Talking Biotech Podcast 366 - New Therapeutics for Novel Problems through Collaboration. Dr. Betsy Oneill, Hortzon Therapeutics
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Kevin Folta: [00:00:00] Hi everybody, and welcome to this week's Talking Biotech podcast by Collabora. Now, one of the joys of hosting a podcast on biotechnology is that every week I get to geek out on an amazing new approach to solve an important problem. The new tools are super innovative, and each breakthrough has the potential to spur thousands of new approaches to a wide variety of important problems.

And this is why biotech startups are. And while yesterday's new technology is rapidly morphing into tomorrow's or later today's, uh, solutions, the tools and innovation are there, but moving them to application takes a certain flavor of expertise, whether it's raising capital, managing teams, or uh, the business end, or dealing with regulatory issues.

It's something not every startup is good at or even excited about. Science is the fun part, right? At least for me. [00:01:00] But some companies have navigated these waters and can serve as excellent partners for those that have a product and wanna move it quickly towards the market need. Today's guest describes how her company is benefited from these kinds of collaborations where a new technology gets winded at sales from proven partnership.

Today's guest is Dr. Betsy O'Neil. She's the VP of External in. At Horizon Therapeutics, welcome to the podcast, Dr. O'Neill. 

Betsy O'neill: Thanks for having me. 

Kevin Folta: Yeah. Well, this is a interesting set of topics because when we, we've been covering a lot of ground in the pharmaceutical area and in drug discovery, and there's still a lot of openings for.

New treatments and new therapies for different diseases. And a lot of these fall into the, the bucket of rare autoimmune inflammatory diseases. So why are these areas, in particular, areas for drug discovery and what are some of the key issues that Horizon is hoping to focus 

Betsy O'neill: on? [00:02:00] Well, you know, it's an area we really like because as science has progressed over the last 20 years, we've learned a lot more about the immune system.

I like to. With my colleagues that when I was in grad school, there was like T cells and V cells and not very much else. But these days, all of the work that's been done, there's so many different cell types and so many different molecules that we can target with drugs. That the, just the learning in the field has been explosive and that's really allowed us to go, you know, 20 years ago there was a lot of focus.

You know the big autoimmune conditions like rheumatoid arthritis, psoriasis, et cetera. And as we've learned more and more about how the immune system works and what drugs can target, which cell types, we've really been able to narrow down into some of the smaller diseases, which are actually can be very, very severe.

Lupus, Lupus nephritis, derma myositis. There's a bunch of different diseases that have very severe [00:03:00] consequences for the patients who have them. Previously there was very little work being done cuz of small populations, but now we really understand things so much better that there's a lot more activity in clinical development.

A lot of people are looking at molecules for these diseases. 

Kevin Folta: Are there other, like of the main. Diseases or disorders that we don't consider to be autoimmune, that have autoimmune edges to them so that you have some sort of a, a dysfunction that leads to other problems that are related to the immune system.

Betsy O'neill: I mean, we tend to focus on ones that have more of a direct autoimmune component. There are some, there's a, there's an interesting kind of intertwinement I would call it, between autoimmune diseases and fibrotic disease. So there are some, uh, diseases that have maybe an autoimmune. Component or a immune response that triggers a, a fibrotic response and then a tissue becomes fibrotic and that causes a specific type of pathology.

And that's a [00:04:00] newer area where people have been thinking about it for a while and done some work, but it's a tougher area to really get traction on the drug side. So our early stage group is looking closely at fibrosis as well as newer autoimmune 

Kevin Folta: mechanisms. And when you talk about these rare diseases or these, you know, small, I hate to say it, you know, from a business standpoint, but that's where we are, a small market diseases where you have a very limited number of, of potential people affected.

How much of a problem are these? In terms of, so I know it sounds callous, you know, there's just a couple people, or you know, smaller populations that have it. So big companies are not willing to get excited about the expense of r and d process to solve a problem that not that many people have. They focus on big ones.

How many, uh, how much of this is a problem in what you are looking at for drug develop? 

Betsy O'neill: Well under the FDA rule, a kind of an [00:05:00] orphan to get orphan drug designation, which is a special designation granted by FDA for drugs to treat rare diseases. Uh, it's patients fewer than, fewer than 200,000 patients in the us so it's still fairly big.

You get down to, we would consider maybe ultra rare. Type of diseases that get more into the like hundreds or like single digit thousands of patients, you know? And. There's different ways to address, that's, that's kind of a big range of patient numbers. On the larger side, you can still make some decent revenue with an acceptable price point.

When you get down to the very ultra rare ones, you wind up getting a, a higher price point. But some of these diseases are very, very severe and the, you know, there's a science called pharmacoeconomics where. You kind of balance, uh, what's the benefit of the drug and, and what's the suffering of the patient without the drug.

So some patients with very, these very ultra rare, very serious diseases actually can be a [00:06:00] very expensive burden anyway. So you can justify economically, you know, a price point that works both for payers and for patients and these very, very small diseases. Horizon in particular, do we, We don't do ultra rare.

Per se. Uh, some of our drugs may wind up working in an ultra rare type of setting for immune diseases, but a lot of the ultra rare ones tend to be more like genetic diseases, which is not a focus for our particular research team. 

Kevin Folta: Well, right in your title, you are the Vice President of External Innovation, and what exactly does that mean and what kind of products do you focus?

Betsy O'neill: Well, you know, we decided to actually create a department and name it external innovation. The reason for that is because, you know, we have a very strong, capable group of research scientists, clinical development experts in our r and d team. We have very. Great, talented folks, but it, there's always, however good your internal group is, there's always [00:07:00] gonna be more people outside that are also smart and capable and talented.

And the only way to sort of keep track of all the exciting developments and be able to participate and you know, when new science comes out. Is to have a group that's dedicated to looking externally. So we look externally and we bring in opportunities for our internal team to evaluate. And so we're always kind of on the hunt for new drugs and we work very closely with our business development team and licensing group, um, to bring in, It could be.

A very early stage research project. It could be a drug that's undergoing clinical development, or it could be even an approved drug. So we look across the gamut, but our remit is to focus what's new, what's exciting, what fits our strategy externally, and how can we work on bringing it in house. And taking advantage of, uh, the capabilities and skillset that we have at Horizon to make the drug more successful.

So a lot of smaller companies [00:08:00] may have really great science, really great ideas, made a really exciting potential drug, but they may not have the finances or the operational ex ability to execute the these big. Global clinical studies, you need to get global approvals and we really have that. So it can be a really nice partnership where each party kind of does what they're good at is how I always like to frame it.

Like if we find interesting science, we say to them like, How can we make this better? What can we do to make this drug be better? I 

Kevin Folta: see. So do you have some example of different companies you might be collaborating with and what kind of projects you're currently working on? 

Betsy O'neill: Sure, sure. We've got a couple early stage ones that we're working.

Um, we have, uh, we on the, on the research side, pre-clinical for the really novel new cutting edge stuff. We actually, um, have a couple different target discovery collaborations. We would frame it as where we're trying to find like, What protein in the body could we target with a [00:09:00] drug that would help treat a disease?

So for example, we have a one on gout targets with a company called Hemo. She, um, and then we also have a collaboration with a company called Alpine Immune Sciences. And that one's actually a drug discovery. So there we have ideas for targets that we wanna go after, and they have this really great, um, scientific approach for generating drugs.

They can be. Bi specific or multi specific. So it's kind of a multi two armed, uh, biologic drug that actually can touch two different targets and maybe bring cell two different cell types into close proximity. Or you could bring two different receptors on one cell. Next to each other to stimulate signaling through a pathway.

So it's a kind of a newer approach. We call it bifunctional that we're working with Alpine on. So those are two preclinical examples. 

Kevin Folta: That's a really good one. And what about with, uh, academic institutions? So, you know, as an academic scientist, I, I see so many interesting [00:10:00] opportunities to integrate with companies that have the firepower to elevate our.

You know, beyond what we can do from state, federal, or local funding. So what, what kind of, uh, partnerships are useful in an academic context? 

Betsy O'neill: Well, you know, there's a bunch of different types. Uh, it can be, uh, what I would make a bucket, I would say sort of tools. So academics are great at building out like mouse models and really getting under the hood and looking closely at a lot of biology.

So we can really collaborate, like if someone may have developed a mouse model for a particular disease, but they don't have the capability to make a drug, so we may have drugs. So that's again, like a great collaboration. They have this really interesting mouse model with which reflects disease pathology, and we have like four or five different molecules.

We're not really sure which one's gonna be the best drug, but we, if we test them in the animal model, Then we can find out like what's the best idea? And that can extend to other types of things [00:11:00] beyond animal models as well. It could be a really cool cellular based assay, or it could be some really cool imaging or, you know, the latest PET or mri or MRI type of technology for scanning patients or, you know, diagnosing and, and, and profiling disease states.

So there's a lot of different. You know, really cool cutting edge technologies that happen at universities, but it really helps to bring in somebody who has like the, the, the molecules and the clinical development expertise to be able to take that forward and be able to spread it around to other centers.

Um, and, and other, and more patients. Access to more patients too. 

Kevin Folta: Yeah. This, you know, podcast is talking biotech. So we talk about biotechnology. What role does biotechnology play in the development of your, uh, pipeline or maybe just in the collaborations? 

Betsy O'neill: Uh, I mean, biotechnology is a very broad term. I mean, as an industry, you know, we're [00:12:00] Horizon Therapeutics.

I sort of consider us as a big biotech company. There's, and historically biotechnology referred to, um, biologic drug. So, you know, Genentech making the original kind of antibody drugs that was kind of differentiat. Small molecule pharmaceutical companies who maybe take a small molecule and make it into a pill with oral administration versus biotech, which was kind of, uh, meant protein drugs that are maybe IV infusions type of a thing.

So, I mean, both approaches can be very, very powerful. You know, you get a, a benefit of less frequent dosing with an infusion, but you have to go to the infusion center and get the infusion. They have different safety profiles. So there's a lot of differences. And you know, my viewpoint is like, we got a lot of diseases, we have a lot of people suffering.

Let's just hit it at all. The different, all the different, we call it modalities, whether it's a small molecule for a pill [00:13:00] biologic, for an IV infusion. We've got, we don't work on gene therapy, but I'm follow it very closely cuz I'm passionate about it. You know, gene therapies, there's all these different kind of.

Uh, modality and approaches to, to attack these diseases to help the 

Kevin Folta: patients. Yeah. So we're speaking with Betsy O'Neil. Dr. O'Neil is the VP of External Innovation at Horizon Therapeutics, and we're talking about, uh, what her company does in the area of new drug design for autoimmune and rare diseases, uh, about the specific roles of different kinds of partnerships.

And on the backside of the break, we'll talk. The new innovations that are actually hitting the ground and the pipeline of things to expect. This is Collabs talking Biotech podcast, and we'll be back in just a moment.

And now we're back on Collaborate Talking Biotech podcast. And before we return to our regular guest, we're going to [00:14:00] talk to Dr. Vega Shaw and she is planning a Twitter thread that will introduce you to exciting areas of biotechnology. So welcome to the podcast, Vega. Thank you. Yeah, could you tell me a little bit about your 

Vega Shah: plan?

Plan is to put out a thread featuring a startup every Saturday. So it's called Startup Saturdays. Um, with, with two goals. The first goal is to just highlight the amazing technology that's coming out of startups right now in biotech. Um, I live in the Bay Area and they're. 3000 biotech companies here.

Quite a few of those are startups. They're just doing amazing work. There's this rich ecosystem of startups. The other goal is to help folks in academia that are either working on their PhD or postdoc, uh, to introduce them to these new companies. So that they can imagine themselves in, you know, alternative [00:15:00] roles outside of academia.

Uh, I know that startups are often recruiting talent that are coming out of academia, so it's a very mutually beneficial relationship. Having a, a startup job right after you finish your PhD or you've done a postdoc is really great. You wear a lot of hats and you learn a lot of different skills in the private sector.

Um, so those are two goals. Um, we'll be doing this every week, a, a thread featuring a single startup. Um, I'll talk about, you know, what stage are they at, what's the technology they're working on, whether or not they're hiring, and what types of roles they're hiring for. 

Kevin Folta: That's really cool. So you're going to do this on a Twitter thread every Saturday about, uh, 10.

Pacific Time, which is what, 1:00 PM Eastern Time. And what kind of content will be in that thread 

Vega Shah: goal is to, uh, provide content, uh, that. Useful for folks that are, um, either looking for services [00:16:00] or technology to use in their research. So that helps the startups. Uh, but then also to provide information about what types of roles they're hiring for.

Um, that helps folks that are, you know, in academia and they can kind of. Get, get exposed to that information, um, and maybe even apply to jobs at startups. 

Kevin Folta: And if I'm a hot startup that wants to get on your thread, do I send you an edible arrangement or what do I do to have you represent me? , uh, 

Vega Shah: not edible arrangement, not necessary.

Um, just. Send me a message on Twitter and, uh, maybe a short blurb about your startup, You know, what's your technology and, um, you know, what, what you'd like to feature. I've been very open to most startups. Uh, I do want to kind of focus on certain types of startups, so, um, software sequencing technologies, uh, drug discovery.

But really those are just sort. [00:17:00] Um, broad, you know, broad goals. It, it, it's not as restrictive as that. So yeah, just send me a message. Happy to put folks on in the queue to 

Kevin Folta: be feature. , and I think you'll find a lot of audience for this. I get so many solicitations at talking biotech, there's no way I could possibly have 'em all on.

So definitely, uh, if you're a startup that's out there looking for more of exposure to, for your business, or if you're a student or postdoc or a scientist looking for maybe a different hat to wear inside the biotech area, uh, Vega's Twitter feed is an excellent one to check out. So where can they find.

My, 

Vega Shah: my Twitter handle, which is Doctor underscore Alpha Lira, d r underscore a l p h a l y r a e. 

Kevin Folta: I really love the idea. Twitter's a great place to be able to expose lots of professionals to your work and, uh, then maybe spread that on LinkedIn [00:18:00] and some of the other places where eggheads hang out and look for this kind of content.

So thank you very much for joining me. 

Vega Shah: Yeah, of course. Thanks for having me. 

Kevin Folta: And now we're back on Collaborates Talking Biotech podcast. We're speaking with Dr. Betsy O'Neil. She's the VP of External Innovation at Horizon and external innovation, as we talked about previously, is this idea of. Partnering with smaller companies and academics that maybe don't have the resources to be able to take their product to the next level.

And we are talking about potential pipeline and that kind of thing. Uh, what are some of your favorite notions that are working through the pipeline, which have come from those early stage collaborations? 

Betsy O'neill: Yeah. You know, here's another really interesting example that I like, we're we have a collaboration with a company called Arrowhead.

And their technology, uh, is called S I R A technology. And what they do is they actually take, uh, make a little target. It's a nucleic acid, and it [00:19:00] targets the mRNA within the cell. So if you have a. Uh, you know, a gene that you know is being expressed and it's causing a problem and you wanna knock it down to, to give therapeutic benefit to the patient.

You can take advantage of this kind of preexisting machinery in the cell that originally is used to kind of detect, you know, uh, new. Inappropriate nucleic acid in the body. So it'll knock down mRNA, like say from a virus or something like that. But we kind of can coattail onto it. And arrowhead's one of the companies who's developed this interesting S I RNA approach where, um, we, we design a little guide strand of rna, which goes into the cell and then attacks the mRNA for a gene of interest, thereby knocking down expression of that gene.

So, you know, in. Small molecule biologics world that we were talking about before. There's only certain targets that are amenable to having a small molecule interfere with their activity or a [00:20:00] biologic interfere. But with S I rna, you can kind of target anything you want cuz all of the proteins expressed in your body go through an an RNA stage at some point in time.

So, The trick for that one is getting good delivery of this S I R N A drug. And so Arrowhead, along with several others, have attached a, a galack, it's a carbohydrate moeity to the end of the, of the target drug that causes very good delivery to the liver. So if you have a liver disease, it's just like super quick and easy to knock down right now using this GAL Act targeted s I R A approach.

And a bunch of other companies, including Arrow Hat, are now looking into trying to target to other tissues cuz we know this S I R A approach is so efficient. And knocking down mRNA levels and knocking down protein levels of, you know, kind of any gene you want. So it's kind of turning from a what target should I go after game into a, how can I deliver my s i A to the right [00:21:00] tissue within the body game?

Kevin Folta: It's pretty exciting because we've spoken on this podcast with a number of companies which are using. Targeted nanoparticles. So lipid nanoparticles and this kind of thing, like the covid vaccine. Uh, essentially being able to target specific RNAs into specific tissues like cardiac tissue is one good example.

It seems like this whole I, this whole idea is really evolving very quickly if we can get RNA in the right place. Are there other examples other than the liver? 

Betsy O'neill: Yeah, there's plenty of other examples. People are going after a number of different muscular diseases. So muscular is a new area. There are some genetic diseases, uh, typically, uh, gain of function, sort of genetically dominant diseases where, uh, inappropriate gene expression is occurring, or too much of a particular gene as being expressed where you can go in and knock it down with s i r.

It's interesting that you bring up the Covid vaccines [00:22:00] because those are actually delivering mRNA, so it's kind of like the opposite, like the technology's kind of similar in a lot of ways, but on the one hand, you're delivering mRNA to get expression of a gene of interest. In the case of a covid vaccine, that would be like the antigen you want the body to make, you know, antibodies against to protect you against covid.

And in in these cases with the SI rna, you're actually knocking down a gene that's causing pathology in a patient. So it's kind of like two sides of the same coin, but they both have in common, You know, this kind of delivery challenge is a big piece of it on both. 

Kevin Folta: Yeah, actually we've been doing it in plants for a long time.

We've been taking, uh, well, some groups have taken, uh, s I RNAs and introduced them just with clay, nano particles, found them, the little pieces of clay and shot them. Uh, Mrs. Uh, Dr. Uh, Nina Metter in, uh, in Australia, and has it been able to suppress specific susceptibility genes, which lead to plant disease.

Interesting. Yeah, [00:23:00] so, so really interesting stuff because you know how to ignite those aspects of the plant immune system by, uh, removing or by at least these things become systemic, uh, after you introduce them. So, pretty cool stuff. Yeah, really cool. Wow, I didn't know about that. Yeah. Pretty neat. So what are some other good examples of collaborative partnerships which have given rise to new opportunities based on that collaboration?

Betsy O'neill: Well, maybe I'll talk about another one that we have. We, we recently announced a collaboration, uh, with a company called Q 32 Bio. There are private company out of the Boston area, and they have an antibody drug that they're, um, they're initiating testing in humans. So it's an early stage clinical.

Candidate and it's, it's against a target called I L seven R receptor alpha. Uh, so it's, so it blocks signaling through the i L seven receptor. And that's an interesting, um, it's an interesting case cuz it interferes [00:24:00] with the immune system in patients with autoimmune diseases in a way that we think is gonna.

Provide benefit. There's a lot of early animal data and whatnot, but look, makes this look pretty interesting. The thing that's a little bit unique about this relationship is that it's actually an option structure. So they're, they're, they're, we're funding the studies and they're performing the early work.

And if it, if those studies go well, then we, those small pilot studies, they're doing the early stage first in human. Testing in a small clinical study, we call it, we would call it proof of concept, to show that, you know, looks like the drug is working maybe through a biomarker versus ac, you know, dosing long enough to see clinical benefit.

And then we, if the data look good, then we have the option to step in and take it into a big, what we would call a pivotal study, which is the thing you need for the final approval through fda. So that one's interesting. Maybe a little bit more on the business aspect. Where, um, you know, again, but each [00:25:00] party's like, what are you good at?

Each party can do what they're good at. And that's, that's one thing we really like to take advantage in terms of our external innovation strategy is the do what you're good at. So they have this very interesting drug. They've initiated some early work and we wanna. Participate and see the data as it's coming out, and then step in to do the really big studies that require, you know, more operational scale and funding and all that, um, to be able to then bring it to patients.

Kevin Folta: Okay. Well, you know, so your model works and this is you as the. You know, vice president of external innovation and identifying these potential opportunities. But we have a pretty wide listenership of diverse, uh, diverse listeners. If somebody has a clever solution, are you actually solicited by others who come in and say, We have a new technology we think you would like to see?

Betsy O'neill: Oh, yeah, we do a lot of that. You know, part of my, the remit for my team is we will call sourcing of new ideas and we have actually a. Sort of [00:26:00] sourcing strategy that we undertake to try to go out there and. New ideas, whether it's from companies, whether it's from academics or from even like colleagues at the company.

Uh, we're really very proactive at trying to find good ideas, good new ideas. You know, there's a, um, I, I jokingly called speed dating. There are conferences in the business development, you know, area. Within biotechnology where you attend a conference and before you go to the conference, there's a, there's a computer interface.

You know, you can look through companies that may have some technology you're interested in, and then you can set up 30 minute meetings with them face to face. And so it's like speed dating. You get up in the morning and every 30 minutes you meet with another company for like two or three days. And then it's a really great way to get a really quick impression and figure out like which ones to prioritize for further evaluat.

Kevin Folta: And it is a really good approach because there's so many collaborations that can come from smart people getting together and Yep. I, I, I [00:27:00] totally believe in that. I think that it's a lot of fun to take people who, you know, have heads full of solutions and turn them loose on a common problem. And, uh, that kind of innovation maybe doesn't happen enough because companies are rather insular and protective of their IP and their strategies.

You know, how much of how much. Would we maybe benefit if we had more of this kind of open 

Betsy O'neill: collaboration? I mean, I think it's crucial actually. And it's one of the reasons why, you know, I mean there's many reasons why I'm glad Covid is over, but one of the reasons I'm glad Covid is over, cause we're back to the face to face forum where you can just sit in a room for 30 minutes and you know, each side has like sort of.

You know, prearranged ideas to talk about, but then you can have usually 15 minutes to just kinda brainstorm and throw, throw ideas around whether it's a new collaboration structure, it's a different application for the science. I mean, biology is complicated. Medicine is complicated. Like no one person is gonna have the solutions.

To, [00:28:00] you know, help patients with these very serious diseases. We see it takes a village from drug discovery to drug development, to manufacturing all of these pieces, and it's only by getting together and sharing information, sharing ideas. Is the best way to come up with solutions. I mean, I work at a company, I'm practical.

I actually have a bit of a patent background, so it's important to be able to get, you know, intellectual property and patents and all that. But you know, so that's a crucial piece of it. But I think being transparent and open to the extent you can really is the way to win. And it's only. Combining two and three and four smart heads together that you really get to the answers, um, that that sets to solve these complicated problems.

There's a lot of smart people out there, , but these things require more than one smart person to solve them, you know? 

Kevin Folta: No. Very true. You know? So can you tell me more about the immediate pipeline? So where are the, what are the current set of, uh, therapeutics and where are they in their different, uh, [00:29:00] stages of, of clinical 

Betsy O'neill: testing?

Sure. I'd love to tell you a little bit more about a couple of them. So, you know, and within our, um, we have a couple of different therapeutic areas, but one of the larger ones is under this kind of autoimmune umbrella. So it's kind. Some rheumatology, some dermatology, some nephrology. So targeting slightly different organs, but kind of underlying the molecular mechanisms are kind of in.

Immunology side of things. So I'll tell you about a couple drugs we have in our pipeline. Our clinical development, Clinical development pipeline right now. So one is called, you know, these generic names are are terrible to remember, but Daso dbe, it's called, we call it Daaz for short . And um, you know, it targets something called CD 40 L.

So any of your audience members, maybe if you took immunology at some point. I know I took it quite a while ago and. The CD 40, CD 40 L axis, it's referred to as the co stimulation pathway. And it's a place [00:30:00] within the immune system where B cells and T cells talk to each other. And if, uh, you know, your immune system, if you think about it, they're out kind of scavenging around trying to find infections, right?

I found a bacteria over here. I found a cell infected with virus over here, right? And once somebody finds something, they need to go tell all their friends to. Proliferate up and build up a big immune response, Make more antibodies, make more T cells to attack. Right. So this co stimulation pathway is like really at the core, really at the heart, um, of the immune system where the B cells and the T cells are together and they're like, Oh no, you won't believe what I saw.

We gotta take action guys, like marshaling the troops, if you will. So, um, that drug, we actually just recently announced some new data in Sjogren's syndrome, which is an autoimmune condition that affects more women than men, but it affects a lot of different secretary glands. So people tend to have very dry eyes, very, very dry [00:31:00] mouth, you know, they have to tape their eyelid shut at night and stuff.

It can be very serious. And it's a, it's a disease where nothing's really approved right now. So our initial proof of concept in that disease looks really interesting. So, um, we're gonna put that into big pivotal study and, um, try to get it approved and, and get that out to patients as soon as we can. And that one, you know, we're testing it out in some other settings as well.

We have a little bit of data in rheumatoid arthritis. We're looking at it in kidney transplant rejection. And this is one where, again, In these, we, we have this term we coin as pipeline and a product, if you will. So one drug where you can treat multiple diseases. It's, it's kind of a, a good like business synergy.

You know, where you got one molecule, you do all the manufacturing, the early stage testing, and then you can. Try it out in a couple diseases where you think that pathology is implicated. So we really like that pipeline and a product idea. And so those are a couple of the, [00:32:00] you know, CD 40 L diseases that we're going after.

And then maybe I'll tell you about a second drug we have, um, called again, which a funding name Dax Dab . These generic names we call this one, we just call this one Dax for short. So we call 'em das and. Um, and uh, this one actually binds to a type of cells called plasma cyto dendritic cells. It's a little bit of a mouthful.

We call 'em PDCs for short. And what those things do is they recruit these kind of affector cells, and they are, they produce tons of, um, interferons and other molecules that really help stimulate and amplify. The immune response. And so again, like this is a, you know, someone who took immunology quite a few years ago, , this is sort of a newer cell type.

You know, the b and t cells have been around forever and people have been working on 'em forever In this like core, you know, Co stimulation pathway with daaz is [00:33:00] super exciting. This one is like a little bit newer going after these cells that go out there and produce tons of interferon, which is helpful if you're having a viral infection, but it's not so helpful if it's the re result of an autoimmune reaction right where your body's inappropriately recogniz.

Uh, you know, a native protein and thinking that it's a component of an infection and worrying up a whole immune defense against it inappropriately. That's the kind of underlying basis for autoimmune conditions. So this one we think is really exciting cause it actually goes out there. It's an antibody based drug and it actually kills these PDCs.

So it just depletes them and then they can't be. You know, doing this inappropriate job they're doing of secreting all these molecules that are continuing to stimulate and amplify this inappropriate immune response. So, . We think that one's gonna be very exciting too. So let me give you some diseases for that one.

So, I don't know if you've heard of this one called Alopecia ata. [00:34:00] It's a, it's a disease where people have patchy hair loss on their, on their, on their scalp. It's an autoimmune condition. People don't realize that, but it's, you get multiple big, large bald spots potentially all the way up to, you know, all or most of the hair on your head can fall off.

And that one. You know, it can be pretty upsetting to have, have that experience, um, and then. We have a couple that are more kind of, uh, uh, affect the skin a little bit more domato. There's one called DMA Myositis, which has both a skin component and a muscle component. Again, autoimmune mechanism. Lot of evidence for these PDC cells in that one.

And then we kind of have three different clinical studies that are theme and variation on an autoimmune condition called lupus that you may have heard of. Um, and they. That's a, it's a tough to treat disease cuz patients with lupus can have different organs affected. So, um, some patients have this, uh, thing [00:35:00] called OID lupus, which is actually a skin manifestation of lupus.

Some people have something called lupus nephritis, which is a kidney manifestation that can be very serious and hurt your, you know, your kidney function. And then there's actually systemic lu lupus as well where you know you have multi-organ involvement. So we're looking actually at all three of those, each and a different clinical study.

And again, we're very excited about those. We don't have the data back from all of those yet, but we think there's a really. Really high potential, um, you know, for these things to work out. We'll see, you know, you, the data, the, the, the data is what'll tell us in the end, but we, the science is so interesting on this and we can't wait to see the data coming.

Well, 

Kevin Folta: it seems like this really x at this razor's edge of the immune system, that when you're talking about t and b cell communication through the, uh, CD 40 L uh receptor and all this stuff, if you start to, uh, inhibit [00:36:00] that communication, how much do you affect immune response that is appropriate? So something like covid, you know, uh, sars.

CO two comes along. And can you still mount an effective immune response, or at least let's say a long term, uh, uh, immune memory because of the BCE involvement? Mm-hmm. when you, when you have, uh, a standard infection that shows up. No, 

Betsy O'neill: that's a really great question. It's a really important question as well.

And one of the challenges with going after any of these kind of immune mediated, um, diseases, autoimmune conditions, is it's always a balance between. How much am I helping the disease pathology against? How much am I putting a patient at risk for a more severe infection? You know, you watch all these TV commercials and they have all these like risks at the end, but the risks are real.

And you know, we only treat, we, we treat almost exclusively patients with very, very serious diseases. And you know, they have to talk with [00:37:00] their doctor about like, what's the trade off here? Between, you know, what symptoms am I having and. Pathology is being caused by my disease and what's the risk of an infection?

Secondarily, it's also if I get an infection, what happens? So for example, you know, like with Covid it's was very, very, very scary early on and it's still scary. But now we can have, you know, kind of these antibody drugs or the small molecule. You know that, that, that your doctor can give you a therapy to treat the infection, right?

So if you gotta, if you're at higher risk for a bacterial infection, as long as those infections are responsive to antibiotics, you know, your Dr. May decide that that's an acceptable trade off. You know, so it's only if you were to get infections that are hard to treat is more concerning. So that's, it's always a balance.

You know, I wish, you know, as someone who works in the pharmaceutical biotechnology industry, [00:38:00] I wish I could provide people with a silver bullet, a drug that doesn't have any side effects. But these are, you know, these are biologically active agents and they're very powerful drugs and you know, you always are gonna have some kind of balance between safety and efficacy.

We work really hard in the background in the lab to try to tweak it so we get the efficacy as much as we can get and minimize safety risk. But it's hard. It's kind of, it's kind of impossible to get a perfect drug in that. 

Kevin Folta: No, I totally understand that. And I, I know of people who've had lupus. I knew someone who had ms mm-hmm.

uh, years ago where they had a very nice drug that came out that was an excellent therapeutic for MS. Antibody based, but, uh, but could cause in a rare number of cases, An extreme type of brain cancer. This PML stuff would show up and it took the drug off the market for a while and uh, he was devastated by this because he had finally had a therapy that [00:39:00] worked.

Eventually he came back with one of these black. Box registrations where they would allow the drug. But it was, uh, here you had something that worked. And his opinion was, I'll take my chances with the drug because, uh, because because it's giving me the relief I need from the problem I have. I'll risk the problem.

I don't have, 

Betsy O'neill: You know, it's, it's so interesting that you raised that example. I remember that case when that happened. You know, there was actually an advisory committee at the FDA where, you know, uh, they pulled it from voluntarily, pulled the drug for a year and looked into, you know, my point earlier, is there some way we can treat this disease?

They were doing like plasma exchange to try to pull the drug out of circulation and figure out ways to treat it. Right. But when they went back to fda, To talk about it. What happened were they had, there's a, a, any kind of advisory committee like that, there's a port FDA presents for a portion, the company seeking approval for drug presents for a portion, and then there's a portion that's [00:40:00] dedicated to patients, kind of members of the public.

It's typically patients or representative of patients groups. So many patients wanted to talk that they had to schedule a second day for patients to come back a second day and talk some more, and everyone was saying exactly what you're saying, which is. Uh, we realize this is a risk, but it's extremely rare and they're working on ways to treat it.

So don't take this drug away from us because I have multiple sclerosis. I'm gonna wind up in a wheelchair. I mean, we, there literally were patients in that clinical study who had been in wheelchairs who were up and walking again and had independent mobility after taking that drug. So it's a very, It's a funny that you mentioned that case, cuz that's actually kind of a, a very well known case in our industry.

You know this hard conversation between safety and efficacy. 

Kevin Folta: One of the other benefits of working as identifying small companies with kind of niche therapies for important diseases to small numbers of people is the ability to change the lives [00:41:00] of people who maybe suffer from a given ailment or given problem.

It isn't going to be looked at, uh, by most pharmaceutical companies. So could you gimme a couple more examples of where this, this model really works? 

Betsy O'neill: Yeah, Kevin, I mean, one thing that's a little different, you know, in terms of innovation, a lot of companies in our sector will start from some very interesting science in the lab, and then they'll move into clinical development and then they'll move through to commercialization.

I would con consider that as kind of the. You know, the typical model of how, uh, you know, a new biotech company is formed, generally speaking. Um, but Horizon Therapeutics is very interesting in that we actually were built in a reverse direction. So our company was founded. By a small group of folks with commercial expertise and they had an original drug that was a, you know, a smaller drug to, to treat um, uh, inflammatory [00:42:00] pain.

And they sold that drug and it was profitable cuz they had very small r and d, you know, group to support that cuz the drug was already approved and they reinvested that back into this rare disease model, you know, which is sort of 10 or 12 years ago. And they started licensing in drugs that were approved for very rare, very serious diseases, and took their commercialization expertise and used that to kind of make sure as many patients as possible, really getting access to the drug and then, From there, they started licensing in, uh, clinical stage drugs.

The first one being our dr. Our medicine we have for thyroid eye disease. You know, it's a, it's a disease that's treated by, um, oculoplastic surgeons who, you know, the traditional therapy was by via surgical procedure for that disease. Mm-hmm. and. [00:43:00] The, uh, a small company had been founded to look into it and they had some very interesting early data, but a lot of the other, you know, they sort of, you know, uh, looked around for someone who might be interested in partnering with them.

And a lot of the other companies passed on the opportunity cuz they. We're looking for, you know, something more traditional like, we want a drug for rheumatologists, we want a drug for dermatologists, et cetera. And this oculoplastic surgeon was a very small group of folks, but it's a very serious disease and there's a pretty good number of patients that have it.

And you know, I was not at the company at the time, but I remember watching the story in the news, and I thought it was so innovative of Horizon to be able to take a chance on this. Group of physicians who typically do surgery and don't even write prescriptions for complicated drugs and try to convert, you know, patients have to undergo this surgical procedure where, you know, the, the, the surgeon has to sort of take your eye out and [00:44:00] scrape away this fibrotic tissue that surrounds your I optic nerve and then kind of put your eye back into the socket.

And we, you know, these guys came up with this medicine. To do it instead. So I thought that was very innovative and I was really impressed that they kind of took a chance on this, um, disease that there were no, no one else was looking at drugs to treat and converting something from a kind of painful surgery.

into something that could be treated with a, with, you know, six, six month course of infusions instead. So I thought that was pretty innovative and they've just kind of built on the success from there. There's several other examples of, um, you know, drugs they brought in along the way. We have a, a drug for very, uh, a medicine for very severe gout, which was also in licensed, had just been approved and.

Our co, again, our commercial organization was actually really pivotal in helping doctors understand how to best use the drug. It's a little bit complicated drug to use, so really needed some support to [00:45:00] get it to be used right, to really benefit patients that have these. Scouts a, a disease caused by accumulation of too much, um, serum uric acid.

And it can get to the point where patients actually grow crystals of uric acid in their joints. So it's kind of considered as a form of arthritis cuz you get this severe joint pain and it's kind of like, A basic biochemical situation like forming crystals. It's like super saturation. If, and if you remember your chemistry class , you know, And um, this drug is able to really destroy a lot of that serum uric acid and bring patients back to having much better functioning joints.

But it's a little tricky to use in our commercial team really. Uh, Was, it was, um, crucial in, in, uh, getting it out there and getting so many more patients using it. 

Kevin Folta: Well, Dr. Betsy O'Neil, thank you very much for joining me. It's really impressive how this kind of collaboration can lead to new products for niche conditions and really form a, a nucleus around [00:46:00] conditions that need some attention.

So if people wanna learn more about Horizon Therapeutics, is there a website they can look for? And where are you in social 

Betsy O'neill: media? Sure, of course. Come. Just go to horizon therapeutics.com. You know our innovation section, there's a business development page there where you know new ideas can come in through that.

Uh, we're also present, of course, on LinkedIn for Horizon Therapeutics or on Twitter. You can look, you can find us under Horizon News. Is our handle for Twitter. 

Kevin Folta: Very good. Well, thank you very much for joining me today. I really appreciate your time and if you, uh, have big breakthroughs, I should say, when you have big breakthroughs mm-hmm.

uh, let me know and we'll be happy to talk about 'em here. All 

Betsy O'neill: right. Great talking to you today, Kevin. Thanks. And 

for 

Kevin Folta: everybody else, thank you again for listening to another week of Talking Biotech podcast. Remember that the diseases that don't make the front page are still affecting some folks and that it's important that small companies are carrying that mantle.

Or [00:47:00] maybe the payoffs aren't great and the road is just as rigorous to drug development. But companies like Horizon Therapeutics are lending their expertise. To help make that transition to the marketplace a little bit easier. This is a Talking Biotech podcast, and we'll talk to you again next week.