[00:00:16] Speaker A: Welcome to the Few and Far between podcast. I'm your host, Chris o'. Brien. Quick question. Are you a doer or a thinker? Each role has its advantages, of course, but what if there were another option? My guest today defines himself as a builder, creating successful companies and teams as well as innovative therapeutics. Woody Bryan is the president and CEO of Revolo Biotherapeutics, a biotech developing revolutionary therapies powered to reset the immune system and achieve superior long term remission in autoimmune and allergic diseases.
On today's episode, we'll start with the story of Woody's journey across biopharma and emerging biotech and how that experience formed his methodology of prioritizing good science and good teams. From there, we'll go behind the scenes at Revolo and spotlight their current pipeline. The importance of a feather touch in fighting infection, plus how to optimize both drug delivery and patient safety. This episode with Woody is packed with information and insights from a veteran CEO that will benefit any biopharma leader. I can't wait for you to hear it. Okay, let's start the podcast.
Woody. Brian, welcome to Few and Far Between.
[00:01:29] Speaker B: Thanks, Chris. Thanks for having me join today.
[00:01:31] Speaker A: It's a pleasure. I've been looking forward to this conversation in part because many, many of the people who listen to the pod either have started biotech companies or aspire to doing that. And you've had a varied career, you've worked in different kinds of places. Big pharma, emerging biotech. You tell us a little bit about what early experiences shaped the way you manage and think about business today.
[00:01:50] Speaker B: Yeah, I started out of graduate school. I started in big Pharma and actually had a number of different company sizes and types that I had employment opportunities with. But I went to a large pharmaceutical company sharing plow the advice of my graduate school advisor. He's like, listen. He said getting an idea of how a fully integrated pharma company works is a wonderful first sort of experience. And sharing was fantastic. But I found out that it was just, it felt a little too big for me, you know, And I think that sort of goes to feeling like I was in a position. And of course I was, I was early in my career. But I felt like decision making was more by committee. By committee.
[00:02:31] Speaker A: Yeah, yeah, yeah, we'll meet to have a meeting about the meeting kind of thing.
[00:02:34] Speaker B: Yeah. So great organization, great, you know, great culture. Just I felt like I wanted to be closer to decision making and more time moving the ball, if you will, on projects and various things. Than the infrastructure around it, if you will.
[00:02:50] Speaker A: Will you size the company a little bit for us? So Shearing I suppose would look small today compared to megapharma players, but give us a sense of like, you know, if somebody's considering that and they think that sounds like really good advice, how big of a company are they looking at where you think they can get a sense of an end to end ish experience?
[00:03:08] Speaker B: Well, I think the industry, the layout now and the in the roster if you will, of companies is quite different. But at the time Shearing was like a top 10 pharma company. Of course they're merged with Merck now. I think there were 25,000 employees and mind you today, I don't know, I guess the top one or two probably have 100,000 plus employees. So that gives you a scale. But at that time I think they were far less what I would call somewhat fully integrated sort of mid cap biotechs, I think a big cap biotech today that has sort of research development, you know, clinical development and many of them now have their own commercial team is a good place to learn, you know, and there are some of those, many of those are public. I would say that, you know, anytime you add in a commercial salesforce, even if it's a specialist call point, you add in marketing, you add in support, you add in reps, you add in district managers, regional directors, you've got probably at a minimum 100 plus on the commercial side and then you've got everything else. So you're talking probably minimum three to 500 employees to get it. But the point is within the organization they first of all they have the financial wherewithal and the critical mass to do all stages of development. So you get to see sort of the, the integrated look at how things work within a company.
[00:04:24] Speaker A: That makes a lot of sense. So you take those lessons and do you immediately start going to, you know, startups and early stage stuff or is there an interim step?
[00:04:32] Speaker B: Yeah, I had an interim step. I actually went into the pharmaceutical services sector from Sharing, which is kind of the other end of the spectrum. Went to a company called AI. I went there to actually lead a, develop a formulation development team because my background is in pharmaceutical drug delivery. I knew the guy that was head of R and D from the past and had great respect for him. So I went there. Company was private, you know, doing subcontract formulation development, manufacturing and analytical services.
And then we had proprietary technologies and that was my sort of sweet spot. So went there. It was an interesting challenge because they wanted to grow, which we ultimately grew, the business. And that was my first taste of being part of a team that took a company public.
[00:05:14] Speaker A: Okay.
[00:05:14] Speaker B: And then I made the transition a year or two after I arrived into the business side. And again, that was a pretty drastic change, I bet. Yeah, job wise. And again, it was fast moving. I mean, we had several hundred employees, but we were still nimble enough to make those sort of changes and not have to go through a long process. It was great. It was one. It was a game changer for me from a career standpoint.
[00:05:39] Speaker A: So let's unpack that a little bit. So did you struggle over the decision to make that move? I mean, you had spent a bunch of time training as a scientist, et cetera. Like, what was that? Or was it like, no, no, no, put me in the game. I really want to get into the business side.
[00:05:51] Speaker B: Well, it was by happenstance that I got the opportunity. I went to a retirement party. We had a gentleman that was retir on a Friday afternoon. We had a happy hour get together to send him off. And while I was there, the guy that was running essentially the sales business development side of the business was there, and I knew him within the business. And there had been another gentleman in the organization that had held a position, what we call then a technical director. It was really a technically trained person who was out pitching our story, our services, our platforms to everybody from Pfizer to startup biotechs. And that gentleman had left the organization. I knew him, I had worked with him. And I just opened my mouth and told the head of sales, I said, that's a cool job. I really wasn't. I didn't know I was pitching for his job at the time. And we had a conversation around it, and I did a lot of presenting. Anyway, when once we sort of started advancing discussions with the pharma, and this guy that had left was sort of the front end of identifying those opportunities. So that was a Friday. I received a call on Monday from the head of sales and the CEO and they said, we have a proposal for you. I said, oh, okay. They offered me the job. And what made it easy was rel, you know, easier is as they said, listen, we want you to take the job, try it for six months. If it's not to your liking, you know, you'll go back to leading the formulation team that you're currently leading. And I never look back. It was a wonderful balance of seeing the bigger picture, understanding the business aspects of a deal. Obviously, the technical part I knew and Also being able to be out in what became a vast network of talking with executives from small companies, large companies.
[00:07:38] Speaker A: Turns out you're good at it. But it was so it was really smart of them. They gave you basically like a risk free option to try it. Obviously they must have felt pretty good about it because you don't pull a person out of a role where they're effective, put them in one unless you think that they're going to be able to add more value for the organization. That's a clever way for them to have done it. And then off you go. So then you're a commercial guy or a business guy who is a double or triple threat because of the science and technical knowledge. Is that kind of how things go for a while?
[00:08:03] Speaker B: That's right. And then, you know, the neighboring sort of tasks that went with it, which I added on to my responsibility not too long after I took over the group that actually wrote the contracts. So I got into sort of the legalese of negotiating licensing deals and I'd done a lot of fee for service stuff. So I was familiar with contracts on just a fee basis, you know, negotiating those, looking at markets, running a contracts group and then. And I gradually had an expansion over the ensuing five or six years within the organization along those same lines. And then like I said, we were very successful in growing the business. The sales were something in the $20 million range and we grew it to somewhere close to a hundred million in about five or six years. And then we took the company public. And so yeah, that was fantastic. It was building a business within a business to a certain degree also.
[00:08:49] Speaker A: I'm sure it broadened your skills in a bunch of exciting ways. So you come out of that that was, I'm sure first of all a huge win. Must have been great for your self confidence, presumably good for your bank account. And then you're thinking about what comes next and is that when you make the pivot back into biotech or into pharma?
[00:09:05] Speaker B: It is, you know, so being in the service business it was wonderful. I mean, you know, I've never worked harder in my life. Well, I shouldn't say that I work very hard now. But it was a frantic pace because timelines never changed, even if the partner was slow in making their decision. And no two days were ever the. Which is kind of a theme around why I went on to seek out business building opportunities. So the next opportunity was Shire had actually begun their journey into the US market from the UK and had done so by acquiring two companies in the late 90s. One was FarmAveen in Maryland, Rockville, Maryland, that had a number of CNS related products that were technology enabled. So that was the sweet spot for me. And then they also bought Richwood, that had the Adderall franchise, adhd. And so those two kind of came together and what Shire wanted to do was to leverage the platforms and to partner with other companies because they were really focused on neurobehavioral. They said, hey, these technologies have a lot of bandwidth outside of that one therapeutic area. So I was hired to do that, to work for Jack Guitar. Jack was running Shire Labs, was what Pharmavene became. And again we built a partner facing business from. From zero.
[00:10:19] Speaker A: Yeah, so very entrepreneurial, Very entrepreneurial.
[00:10:21] Speaker B: And the cool thing was we had the backing of a big company, but we were also responsible for strategy of nominating pipeline candidates for Shire. So we had sort of a dual responsibility.
And so we were nominating product opportunities to Shire in the area of interest to them. And then we were partnering our platforms and doing development and partnership with external companies. And we ended up doing, I don't know, eight or 10 deals. About five or six of those went all the way through development and became commercial products. And we built a revenue stream. Shire changed. Their CEO Matt Emmons came in. Ross Stahl had been the prior CEO. Matt came in and Matt was a Merck guy. Nce guy really wanted to explode the organization and do more higher risk opportunities. And he was kind of at a loss as to what to do with us.
[00:11:13] Speaker A: You guys. Yeah, right.
[00:11:14] Speaker B: So we said, well, hold on, we're going to go raise money and buy this division from you, if you will. And we did. And so Jack, myself, Pat bott were the three management guys. We formed a syndicate from NEA, Abingworth and OrbiMed, raised a Series A of 45 million. And then we ultimately, what was really cool, the drug delivery deals we had done, we were able to monetize all of those through about three tranches. And we raised somewhere close to $200 million non dilutively to build a company.
[00:11:43] Speaker A: Wow, that's a crazy story. Yeah, that's a crazy story. So I want to pause and say two things. First, usually when somebody says, yeah, it's the best of both worlds, it's entrepreneurial, but we big company behind us, it's usually actually the worst of all worlds. You don't have a lot of resources and you have a lot of bureaucracy. So was that not the case or did you have to kind of carve your way through that, I gotta tell.
[00:12:03] Speaker B: You, Shire was incredible in that regard.
You know, Adderall was just, you know, the whole ADHD market didn't really even exist almost until they got into it. They were on the, on the Adderall side. You had J and J on the methylphenidate side and they were, they were duking it out. Right. But they really both developed the market and obviously a lot of capital coming in. The company was growing. Market cap was, you know, was skyrocketing. But they let us, you know, we really made some, some strategic decisions.
[00:12:34] Speaker A: That's really cool.
[00:12:35] Speaker B: We operated a lot more like a small company, entrepreneurial than a big bureaucratic one.
[00:12:40] Speaker A: Yeah, I mean, I think people talk about wanting to be able to make that happen inside of large organizations, but those are precious few things that come along.
[00:12:48] Speaker B: Foreign.
[00:12:56] Speaker A: Hi, this is Chris o', Brien, host of Few and Far Between Conversations from the Front Line of drug Development. We'll be right back with this episode in a moment. I personally want to thank you all for listening to our podcast. Now in our fifth season, it continues to be an amazing opportunity to speak with some of the top thought leaders in the drug development industry. If you're enjoying this episode, please leave us a review on Apple Podcasts. It really helps people discover the pod. And don't forget to subscribe to Few and Far between so that you never miss an episode. One last request, Know someone with a great story you'd like to hear me interview. Reach out to
[email protected]. thank you. And now back to the podcast.
Okay, so, so then you take that company public. Is that where that goes?
[00:13:41] Speaker B: Yes. The new company name was called Supernas, which is a highly successful publicly traded CNS commercial stage company. So I was running, you know, business development, sort of corporate development. I also had responsibility for organizing strategy with obviously a team.
So when we became Supernas, we took the drug delivery deals, which I mentioned that we ultimately monetized, and we had some assets we were developing for Shire that they had not officially taken into the broader corporate pipeline. So we were like, what do we do with these? We took those with us. And two of those epilepsy products, Trokendi and Oxtella XR became. We developed them through a 505 B2 path using our technologies. They both got approved. That was in 2005 when you started the company. So fast forward, they were both filed in like 2011.
They both got approved within nine months of each other. And we took the company public and built our Commercial sales force.
[00:14:36] Speaker A: Holy moly.
[00:14:37] Speaker B: Initially, I think we had 75 reps. Victor Vaughn, who is a legend from the Shire sales tree, actually he built Shire's U.S. sales organization.
He came over to join us and build out the commercial infrastructure. And off we went. And then later on, so it went public in 12. I stayed for another three years. I had in licensed a couple of other assets, one of which is Kelbry, which they got approved not too long ago. So a few years ago.
And it was essentially an older molecule that AZ had. I went to them and said, you're doing nothing with this. We're like mechanistically is on the shelf and had been. They sold me the data set and essentially it became a new chemical entity, although it had had some history.
And of course, we were developing it against modern standards and Admetox and of course clinical. And we developed a proprietary dosage form.
[00:15:31] Speaker A: So did you have to start over with a phase one or could you use the safety?
[00:15:34] Speaker B: And so the tox program was sort of abbreviated because we went to the FDA and said, here's what we have, here's what we know we don't have. Help us understand. So, but essentially it was a. It was a new chemical entity development program that had some data behind it, allowed us to do some things a little bit differently, but the stages were all the same.
[00:15:53] Speaker A: But you knew a lot more than people often know when they're in licensing, right?
[00:15:56] Speaker B: Yeah, yeah. This was on the other side. This was a complement. So you had all the stimulants, like I mentioned, Adderall, Vyvanse, methylphenidate, Concerta. And then at the time, Strattera had come in as the only non stimulant in adhd.
And it just didn't work very well. It was kind of a soft feather in a disease state that probably requires a little bit more potency, if you will. So Kelbir is that we saw an opportunity. Mechanistically. It had some similar mechanistic attributes, but also some differentiating ones. And it turned out it worked. And it's in the market today. Yeah.
[00:16:30] Speaker A: So, okay, there's a couple of themes I want to pull on there. One, when you brought those orphan assets with you guys when you started things, did you think, like, there's a high probability here these are going to become approved drugs? Or was it like, well, we might as well take them?
[00:16:42] Speaker B: Yeah, I think there was a mixed bag, you know, the two epilepsy ones. One was further along than the other, which was trochindi topiramate and it's a 505B2. So we were improving delivery and side effect profile by smoothing out the peaks and troughs. Oscar Bezepine I actually licensed that program out to another company. We did a phase one. We had a disagreement on what the data looked like and they said we're out. And I said well we're in, we'll take it. And we took it. It's been a very success. I mean I give credit to the team. There was a solubility limitation that you had to be sort of creative to understand how to fix. And our guys were really good at solubility enhancement along with control release and that was the key.
[00:17:23] Speaker A: So is this a fair up until. Up till now in your career, is this a fair statement? It feels to me like one way to think about, you know, a successful biotech career pharmacareer is to try to figure out how you can take risk out of the process. So if you can in license a drug where you know something about safety, profile of it, if you can take something that's partway through a stage where you feel like you've got a differentiating skill set, it seems like you did several versions of that versus just saying like hey, we've got a brand new. We're going to start from scratch.
[00:17:51] Speaker B: Yeah. I think if you put shearing plow aside for a moment and you sort of start with that progression being in the services side. Yeah, with our technologies at AI we were layering them on to nces but also a lot of known entities like lifecycle management stuff. So there was a mixed batch of risk profile there and we weren't the ones spending the money. Right. It was somebody else's money.
[00:18:10] Speaker A: Yeah, right, right. It's a great way to learn through.
[00:18:12] Speaker B: The technical expertise we had technologies and then if you go to Shire at that time, kind of like AI, but for Shire's purposes they were all 505B2. So we were new sort of delivery thought process around neuromolecules. So lower risk on the partnering side. Most of those were 505 B2s or at least they were molecules that had advanced into the clinic and had been de risked. And there was some rationale that came to light that said, you know, maybe, maybe there's nausea associated with C Max. Let's smooth it out and try to maintain the efficacy and the good aspects attributes.
And so it was a little bit of a step up in the risk taking risk category. And then later on and of course now I'm more in the NCE world, but it's been a little bit of a step up each time.
[00:18:59] Speaker A: You're supposed to become less of a cowboy when you get older.
[00:19:01] Speaker B: Come on, somebody didn't tell me.
[00:19:05] Speaker A: So let's talk about that. What made you make that switch? Because I think, look, you've obviously you were massively successful at figuring out where is there an underappreciated opportunity? I guess you could say where is there less risk than the market is perceiving or the owner is perceiving. So therefore we're able to buy it and do something successful with it and going from that to like, no, we're going to take a big swing at something hard and new.
[00:19:29] Speaker B: Yeah.
[00:19:29] Speaker A: Talk about that a little.
[00:19:31] Speaker B: Well, I think to talk about the next sort of stops helps answer that question. So, you know, I felt like I had been had a great run at Supernas. Jack was a terrific mentor at Shire and Supernas. The company was humming along. We had a full pipeline. And then I had an opportunity to help Lupin build a brand business. They had some legacy products and they were calling on pediatricians, but they didn't really. They're a big generic house. But they had aspirations to get, you know, deeper into the brand side. I knew the guy, Paul McGarty, who was the president there from my AAI days. And we went over and talk about risk. We were able to identify to asset that was de risk because it was NDA stage in the women's health arena. And Lupin ended up acquiring the company and launching the product. And that was sort of a different from a regulatory risk standpoint was higher than 505 B2s. But it was a step up even though it was late stage. And then on to Sucampo, where Sacampo was big enough and worked for Peter Greenleaf. Peter's on our board now, another great mentor. And. And they had a single asset that they partnered with Takeda, which was Ambatiza, a GI product. And Peter wanted to build out the pipeline and we did. And in the course of bringing in mainly new chemical entities, we were acquired along the way. So we sold the company. But it was the same sort of strategy of balancing risk by different levels of science, different stages of development to complement. We had a very nice cash flow coming in from Amitiza sales. So it allowed us to be somewhat competitive in, you know, in certain in licensing opportunities.
[00:21:10] Speaker A: So kind of as you're moving further here, you are taking more risk. It's still sort of thoughtful risk where you think you Understand some things and you think you have some advantage as you come at it.
[00:21:20] Speaker B: That's right.
[00:21:20] Speaker A: Okay, great.
[00:21:21] Speaker B: The unmet needs are fairly well defined. The asset has some data behind it. Yeah. And then, and then I went on to Urogen, did the same thing they had, you know, the kidney cancer product gel Mito that was in development, ultimately got approved again. Wanted to build a pipeline behind it and we were successful in bringing in a new chemical entity which they still have in development before I came to Revolo.
[00:21:44] Speaker A: So, okay, so that brings us to the current chapter or the beginning of the current chapter. So how did that happen? What was Revolo before you got involved?
[00:21:51] Speaker B: Yeah. So Revolo had the two assets we have under roof right now. Both came out of academic research institutions in the uk. We still maintain an R and D group in the uk. We have a lot of collaborators, advisors, even service providers. But it had largely been financed for a number of years by individuals, high net worth individuals. It was kind of a pre clinical research exercise almost as a carve out startup with only a few employees. And they said, listen, if we're really going to make a go of this and take these assets into the clinic and do something meaningful, we need to be in the US and so I was recruited. There's a guy that I had known for 20 something years, Jonathan Rigby, who was named, who's a Brit that lived in the States for most of his career. He called me one day and said, I've been named a CEO and I'd like for you to come join me and help me build a company. Because he knew I was a builder and I'd actually tried in past lives to buy a couple of the companies he started and got outbid each time. So I joined.
[00:22:50] Speaker A: Jonathan's a past guest on the podcast too. So we've had him on. He's terrific. Yeah, he's terrific.
[00:22:55] Speaker B: He's a longtime friend and will be forever.
[00:22:58] Speaker A: Gotcha. Okay. So he connects with you and you join.
[00:23:01] Speaker B: He said, let's do this.
And we did. We built the board, we built the team. Our team and our board today is kind of a mixed bag of people he knew and people I knew.
Yeah. So what was interesting to me was aside from the mechanistic novelty, we'll talk about 1104 because it's the more advanced. We've taken it from preclinical now to phase 2B ready and EOE. But there's a drug delivery element. It's an incredibly interesting peptide. And when people think peptide they go, oh, there are Delivery challenges? Well, well, we've demonstrated, in fact we had a press release last week that we are now accelerating our oral development program. So we're in a space that's dominated by monoclonals that are injected. Sure.
[00:23:43] Speaker A: Injectables. Yeah, yeah, yeah.
[00:23:45] Speaker B: Won't be oral. Older steroids that have safety concerns, JAK inhibitors that have black box warnings. There's a tremendous opportunity here. And so my background and my curiosity and fascination of different routes of delivery fit nicely and we've been able to generate some really incredible data.
[00:24:04] Speaker A: Was there a penny drop moment in the early days on this when you. Because as I understand it, part of what's exciting here is this is not immune suppression. Right. This is. We talk a little bit about the kind of core science.
[00:24:15] Speaker B: Yeah, sure. So, you know, if you look back in immunology in general, depending on what indications, and we're talking about Th2 diseases which is sort of IL4513 driven inflammation. You have atopic derm, asthma, EoE, chronic urticaria in that category. But if you look at the approaches that have had some success, a lot of those are cytokine specific targeted. So they shut down IL4, they shut down IL5 or 13. And those are cytokines that traffic or are attributable to certain inflammatory cell types, eosinophils, mast cells, what have you. So it's a downstream approach. So, so think of, think of there being a leak in the dam and an inflammatory cascade that is triggered by an allergen, a food alle or an error allergen. Once you start that cascade, what's out there today is sort of in a defensive mode like, oh God, it's out of control, let me shut it down. What they don't do is on the other side of the immune cascade is they don't do anything to increase activation of Tregs and B regs that are naturally in the immune system to react to and shut down inflammation before it gets out of control.
[00:25:25] Speaker A: Okay.
[00:25:26] Speaker B: So we work upstream, so it's like a road that bisects into the inflammation side and the regulatory side and we're high enough that we affect both. So they're downstream reactive inflammation impact only. Only certain cell types because they're narrow to certain cytokines targeted. We actually show an impact across an array of all of those cytokines. 4, 5 and 13, IL31 relative to itch and atopic derm. And on the regulatory side we see a very quick and persistent increase in activation of Tregs and B regs so the way we explain it is, first of all, all these cell types have. They do good things. That's why they're part of the system.
[00:26:06] Speaker A: Got them for a reason. Yeah.
[00:26:08] Speaker B: So what you don't want to do is use a sledgehammer and crush one or two to zero because that's when the good part goes away. And you're not. You can't fight infection. And that's, that's immunosuppression. We actually hit multiple levers on the inflammation and on the regulatory side with more of a feather approach.
And so it's a balance. It's like putting different sounds together to make a song instead of having a dominant single instrument, you know, and the.
[00:26:34] Speaker A: Goal is return to homeostasis. Is that.
[00:26:36] Speaker B: Yeah. So it's, it's basically trying to allow, if you will hit these levers to allow the immune system to work the way it's naturally designed to do so because it's lost some of that. And there's some retraining, right? I mean, there's phenotypic changes, there's some retraining of the signaling.
We change signaling between the dendritic cells and undifferentiated T cells is one aspect of our mechanism. And if you look at the numbers, you know, we change eosinophils quite a bit, but it's not persistent for weeks on end, necessarily. In between dosing, we believe the immune response functions normally and then the Treg activation is only a few percent or few fold increase over normal activity.
But it is something that is the more active, powerful T Rex. Not all T Rex. So you see people in the car T space. If you see people in car T, you hear people talk about, oh, we increased T Rex population by seventy fold.
[00:27:32] Speaker A: Yeah, yeah, yeah.
[00:27:33] Speaker B: We don't think that's good.
[00:27:34] Speaker A: That's not a great answer. Yeah, no.
[00:27:36] Speaker B: What do T Rex do? They tamp down all these other cells that you need for normal immune function. And listen, you know, some people say, okay, but is what you're doing with the feather approach across multiple levers enough?
Well, we had quick translation in our phase two study into very meaningful impact. This is why we go significant on both the primary outcomes.
So one way to wrap that up is if you look at eoe, right? Dupixent's approved. It's a little bit broader than some of the other single cytokine modalities. But a lot of the anti IL5s who said, oh, yeah, we can crush eosinophils to zero. And that's one of the primary endpoints we're going to go after EoE, they fail because they crushed the eosinophils to nothing. They had almost zero impact on the patient reported outcome dsq. So it's pretty achieved.
[00:28:22] Speaker A: The objective did not hit the endpoint.
[00:28:24] Speaker B: They were too narrow.
[00:28:25] Speaker A: Yeah, got it.
[00:28:25] Speaker B: Check on one. Did not succeed on the second. And we did.
[00:28:29] Speaker A: Okay, so am I thinking about this right? Are you spoiled for choice in terms of opportunities you can go after? It feels like the application set is really broad. Is that true?
[00:28:38] Speaker B: Yeah. So I mentioned the type 2 category. So obviously there's EOE, there's huge unmet need. Dupixent is injected once or week. They weren't able to have success at every two week dosing. It's painful. A lot of people say a lot of people, a number of people have success and good efficacy with it. So it does some good things for certain patients.
But a lot of people don't want to take a biologic chronically. They don't inject themselves every week. It has more of a developing history of chronic use. You're starting to see some side effects come to bear that naturally come with something that you give more often.
And then there's steroids. You know, Ihelia is approved, but they were being used off label. It's only approved for 12 weeks of therapy. So there's a dire need for a better, safer, maybe more efficacious and certainly a more patient compliant oral dosage form there. Atopic derm, obviously a lot more players there, an even bigger market, although EOE is growing rapidly. But atopic derm basically has monoclonals, sub Q injection.
And if you look at things like Dupixent's done tremendously well from a sales standpoint. They're doing, I don't know, 9 billion a year in atopic derm. But they're doing that by capturing single digit patient share. They've got like four. Yeah, only 4 or 5% of treatable moderate to severe atopic derm patients are actually taking it whether they choose or whether they can afford it, whether they can get insurance coverage. There are others, like Ebglis is coming in and doing well. There's a number of monoclonals, but again they are all relegated to subcutaneous administration. And then the other side, you have JAK inhibitors, black box warnings.
Some people like to take them and take the risk. But again, if they had an oral alternative that had a good safety profile and efficacy to match, I think there's.
[00:30:25] Speaker A: Tremendous Opportunity there feels like a lot of upside.
[00:30:28] Speaker B: Yeah.
[00:30:28] Speaker A: Okay. So when you're thinking you're making this decision seems kind of obvious, but I think what you're saying is I look at unmet need, you know, we look at the competitive set, you know, we think about, about size and, and then we make decisions about where to focus. That's like I said, sounds obvious. But if we look at a lot of, look at the biotech industry broadly, it's clear that not everybody's doing that. There are some trials that people raise a lot of money and get into the clinic and run trials aiming at pretty small markets or narrow.
[00:30:56] Speaker B: Right.
[00:30:56] Speaker A: So how do you think about the discipline there?
Am I identifying a real problem or do you think it's not?
[00:31:02] Speaker B: Yeah, I think it's about who the team is and the science and of course investors. Right. And obviously raising money, you're building expectation on what you're going to go after. And certainly people are going for game changing, you know, gene editing and gene therapy and there were, you know, big swings to basically wipe out a disease state with a single treatment. What I like about what we're doing is these are chronic diseases, they're growing. There have been some good innovation there, but there's a, there's a broad recognition in immunology and our lead assets, obviously on the allergic disease side that there hasn't been a lot of target, new target, target validation in the past few years. You know, monoclonals have been around for a while. People are making longer acting and all that sort of stuff. But in the Jak inhibitors that preceded them and they've been around forever and there's still a lot of patients that are underserved. So there's a time now where there's definitely a recognition. Not just a recognition, but their data sets been generated show that there need to be more upstream mechanisms. So there's hunger for that. And of course, always these are markets that you don't have to get a huge percent of the market to be successful.
[00:32:08] Speaker A: Yeah, that's a, it's a nice feature. Yeah.
[00:32:10] Speaker B: And it's a really concentrated call point. Even atopic derm, you know, there's, you know, anytime you have 20 or 30,000 dermatologists or gastroenterologists, you probably have 5 to 10,000 of those that really drive the market. You know, they're thought leaders.
[00:32:25] Speaker A: Yeah, decision makers.
[00:32:26] Speaker B: They see more patients, they take on the more difficult, they're the early adopters that a lot of the people fought, follow their lead. So it's concentrated as opposed to some of the bigger markets that require more commercial money and ads and TV ads and all those sorts of things.
[00:32:42] Speaker A: In a way it's another trying to be thoughtful and clever about how to play this in an optimized way. You guys could be described as either a platform or a sequence of programs. How do you talk about it and why?
[00:32:54] Speaker B: Well, yeah, I think there's an opportunity here because we are engaging a novel receptor with our 1104 program and it's chaperone in biology. So by nature it does multiple things. There's an opportunity obviously to build on that. And we also have IP on neighboring peptides that came from the original discovery and then I think within that the multiple routes of delivery. Although we're leaning into sublingual, we have a subcutaneous formulation ready to go in the clinic, we have an IV that's in the clinic and subcute can still be in certain indications we think very competitive.
[00:33:29] Speaker A: Got it.
[00:33:30] Speaker B: We just have to pick and choose and be capitally efficient. So there are multiple levers to think about whether it's a platform that gives way to new programs or more importantly that gives you some real flexibility as far as franchise development, lifecycle management, expansion down the road. This new sort of announcement that we're going to lean into sublingual. There's actually a quote in our press release from our PI, Evan Della and because you now have something that's oral, you can think about the potential to be first line therapy in eoe.
[00:34:01] Speaker A: Yeah, yeah, yeah, right.
[00:34:02] Speaker B: So you're not sitting there alongside the other injectables because it's thus far we've had a great safety profile. No serious adverse events, no patient withdrawals. If you couple that with the novel mechanism and more patient preferred oral administration, there are a lot of potential upside things that could happen with the program.
[00:34:22] Speaker A: Yeah, that's very, very cool. All right. As we close the thing that we always like to do at the end of these things is ask for advice. So imagine you are a new biotech CEO.
It's a tough world out there, it's tough to raise money right now. There's a lot of uncertainty. What advice would you have for someone who's starting on that journey? A fresh faced young woody, if you will.
[00:34:44] Speaker B: Well, it's all about obviously you have to have good science that you got to do your diligence there. And assuming you are past that, it's about team. I mean I've been fortunate to work for a couple of really fantastic mentors. I'm a curious Sort. So asking them and watching them and asking them for advice and being humble and at the team level, you know, I tell everybody, although our team has experts in different areas, you got to be able to play in the sandbox together. You know, we got to row together. I mean, there's nowhere to hide in the small biotech company. And you need everybody doing their part. Somebody that comes in as a finger pointer or has some sort of political agenda, they shouldn't be there and they won't be there very long because they're just destructive. But people that like to put on multiple hats, that like to weigh in a team that is receptive and respectful of the team members having different, you know, points of view. I mean, you can be a regulatory person and be in a conversation about stabilizing a peptide.
And although as a regulatory person, you're not the CMC expert, you never know when the regulatory person is going to say, hey, you know, we had a similar issue at xyz. Let's think about this. And sometimes you get some great suggestions from non obvious team players. And the other thing I do, I say this a lot. I come up with a lot of crazy ideas and throw them out to the team sometime and I tell them, I want you to tell me why I am wrong here.
And it's not because I'm arrogant about it at all.
It's more around. Sounds good to me. But please, yeah, let's tighten up the thinking. Please tell me if I missed something here and if I didn't, let's think about this a little bit more. I would like to think in doing so that I create an environment where all of our team members at whatever level feel like they can just be open with their thought process.
[00:36:35] Speaker A: That's not a bad recipe for job satisfaction either.
[00:36:38] Speaker B: That's right.
[00:36:39] Speaker A: All right, Woody, I think let's finish there. Woody Bryant, it is, it is a pleasure to have you on few and far between. Congratulations on the recent announcement and exciting days ahead.
[00:36:48] Speaker B: Thanks, Chris. I really enjoyed being here.
[00:36:50] Speaker A: That's great.
[00:36:50] Speaker B: Thank you so much.
[00:36:55] Speaker A: Welcome, producer Adam.
[00:36:56] Speaker C: Hey, Chris. So just a great episode with Woody. Lots of information here to unpack.
[00:37:01] Speaker A: Oh, fascinating.
[00:37:02] Speaker C: Let's start off with maybe more of a biotech aspect of the upstream and downstream levers in fighting infection. I mean, it seems like a logical approach, but when Woody was discussing it, it really sounded like, you know, a very innovative idea to, you know, make use of all of the pieces when fighting these diseases.
[00:37:22] Speaker A: Yeah, I completely agree. I mean, I think a lot of times powerful ideas are obvious in hindsight if they are different from the way in which we've done stuff. Typically, it's really hard to change your thinking and break out a little bit. And it felt to me like that's what these guys are trying to do.
[00:37:36] Speaker C: Yeah. I also wanted to talk about his statement about not having to have a huge percent of the market to be successful. I mean, are novel approaches to niche markets still a viable strategy now?
[00:37:48] Speaker A: Yeah, I think so. I mean, I think niche markets is exactly right. I think you have to look carefully. It's a theme we've heard from a bunch of successful CEOs like Woody. You've got to have an economic thesis for the company. Right. So that works if the thing you're solving or addressing is important enough that people are willing to pay a fair amount of money for it. So you can still build a company that can cover its costs and return value to its investors, which is the name of the game. Right. You have to both help people, but you also have to do that in a way that's profitable so that you can afford to motivate investors to do it and, you know, deliver them a result at the end that makes them happy, too.
[00:38:23] Speaker C: That completely makes sense. It kind of brings me to my next point. You had mentioned during the podcast about. About thoughtful risk, and I think that that state really kind of defines our role as a company, you know, making sure that whatever, you know, opportunities you're going to take, that you have someone behind you to actually support you and make sure that whatever risk you're taking is managed.
[00:38:44] Speaker A: Well, yeah, that's 100% right. Maybe we should use that as a tagline. Adam, you can't eliminate risk from a venture as complex as developing a drug and bringing it to market. You can't even eliminate risk entirely from a clinical trial. There are things that that can go wrong, surprises can happen, et cetera. But you want to be thoughtful about it. You want to understand those risks. You want to do everything you can to de risk the things that can be de risked. That's a really interesting part of Woody's story. Right. Earlier in his career, looking for ways to start partway down the path to an approved drug with some questions already answered. That obviously changes the odds of success pretty significantly. So, yeah, a thoughtful approach towards risk I think is critical.
[00:39:25] Speaker C: So I was very happy to hear Jonathan Rigby's name mentioned on the podcast.
[00:39:28] Speaker A: Was I friend of the pod? Yeah.
[00:39:30] Speaker C: I had no idea that everybody, you know, I guess everybody knows everybody. I mean, it would be Great to have them working on a project. Of course, you know, it's interesting when you're working in this industry and you have friends and colleagues and to maintain that friendship in situations where you might even be a competitor might be kind of tough, you know, despite everything thing. Your thoughts on that?
[00:39:51] Speaker A: Yeah. One of the things that I love about the industry that we work in, okay, there are jerks everywhere in every industry and walk of life. But please don't stop listening there, listener. I think there are proportionally far fewer jerks in biopharma than you find in some other industries. I think something about the mission that draws people to work in human biology and try to cure diseases and try to solve problems for patients and the collaborative nature of a of lot, lot of successful medicine means that while again, nothing is perfect, there are a lot of nice and collaborative folks. And a lot of the success that people have, and we've heard this a number of times from folks on the pod is from their mentors, their peers, folks that they were in grad school with, folks that they worked with in a previous venture, et cetera. And forming those and building, developing those relationships ends up creating something really powerful in the culture of the companies and even sometimes in seeing around corners and avoiding problems. So I'm not surprised that these guys know and like each other. Lots of other folks in this industry, I think, have their own Jonathan Rigby's, et cetera.
[00:40:51] Speaker C: I hope they do. I really hope they do.
[00:40:53] Speaker A: Yeah, it's probably worth mentioning, Adam, that like, it's actually not a bad goal. If you're listening to this and you're thinking, I don't have a group of mentors and advisors, I don't have a kitchen cabinet for my career or for my company, you should be working on getting one and no one's going to drop it in your lap. You get those by adding value for people, staying in touch with them, helping them, cheering them on and asking them to do the same for you. I think that's, that's probably a pretty important takeaway.
[00:41:19] Speaker C: I completely agree. And it really needs to go beyond networking and into, into a friendship to really turn that relationship into something solid. So good point. So finally and slightly off topic, I did some research about the pillars of society. And so when you're talking about the pillars of society, you have doers, you have thinkers, and now you have these builder creator things. Yeah, I think the one that's missing is, is decider. I think that's another one. Do you feel like when you have all of These defined moments within something that is applied to how different roles are in your business. How do you move beyond something like that? How do you stake your claim into a specific role? I think it's a, it's a great opportunity for advice in those situations.
[00:42:05] Speaker A: Yeah, it's a really good question. So first of all, I think that the builder creator role contains the decider role in it because, you know, successful builders have to decide what not to do. That's as important as what to do. Whether they're starting a business or creating content or growing a business or whatever, turning it around, whatever it might be. Leaders should be spending a lot of time thinking about what do we not want to do and how do we make efficient and effective decisions so that the company can move quickly to achieve its objectives. So I think that's where it lives, is inside of that place. And then I think very few of us are 100% one of these things. And I'm not sure there are, I suppose there are some people who are 100% creators.
[00:42:44] Speaker C: Right? Right.
[00:42:44] Speaker A: You're a writer or painter or something like that. Maybe you're pretty close to 100% a creator. But even a lot of people who are in fields like that also spend time doing, you know, having to do stuff, get stuff done, managing things, making decisions, etc. So we probably all spend some time in all of those different quadrants. I think it's not a bad bit of advice to say think about your own career and think about which of those quadrants you spend time in and which ones you'd like to spend time in. So, you know, the doer one can be really important. If you don't have people who are actors in the world who get stuff done, nothing happens. So being able to execute efficiently and effectively is a really valuable, can be a really valuable set of skills. On the other hand, if you do the wrong thing really efficiently, that doesn't necessarily get. Get you to a great place. So being able to think about what the right solutions are and being able to make good decisions, all that stuff is important also. So thinking a little bit about what's my mix, do I want to shift that mix over time? Who are the people in my life who are good at the things that I want to get better at, how do I spend more time around them, stuff like that. And then I think inside of an organization, you have to have a mix of all these different characteristics and a category of CEO that I have seen who fails is somebody who says everyone should be like me, a really clever creative thinker, let's say those tend to be organizations where not much gets done. And similarly, if somebody does not see themselves as a creative thinker and idea person and they only want people who are pragmatic and operationally oriented, they oftentimes don't see the next problem coming. The guy that's gonna come and eat your lunch. So, you know, we probably all should spend some time thinking about the balance.
[00:44:15] Speaker C: Awesome. Again, a really interesting episode with Woody. And we'll be back with more episodes later this week.
[00:44:21] Speaker A: Month. Yeah, lots of wisdom from Woody. That's, I think, the bottom line. All right, Adam, thanks very much.
[00:44:25] Speaker C: Thanks, Chris.
[00:44:31] Speaker A: Thank you for listening to the latest episode of Few and Far Between Conversations from the Front Lines of Drug development. Our podcast is now available on Apple Podcasts and other streaming services. Please take a moment and leave us a user review and rating today. It really helps people discover the podcast and we read all the comments. Those comments help us make Few and Far between better and better. Also, be sure to subscribe to Few and Far between so you don't miss a single episode. Got an idea for a future episode? Email us at fewandfarbetweeniorossi.com or contact us on our
[email protected] I'm your host, Chris O'. Brien. See you next time.
