at the time this is how old I am at the time they were small companies and when I called them at Amgen specifically , the head of HR said that they were hiring over 200 people and they were not over 200 people and they were not hiring people who didn't have any experience .
So she very wisely said that I should go learn my craft at a large pharma and I was very fortunate that Merck at the time hired a lot of people out of my master's program about eight people a year and so I joined Merck and the pivot there was that I had to actually reconsider whether I wanted to be an entrepreneur because Merck was such a great company .
When I was there , I was still under Dr Vagelos and it was just an amazing company . I did not go to an Ivy League school , but I imagine that the same level of intelligence and thoughtfulness and process would be at Harvard or MIT or something like that .
So I always walked into the room and felt I was the dumbest person in the room and I just continually learned every day when I was at Merck and it was just a pleasure to be there . So the real pivot was leaving . That was the harder thing to leave . Yeah , you said , your dad and your grandfather were entrepreneurs . Were they in life sciences as well ?
No , my grandfather was in electronics mostly and my father went from . There was no common theme . He would start . He was a stockbroker . He had a shipping company . We had a farm in Africa . We went all over the place .
Yeah , Well , I can see where those seeds were definitely planted there right . If your dad was a risk taker who was willing to plunge himself , you know , make such , you know lateral moves . It was kind of written on the wall for you , wasn't it ? Yeah , so it was .
Since you left Merck , what was , I guess , the inspiration for the attention that you've been focusing on ophthalmic diseases since you kind of charted this entrepreneurial path , I think ?
two things . I think the path there was immunology . When I was at Roche I was lucky enough to be on the team to launch CellCept in solid organ transplantation and I just I loved immunology . It was one of those areas that's still being discovered and there's lots of new . Everything changes .
You know , if you have Janeway's book of immunology you can pretty much throw it out and start again because they update it regularly and it was . It's a field that that changes dramatically and they're just learning so much about it and it touches so many aspects of or so many diseases or conditions in the body .
So I really enjoyed that and that was how , at Lux Biosciences , our first disease in the eye was uveitis , which is an autoimmune disease of the eye . But my introduction to ophthalmology came through a brief stint at iTech , which was David Geyer's company and it was his first company and it was eye-opening excuse the pun , but I enjoyed it very , very much .
And I came to the company through Merck alumni that brought me in and so I consulted there for about nine months and I really enjoyed it .
Yeah , Was it sort of a conscious ? You know ? I mean , I spend a lot of time talking with biotech leaders who don't necessarily marry themselves to a specific organ or a specific indication even , and then some who do you know , they decide that that's where they want to play and that's where they want to build their career , and it's a conscious decision .
Where do you kind of fall on that ? Do you feel like it was a conscious decision to go there and stay there ?
No , I don't think it's a conscious decision . I think there are a couple of things about ophthalmology that I like a lot . One is there are very few organs in the body that you can actually observe and you can actually see what you're doing and having an effect . So that is definitely a benefit .
The other benefit of ophthalmology is , as long as you're doing things that are just exclusive to the eye in the sense of delivery of drugs , you don't have to worry about first pass effect and all the other things that you do with a systemic drug , so your timelines are a little shorter in the eye .
And then the other thing I think that keeps you in a therapeutic area is you develop a network of colleagues , friends , people you trust and people who your team basically .
And I think you see that in a lot of companies where you you work with the same people over and over again because you trust each other , you finish , you finish each other sentences and I think that network kind of creates a gravity that keeps you in a therapeutic area .
But yeah , I've worked in infectious disease , uh , solid organ transplant , cardiovascular HIV , and I've enjoyed them all , because I enjoy the learning process and you learn so much when you're deep into an indication .
Yeah , have you found that there's any transfer , common threads from those other indications that you've worked in to ophthalmology or , I guess , learnings that you've taken away from some of those other experiences with you know , organ transplant and other indications that transfer well to the work that you do now ?
I think the thread of immunology is very , very helpful and a lot of the diseases we'll look at with HGF there is an immunological component . I think that the other elements I think are more from the patient side .
When I was fortunate enough to work on Crixivan at Merck , it was the early days of HIV and Merck , when they launched Crixivan , never really saw it as a product in the sense of it was going to drive revenue or profitability .
They kind of looked at it as more of a service and it was something that they had a capability in for the protease inhibitors and they worked to bring that forward .
And so the way they they worked with the community and their relationship with the community taught me a lot about how to how to work with patients and how to be thoughtful not you're not just making a drug , but you're also helping a patient population and how to look at it you , uh , you mentioned , you mentioned teams and sort of building momentum and having
some gravity around people in a space .
And when I think about the Claris bio origin story , I want to get that from you because I think about the doctors . I believe there were two Harvard researchers and I'll probably mispronounce their names , so correct me if I get these wrong , but Drs Reza , dana and Sunil . Chauhan Chauhan yes , yeah , chauhan .
Okay , so they were the hepatocyte growth factor researchers . That sort of became the nucleus of the molecule , I guess , for lack of a better way of putting it , tell me a little bit about their work and how it sort of well , tell me about their work and then we'll kind of talk about how that evolved into the buildup of a company of clarice bio yeah .
So I had met , uh , I had met dr reza dana at when I was at lux . He was a consultant to us and as uh , as we were developing our drug there and um , so I , I I got a call from him and he said would you , would you be interested in starting a company ? So I went to meet them and they had um .
So Reza Dan is a cornea specialist everything I'm talking about is in the cornea but he and Dr Sunil Chauhan were working with mesenchymal stem cells and they were seeing this very positive effect in the sense of prevention of fibrosis and acceleration of healing in several animal models that they were working on .
But they also realized that with applying cells to the surface of the eye was going to be tricky in the sense of what's your dose , how do you make them ? And then consistently make the same cells and then apply them to the eye .
They saw it was a regulatory minefield , which I think it would have been , but cleverly they looked at the secretome of the mesenchymal stem cells and said these are the top five or six proteins that are being produced and they went in and silenced them one by one . And it's when they silenced HGF that the effect of the cells basically went away .
And that was their aha moment , and that was when they discovered that it was HGF that was driving the salubrious effects of the cells . And so from there they methodically went through several animal models of injury and healing . But they also . What I thought was very satisfying when I met them is they'd spent a lot of time working on the mechanism of action .
And I think in the drug world at least my experience is in the package insert you always have the mechanism of action and there's a lot of hand waving there . And I would do at Merck , even at Merck , when we would put in the mechanism of action , it would , years later we'd learn more and more and more about what the real mechanism was .
But with , with , with , with raisins you know what they had done is because they are very , very curious people . They had gone through and systematically looked at the mechanism of action .
So we have the three publications already published and there's a fourth coming out on the mechanism of action , and I think when you can marry the mechanism of action with the activity , it gives you a lot of confidence that the drug is going to be effective .
Yeah , so how does that confidence equate to something valuable and tangible as a business , given that you know to the point that you just made and I can I can certainly validate that based on conversations that I've had with hundreds of of biotech founders given that mechanism of action hasn't historically been like a super important thing to understand , you know , as
long as there are safety and efficacy , right , like it's sort of been tertiary to the equation , right . So , given that historic , I guess , record , open that up for us a little bit , why is it advantageous to pursue that curiosity and fully understand the MOA ?
I think so . If you're in a biotech , you usually get one shot on goal , maybe two , and so you have to be very we're about failing , and failing quickly . That's our job , right , but you want to give yourself the best chance of success .
If you understand your MOA , it allows you to marry your mechanism of action to your disease that you're going to treat and you try to pair those up as much as possible .
So whatever activity the drug has and you look at the disease and you look at what's causing that disease or how to ameliorate the effect of that disease , then if you can marry those two , I think it's very helpful .
I think from the founding of a company building the team around a molecule where you understand the mechanism of action , it gives you a certain level of confidence .
And then I think the third thing , and probably equally important , is that when you're raising money , having that , if you don't have any human data or you're just starting out pre-ind , having that mechanism of action and the animal models , it builds confidence with potential investors as well that you are , that you will succeed or potentially could succeed .
It's not guaranteed sure , yeah , yeah , no guarantees . What ? Um , when , when dr dana first reached out to you and said , hey , would you be interested in in putting a company together around this ?
And you obviously did your due diligence and looked at the , that MOA and the and the molecule itself , what was what was sort of step one on on Clark Atwell's mind in terms of , okay , if we're going to put a business together around this , this is what we need to do imminently .
I think , a couple of things . The first one was trying to figure out what disease we wanted to go after and thinking the potential applications . That was one .
The second one was we were pre-IND , so the HGF itself at the time was we were using research-grade HGF from research suppliers that had HGF , and in order to move as quickly as possible into the clinic , we needed a source , and so we found a partner in Japan called Kringle Pharma , and they had been developing HGF in several systemic indications and so they had
GMP drug and they also had a package of data that was both clinical and preclinical . So that allowed us to leapfrog .
So that , combined with some idea of where we wanted to go with the molecule , we could build a business plan around that , where we weren't funding a company where we're going to have to go out and manufacture the drug and we were starting from the beginning line . We already had some momentum behind us with all of those things .
So that allowed us to go to several VCs and say , look , you know , we can be in the clinic in less than a year , and that was something that I think was attractive to the team but was also attractive to the VCs the team but was also attractive to the VCs and it allowed you to get a different kind of venture capital group behind you because they could see
that you could get into the clinic very quickly . So getting the drug , we had to have a license with our partners in Japan and they were fun to work with , because doing partnerships in Japan is notoriously difficult , but our partners are . They're biotech so they think like us , so they move very , very quickly .
And that was nice because we got to learn how we would behave as partners together and we were very happy that they were like-minded . And I think the next thing was we had to . So we reached out to Novo and I had a previous relationship with Novo through Lux Biosciences and Thomas Derberg and reached out to him and he liked .
He liked the concept very much , but we wanted to see if we could recapitulate everything that had been done at Harvard at at scale . And so Ken Harrison's , our partner from Novo , and he had recommended or suggested using OxyVator NGF as a predicate molecule . We had not decided to go into NK yet , but we redid everything that was done at Harvard .
We took those models and transferred them to a CRO and had them redo those models at scale . So instead of the three animals that they'll use in an academic lab , we were using 10 animals per group and we looked at different concentrations of the drug .
We used our GMP drug from our partner and we looked at comparing it to NGF , which is the active ingredient in OxyVein's drug . And at Harvard , ray and Sumil had done various different models .
They'd done a mechanical injury , a bacterial or chemical injury model and they had looked at prevention of scarring , they'd looked at acceleration of healing and they'd looked at regressing preformed scars .
And so we did all of that work at a CRO in North Carolina , howard Research , and we had set up with Novo preset success criteria and we exceeded those , and so that was when we closed our Series A .
Yeah , If you look at the sort of accelerated you know early timeline that you recognize that you would be able to take advantage of , Can you even begin to quantify how big a head start , in terms of I don't know years or even dollars , you might have had as you came into this engagement ?
I think the partnership with the work that Reza and Sunil had done and the partnership with Kringle probably cut three to four years off of our timeline .
Yeah , it's incredible . Yeah , good starting position .
Yeah , so you mentioned you know you had to determine what you were going to put a stake in the ground in around your lead candidate and you've got a molecule that is showing a whole lot of positive data in any number of indications Trauma , you know other diseases that cause scarring , and how do you decide it's an advantageous position to be in ? Right Boy ?
We could probably affect quite a few conditions with this molecule . What goes into that decision-making ?
process with the investors , a lot of conversations with the team , a lot of consultation with Reza and Sunil and outside key opinion leaders , and we did have , initially , another indication that we were thinking about .
And as we were going through it and having these discussions it became very apparent from our scientific advisory board they're like guys , there's a much better disease for this drug and that was when neurotrophic keratitis sort of came into it . So it marries , you have an active wound , so we have the ability to accelerate wound healing .
It is a disease where the nerves are impacted and damaged . We actually regrow nerves . The nerves are impacted and damaged . We actually regrow nerves . And then it does have a scarring component in that a lot of the patients when they develop an ulcer , the stroma is impacted and when you impact the stroma you are going to get a scar .
So it sort of fit a lot of . We sort of think of HGF as a Swiss army knife and it was using the spoon , the saw , the pliers . It used a lot of the attributes of the drug . So it's something that we thought as an initial indication it would be a good way to go forward .
Yeah , yeah , it's a great analogy . I love an analogy that really helps a simple-minded guy like me visualize what's going on ? there . You mentioned just a few minutes ago that the data that had been put together from the early days you knew would make Claris more attractive to .
I think the words you used were a different kind of VC , so I want to understand that a little bit better the funding , the funding scene in general and your , your strategy around funding the company . But what do you mean by a different kind or a different group of VCs ?
I think if you think of VCs as an ecosystem , you have the mice and then you have the elephants and the larger VCs . They move together .
So they're always investing together and the reason for that is they like to write big checks or they have to write big checks right , and the reason for that is they like to write big checks or they have to write big checks , right .
So if you have a large fund , you have to , you have to spend your time on larger investments and then you only invest with people who are like minded that write those large checks . Because you can't have , you obviously can't deal with a smaller VC that can't write those checks right . Eventually they can't write the $20 million , $30 million checks .
So I think when you get closer to the clinic , as a function of the amount of money you need to raise and what you're going to spend , those VCs will come in . So I think in the early days you tend to attract smaller VCs .
But those VCs that are going to help you with an IPO or launch a product , or maybe eventually you might be sold to a larger pharma , but those VCs are going to want to write the bigger checks . So the closer you're to the clinic or in the clinic . That's where they tend to invest . Novo is a little different .
They do seed all the way through and they're different in many ways , a little different . They do seed all the way through and they're they're different in many ways . Um , they're also an evergreen fund , so they don't , um , they don't have limited partners , and so they um , they're a lot more patient , uh , and can be more patient .
So yeah , um , so tell me about that . I guess the those days for you , clark , um , I mean , you got Novo's , you got , you got Novo on board early . Were there other fundraising partners , players , other efforts on your part , or was it sort of like we got our big partner ? Let's move forward ?
Oh no , no , we talked to a lot of people . You talk to a lot of people and I think in raising money , the first thing is you have to be prepared with your plan and ready to go , because if you're out there for too long , that becomes a reason not to invest , right ?
If you've been raising money for a year and nobody's moving , that becomes that hurts you . So I think you have to have everything ready to go .
So we had our key opinion leaders ready to go , our SAB , we had our plan , we had our deck together , we'd already talked to Kringle , we'd spent a lot of time getting everything ready and then we went out the door .
We were fortunate that Novo came in early , but we had been talking to a lot of other groups , such as RA , who also invested in us , and we were also fortunate because it's a Harvard technology of having well , at the time they were called were they called ? I'm forgetting the name now , but they're Mass General .
They came in as investors as well , and so we were very fortunate to have them because they obviously understood that ecosystem , especially in Boston , so they were able to introduce us to a lot of investors as well . But no , we talked to a lot of people .
Yeah , yeah , was that like 90% of your job at the time ?
Yes .
Raising money .
That was the biggest part of the job . Yes , raising money was that , was that was that was the biggest part of the job , and it's it's a , it's , it's an , it's a necessary evil . I don't enjoy it . It's not fun , it is .
It is , however , really , really valuable if , in lots of different ways , one is you , your , your , your business plan is pressure tested and it's tested by very smart people . And there are people who are wanting to say no . Every VC that you talk to , their first thought is how do I just get rid of this ?
And if they can't come up with a reason , then they start to get interested and they move forward . But we learned a lot from talking to VCs . They pressure tested and fortunately , our plan was pretty good , but they did give us ideas . Every meeting we would get something new or think of something new . There'd be a question .
It was like how do we answer that ? So that was very , very helpful . I think through the process of talking to VCs and how they do their diligence , you learn a lot , and so all of our investors were very , very thorough in their diligence and we enjoyed the diligence .
It was rigorous , but you also learned that they're very smart people , and they're people who you want on your side more than just the money , but you want the thoughtful conversations and then the value they added during the process . So I think that's very , very helpful . And then there's some that you , you walk out of the meeting room .
It's like I really don't want their money . They're not nice people and they don't treat each other well Like you can watch how they treat their partners . It's like this is the people they work with . I don't want to work with how they treat people . So it's very , it's very , it's very it's . It's a necessary evil , but it could be very valuable .
Yeah , you mentioned that . You know , you said it's hard work and you said you don't enjoy it . You know which I can totally relate with . I'm like the furthest thing from a business development person , like sales , not my gig , Um .
But how do you , how did you personally , uh learn it and , even more importantly , reconcile uh with yourself , Like that that this is something that you need to do and that you're going to go out there and you're going to do it right , Like you've got to get comfortable with it , Despite your aversions , you , you've got to , you've got to embrace it and you've
got to go out there , Otherwise you'll drive yourself mad , Right ? So I guess , personally , what did you do to reconcile it ? And then , you know , you said you , you learned with every meeting and improved with every meeting , but even even in advance of that , going into it , like how , how did you learn how to be a fundraiser ?
Well , I think I was . So my education started at at iTech and I . It was my first time at a company where I was a consultant , but I had a lot of interactions with their board and so I saw how investors their investors ask questions , what they were concerned about , what they were interested in .
So I think that was my first sort of touch , I think at Lux . I was one of the co-founders of Lux and Dr Uli Grau was our CEO and I watched as he approached the fundraising . So I was with him through that process , so I was kind of co-pilot , as it were , in that process as a COO and so I followed that COO and so I followed that .
And then I was very fortunate that at that time I had Thomas Derberg was on our board at Lux and he very much became a mentor to me and I learned a lot from his , from conversations through him , how an investor thought and what was important to them .
I think the fact that I don't like the process it helps you select better projects , because you're like I'm going to go out and I'm going to have to for the want of a better word drink from the fire hose and I'm not going to enjoy it , so it better be worth it .
At the other side of this , I think you pick projects that you you think will , uh , really work and that you're excited about , and so I think that it kind of it's a good litmus test for for a good project .
It's like , oh , this is gonna suck and I'm gonna have to go raise this money , but I really believe in this and I really want to take this forward , so it's awful that way .
Yeah , and I imagine that would hold some weight . Like you sit down in a meeting and if you know , if you're fortunate enough to be in a meeting with a VC group who is tuned in to your personality and what you're doing there , like why you're there , I imagine that has got to hold some some weight with them .
Versus , you know , versus the , the biotech BD person , or fundraiser , um , who enjoys the sport of it , right , like you don't enjoy , you don't you know ? I almost feel like going into one of these meetings and being like listen , guys , I'm not here for the sport of it is probably going to set you off on the right foot from the outset .
I think it does . I think we're fortunate that we have our investors are amazing . I enjoy working with them . They're thoughtful . I learn things from them . They guide us well .
Our board meeting we take votes at board meetings because you have to for meeting minutes and things like that , but we've never had to take a board vote for anything at Clara so far where it's been contentious or people have to vote . They're very , very smart people and super supportive .
I mean , if you think about when Silicon Valley Bank blew up and all of our money was there , we got calls from . It's like we have money . If you need to make payroll , we're here . They were calling us on the weekends and just incredibly thoughtful and , um , yeah , just good people . Yeah , a lot of a lot of entrepreneurs have bad stories with vcs .
I I don't have any really yeah but I think it's partly that selection process yeah , you You've mentioned you've used the word we like in those early days building the company fundraising . I want to get as sort of an abbreviated chronology of the we from the outset , right .
So like it was you and these two doctors from Harvard , some other folks who were interested , you got some VCs on board , started building a board . What did the we look like then ? The we of ClarisBio , and kind of walk us through what the we looks like now as you're in the throes of clinical activity .
So we started out it was Ray Z Raisa and Sunil and myself initially , and then Meredith Fisher at Mass General was very helpful and supportive of us and helping sort of we would bounce ideas off of her and she's still on our board and an amazing person and super thoughtful . But that was the we at that time .
And then , as we moved forward , we had a legal team and so Joe Favors is our counsel and again , I've worked with him for 15 years . He's an amazingly smart person and very thoughtful . But we worked with them . And then , after the legal team , our first hire was Dr Susan Orr . She had done diligence for Alcon on Lux Biosciences .
So I got to know her through that process and we just stayed in contact with each other and had great respect for her because she was doing diligence on the questions and the thoughtfulness and the integrity was very important . So Susan came on board Shortly after that .
Piotr Braila came on as our formulation CMC expert and it was funny we had mentioned to the VCs that we would , or to our investors that we would formulate the drug in four months and they were told this all it was funny we had mentioned to the VCs that we would , or to our investors that we would formulate the drug in four months , and they were told this
all it was impossible , and he did it in four months , so it was very good .
We were lucky , though , we have a good protein that's very stable , and then from there it was during the pandemic , so we were all co-located in different places , and so Susan had worked with Tom Nidalan , who was a clinical expert in development , so we brought her on and then so we were a four-person company for a while , and then , about a year , year and a
half ago , we decided to bring on somebody who would be our chief business officer , and we were very fortunate to that was through a recruiter and met Henry Routh , and he's joined , and we're very lucky . We get along very , very well . We finish each other's sentences . I am a recovering micromanager , so I'm on the I think , step 11 .
And so I think that's really helpful for me that we've been a virtual company for the last couple of years , so we don't have tons of meetings and everybody's very , very good at what they do and very senior , so we don't monkey with each other's work a lot and they have a really good culture , very like-minded people .
So that's very important because I think one of the things I've learned as a CEO is culture eats strategy for lunch . And if you don't have the right culture , it doesn't matter how brilliant your strategy is . Yeah .
Yeah , yeah , yeah . That's selectivity , again selectivity . You mentioned sort of selectivity being a theme around the VC exercise and I imagine that comes to bear pretty heavily as well when you're building out your , your C-suite .
Definitely , definitely . And again , I think it's that network and the people . You know I've I've been into companies with Piotr it's my first company with Susan , but I've known her for a very , very long time . And then our founders .
You know our scientific co-founders , you know Ray's and Sun , this dramatic allusion , you know , to changes in the standard of care and ophthalmic indications .
How important was it to you from the outset that you were looking at the potential for sort of changing the administration paradigm for potentially any number of you know ocular indications away from perinatal administration to topical administration ? Was that like an important consideration for you or was is that just like , oh man , this is really .
It's a , it's a nice to have .
So I think from from an administration . It was funny because when I was at iTech , Dr Chambers had told Dr Chambers at the time was in charge of the FDA and then ophthalmology and he had said that you shouldn't really go into the human eye with a needle more than four times in a person's life .
And so David Geyer definitely changed that paradigm and people go in every other month to get an injection for any VEGF or any of those therapies for AMD or DME .
But for us the sort of switch in the paradigm is that if you think about it , you still hear it from companies today that they're only interested in the back of the eye and the reason they say that it's code . For that's where the value is right , because you can charge to preserve and actually improve vision at the back of the eye .
You can charge a significant amount of money for that therapy and that also sort of wrapped up in the intended fact that they're biologics In the front of the eye .
The business model has always been volume , so the most successful drugs in the front of the eye are usually , you know , dry eye has been where you see the billion-dollar molecules and that's what's driven that , I think , with the launch of Oxervate , which is NGF for an orphan disease , that paradigm has shifted from proteins in the back of the eye to proteins in
the front of the eye and people see value there and they're also , I think , recognizing that there are a lot of other indications in the front of the eye that have been underserved . So usually the front of the eye is antihistamines , steroids , dry eye .
You know cyclosporine for the front of the eye and I think bringing biologics to the front of the eye is very exciting and we see several indications that we're very interested in . That we think would really help patients .
Yeah , you mentioned Oxervate and we talked about this the last time we spoke , so I'm hoping we can spend a little bit of time talking about drawing some , you know , sort of contrasting what you're working on versus the approach there Is . That is the approach there .
Oxervate is used to treat NK correct .
That's its indication and it's the first biologic to be approved for use in a topical front of the eye condition ? Would that be considered the standard of care right now ?
I think it's rapidly growing to become the standard of care . I think if you think about the treatment of patients with NK , the first stage is always to look at are you treating that patient with any other topical drug or even systemic drug that could damage the front of the eye , so a typical drug with a preservative in it ?
You definitely take a patient off of that . Then you move into therapies that are not proven in large clinical trials . So you could do serum , you could do platelet-derived factors you could look at . Insulin is sometimes used .
And then you go to the sort of more surgical like a tessera fee , where you sew a portion of the eye closed so that the lid covers the wound and protects it and hopefully helps heal it . And then the other thing is amniotic membrane , so you can put an amniotic membrane on the surface of the eye .
So those are sort of the gamish of things that were used prior and I think OxyVeid , because of its efficacy , has come to be the standard of care in neurotrophic keratitis .
Yeah , efficacy . However , the I guess DIY formulation of the therapy struck me the last time we spoke . Maybe it didn't strike me as much as what you just mentioned sewing part of the eyelid shut to cover the wound . That sounds sort of barbarian . Maybe effective , I don't know , but it sounds like we could move away from that if science allows .
It sounds like we could move away from that if science allows . But in the case of Oxervate , I believe you told me it was like a multi , like in the teens step process for the patient to self-administer this drug and that just sounded untenable to me , particularly in a patient population that is largely elderly , I would assume .
Correct . Yes , the average age of the patient in neurotrophic keratitis is roughly around 65 years of age , and I think so we were blessed with a very stable molecule . Ngf is neurotrophic growth factor , which is the active ingredient in oxirvate is relatively unstable and so the drug has to be formulated by the patient , and that has a .
It's inconvenient for the patient , it's inconvenient for the prescriber , because they have to teach the patient or their caregiver how to formulate the drug and then from there it also limits the use of the drug .
So we've had conversations in our market research where physicians have said if my patient's not an A-type personality , or they're not their caregiver's not an A-type personality , I won't even prescribe the drug , because I know that they won't follow through with the compounding of the drug on a daily basis . So I think that's an important differentiator for us .
We have our drugs delivered in single-use containers and preservative-free , and right now we know that we will be able to deliver it to the patient refrigerated , but then from there the patient has three months at room temperature in which they can use the drug , so there will be no formulation .
That's important because it's convenient for the patient , but I think it will also expand the number of patients who can use the drug . And then I think the other aspect of the drug that we're very excited about our drug is that it seems to be very safe .
We obviously don't know the absolute data from our trial because we're masked so we don't know who's on drug and vehicle . But if we look at the overall side effect profile , we're seeing that profile is very consistent with the vehicle arm in the Dompe study . So we're very happy . It's a great safety profile and I think that's very , very helpful .
Ngf itself is a pro-inflammatory molecule and so the patients do exhibit pain upon installation and so we don't see that . So I think that's going to be another benefit . But I think the coolest thing about our drug is we do see that Swiss Army knife .
So I think if we see , we not only see a potential for the treatment of neurotrophic keratitis and the resolution of the wound , which is the primary endpoint , but there may be other aspects of the drug where we see reductions in scarring which would end up in improvements in vision for the patients .
We may also see improvement in sensation with the drug because we do grow nerves . So there's a lot of reason to believe we bring more to the patients with this disease and then other diseases as well .
Yeah , yeah , I mean , it all sounds like upside .
We have to prove it though . We have to prove it Right , right .
Yeah , you got to prove it . You got to . Yeah , of course , as far as proving it goes , I mean , if you prognosticate for a moment on , you know , I mean part of your job is to obviate , to see what could be coming around the bend to thwart your progress that perhaps you know was unexpected .
I think that's what obviate meansba , means right , expect , somehow foreseeing the , the unexpected and being ready to deal with it . Maybe loose definition , um , what , what do you ? I mean , can you , can you pinpoint anything that that could stand in the way ? Like that you're that , you're concerned about I .
I wake up every night thinking about these things . I'm sorry , I'm sorry , no , no , no , no , no , it's , it's , it's , it's , it's the other part of the job . I , I think . For me , I think , the the being being we're second to this disease , we rely on what's gone before us for powering the trials , and so we're conservative people .
So we've chosen the vehicle arm . In the two trials that Oxervate did , that did the best . So they saw complete healing at week eight at roughly 30% in the vehicle arm . So we're using that as our baseline in the best . So they saw complete healing at week eight at roughly 30% in the vehicle arm . So we're using that as our baseline in the trial .
So if that's different , in their second trial it was around 19% . So if it's different but it could be different in 40% , you know , we could see 40% healing . That's a concern . So that to me is the major concern . I think I believe our drug will work . From the animal studies , from the work that's been done before , I think it will work .
It's an endogenous protein that we make to perform this function in other parts of our body and the eye as well . It's produced in the eye . It's produced in the eye , it's produced in the lacrimal glands , it's produced in the cornea , and so it's there . It's there for a reason . We're just providing more of it . So it should work .
But for me that's the main concern what our vehicle arm is going to do . Vehicle arm is going to do .
So , speaking of the production of HGF , how is it produced and manufactured ? At Kringle , I'm assuming .
Yes , so our partner in Japan , kringle , manufactures the drug . They use Chocell's traditional biological manufacturing and together we're developing a new process at Catalan to scale to a much larger yield than currently Kringle has and that process is going very well .
So we're very happy and we'll be introducing that API from that in a further as we move forward into the clinic .
Yeah , the effort at Catalan does also show cell Correct .
It's using their GPEX lightning show cell and it's a much more modern process and a more advanced cell .
So as far as clinical supply right now , you're content with your clinical supply right now . But that move is it to advance into broader clinical studies or is it anticipation of serving a larger patient population ? What sort of precipitated the need to turn to Catalan and look at scaling that up ?
I think several things . One is we're advancing to commercialization . So I think , looking at that perspective from a commercial perspective and having a more robust process I think the process that Kringle has is very robust . When we get the certificates of the COAs from Kringle and we test the drug as we have to , it always hits the numbers right on the spot .
The Japanese manufacturers of drugs do a very , very good job , so there's never been a question of that . But I think as we move into commercial , we're going to need more drug and it's always good to have two sources . So those are the two main reasons .
Yeah , yeah , okay . So give us a clinical update when are we right now in terms of clinical activity and then maybe not to bait you into a forward-looking statement , but what might be coming next in terms of clinical activity for CLARIS ?
So we have completely enrolled our current trial and we will have a readout in the latter part of July . So that's very exciting , nerve-wracking but exciting at the same time . And then from there we have initiated two open label trials . One is in a reversal of scar .
So in the animal work we were excited by the ability to look at preformed scars and see if we can reverse them . And we've been able to show that in two animal models that I've mentioned . And so we're very excited to see if we can do that in the human model , as it were .
And so we've enrolled five patients to date in open-label trials and we're seeing some interesting effects . So we're very , very happy with that . That would be a completely new indication .
There's currently no therapy approved for the reversal of scars , and so that would be it's terra incognita from a regulatory perspective , so that'll be , but it's a great area to actually go in and remove scars from people that have that in their central vision . I think it would be a huge benefit .
Yeah , just curious , just to stay there real quick before we move on to the other indication . When you talk about the reversal of scar tissue , healing scar tissue , you know , does that open up like am I thinking of this correctly or too simply ?
Like that opens up an entire , like it could be I'm not sure how to phrase the question Like scarring can be caused by any manner of things right , disease , infection , trauma . So are all those on the table when we talk about scarring ?
Almost all of them . I think initially we're looking at the initial patients , that we're looking at largely microbial keratitis or microbial infection , but we will include viral and we will include I think we have already included one mechanical injury patient as well .
So I think , yeah , you're absolutely right , all of those things on the table , we would be successful in all of them . I don't know , but we're going to look at as many as we can . And the other indication is limbal stem cell deficiency . We have enrolled in our trial , in our neurotrophic keratitis trial .
About 20% of our patients have limbal stem cell deficiency and we've seen some . Obviously we don't know if they're on drug or vehicle , but for somebody to have an improvement in that area is rare , and so we're starting to see that as well in some of our patients , and so that's given us the impetus to move forward and look at that as a separate disease .
So we'll begin enrolling patients this week actually who have that lymphocytes cell deficiency , and that's a brand new indication that we're very , very excited about , because there is no pharmaceutical treatment for those patients . Most patients actually have to be treated with a transplant , a stem cell transplant , the current therapy .
Yeah , that's pretty fascinating work . What haven't I asked you , Clark that is central to the story that I should have asked you if I were better at my job .
I think you've done an incredible job of asking really , really good questions and I thank you for that . I appreciate that , yeah .
What's next for you ? I mean , like I mentioned from the outset , you've been plugged into this space for going on 20 years . There's a lot of work to be done at Claris . I'm not going to ask you to tell us where you're going next , but I'm assuming you're going to plug in at Claris and remain committed to the task for now .
But any imminent plans for what Clark does next , whether at Claris , or otherwise .
I think for me right now , claris is everything and we're very much focused on the next stage . So we're preparing for the next trials and we've manufactured drug for that . We've been fortunate enough to speak to a lot of interested venture groups that would join our Series B and we're planning to move the company forward into an IPO .
So I think that all of those things are main focused , I think , for me personally . I think the joy of being in this space is that if you do a good job , um and and by that I don't mean necessarily if you were the drug doesn't always work .
Sometimes it does and sometimes it doesn't , but as long as you gave it the best chance and you , you get a result that everybody can sit around and say , yeah , this is the truth . What we found is the truth that I think you're fortunate enough to do it again and again and you get that opportunity .
So yeah Well , very good , I uh I appreciate the time that you've spent with us . Very thoughtful conversation , uh , our initial conversation was so . That's what inspired me to want to have you on the on the podcast .
I just enjoy the uh , the transparency , the humility , uh behind your approach and your personality and I I'm glad you came on to spend some time with us , clark .
Oh , thank you . Thank you very much , I appreciate it .
We'll do it again . We'll you know . You've got you've got a readout coming up in July . You got a lot of exciting stuff coming down down the pike , so we'll stay in touch and we'll have you back on when there's , when there's more to report on . Thank you very much . I look forward to that . All right , so that's Claris Bio founding CEO , Clarke Atwell .
I'm Matt Pillar . You just listened to the Business of Biotech . Listen and subscribe wherever you listen to podcasts . Sign up for our Business of Biotech newsletter at bioprocessonlinecom . Backslash . B-o-b . Drop us a line with your guest and topical suggestions . Be sure to get in touch and let us know which episodes you're picking and which you're panning .
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