Hello, I'm James Stamos. I don't think the mic was working. Yeah, it's good.
Hello, everyone. I'm James Stamos, representing Moy Raycroft, one of the biotech analysts here at Jefferies. I'm happy to introduce and welcome Charlie Geyer, CEO of Biochrist. This is a fireside chat format. Thank you for joining us today.
Thanks for having us.
For those new to the story, can you please provide a one-minute introduction to Biochrist?
Yeah, Viacrist is a company that focuses on rare disease commercialization. We've got a product, Orlodeo, in the market for HAE, a prophylactic therapy, that did $602 million in revenue last year. And that's partly because of the product itself. It's a differentiated product. It's the only oral prophy drug in its space. But it's also just how we do the commercialization. We think we have a differentiated way of doing it, very patient-focused, and it shows up in the results in the market. We also have a late-stage asset also in HAE with Novenobart, which has the potential to be a best-in-class HAE prophetherapy itself. It has an every three- and six-month dosing profile that is in Phase III trials right now, getting ready for BLA filing at the end of 2027. And then we have an early-stage rare disease molecule in our pipeline for Netherton syndrome, BCX17725.
Great. Thanks for that. So let's just start off with Orlodeo. You maintain the full-year revenue guidance of $625 to $645 million for Orlodeo. One Q came in at the lower end of $148.3 million due to typical insurance dynamics. but what are you seeing in 2Q so far that gives you confidence in achieving the midpoint for the
full year? Yeah, actually, Q1 was right in line with our expectations. Orladeo is in the sixth year on the market right now, and we're at a stage where it's all about consistent new patient demand, and we saw that in the first part of this year. We're in year six, and we're seeing last year we actually had more new starts than we had in the first year of the launch. So that's going well. And then it's about helping patients get reimbursed. We are in the 80 percent. We finished last year at 82 percent of our patients are getting reimbursed. Every year we're making progress on that. And so that was a lot about a lot of what we were focused on in Q1. So basically everything's
going according to expectations. Any comments on likelihood of having to adjust guidance for 2Q
and what reasons for that could be? Now, like I said, we're right in line with where we expect to be. And, you know, we're on a longer term path of growth for Orlodeo and eventually have a whole portfolio here of HAE products that in the 2030s, you know, could be in the 1.5 to $2 billion range.
So we're on track. You've maintained the 1 billion peak sales guidance for Orlodeo, which includes pediatric sales and excuse EU sales. With the HAE landscape evolving, what are some of the key assumptions to support the 1 billion peak sales estimate? Yeah, for us to get there, we need to
average about 150 net new patients in the U.S. per year. Over the last several years, we've been above 200. And as you mentioned, we're adding the pediatric indication. Kids age 2 to under 12 have never had access to an oral prophotherapy before. So it's a market that we think can grow in terms of diagnosis, in terms of patients switching to oral prophy, and frankly using more prophylaxis in that population. So that's not the biggest driver of our growth, but it is an important driver in the next few years. What's your latest view on the total addressable market
for oral prophy, the oral prophy opportunity, and how much market expansion is driven by newly diagnosed patients or newly treated patients versus market shift from competitors driving growth?
What we see in the HAE market is for a rare disease, the patients are blessed with a lot of treatment options. There are 10 branded products in the market right now. And where things have moved is there's a segment of patients who really prefer oral prophylaxis, and then there are patients who have been on injectable prophylaxis for a long time, and that's the right thing for them. And so for Orlodeo, launched to date, a little less than half the patients have come from switches from injectable prophy. They would prefer to do it with oral. And the other, just over half, has come from new patient starts and patients stepping up to prophylaxis from treating their attacks on demand only.
Gross to net has historically tracked in the 15% to 20% range. do you see foresee any pressure on gross net as you negotiate broader formulary access to counter new injectable entrants? Have you seen any material changes in payer mix rebates or paid
paid rate? No, actually, our payer mix, just a level set on that is about 60% commercial 20% Medicare Part D. And the last 20% is mostly Medicaid, some other government, some truly uninsured patients. And that's been really consistent since launch. Gross to net 15 to 20 percent. Last year, we actually tightened it a little bit more. It was closer to 15 percent for the whole year as we're at the point in launch where we have the ability to really look at potential savings in all places. There's not contracting pressure on us so much, particularly now that Orlandeo has 1,600-plus patients on therapy. And so what payers recognize is this is the number two prophylaxis product, most prescribed product, in the marketplace. So we are in a much stronger position than when we were during launch.
For the pediatric launch, you had a delay due to batch-specific manufacturing issue. Is there a status update, and when do you expect to resolve the issue?
Yeah, we think we have identified the root cause, as we said a few weeks back. We thought that this was an isolated incident. It is, just with the quality of one batch, so it's not a safety issue. We've isolated the root cause, so we'll be manufacturing again soon. And we'll update our customers and the rest of the community when we have product in the pharmacy ready to ship. We think it will be in the relatively near future.
You noted you received prescriptions for all four strengths of the pediatric pellets shortly after launch. How much of a backlog is currently building and what's the expected contribution towards 2026 revenue?
So we've said before we were conservative in how we forecasted the pediatric portion for this year because we didn't know. We knew long term the demand is is really high for this group. We just didn't know how quickly it would come in. Early prescriptions have been ahead of our expectations, and so we've got a little bit of a warehousing of that, that when product is available, we actually think we'll be on or ahead of plan for our pediatric indication for the year because of that. And, yeah, the point about all four strengths, the Orlodeo pellets are weight-based dosing, so weight being obviously correlated with children's age. So the fact that we're actually getting prescriptions from the lowest as well as the highest just shows that this particular population is ripe for a treatment paradigm shift towards prophylaxis. And so we're enthusiastic about the opportunity over the next few years.
Key oral competitor Farvaris' extended release phase three prophy data is in 3Q. Can you walk us through scenarios for how the readout could ultimately impact early Dale's commercial opportunity? And what's your base case assumptions for what Farvaris will show?
Yeah, one thing we do, and we've done this since launch, is we do a lot of market research around the potential impact of current and future competitors. And in the case of future competitors, we like to take the conservative view for Biacrist and Orladeo. So we always assume that until we have a phase three profile or a final label profile, we will give competitors the best case. So we build in really good data for Decric demand from their phase two, and we assume that that's what they're going to get in phase three. And then even with that, we still expect to get to a billion dollars in peak sales because patients who do well on Orladeo tend to stay on Orladeo. The patients who don't get the efficacy that they're looking for, they move off to another product. And that may be one of the opportunities for Decryctiband. But we don't think that we're looking forward to seeing their data. We think it will be a very approvable product, and we're ready for that product in the marketplace.
Intelia recently reported phase three data for their gene editing program. Based on what they showed, how much traction or impact do you think this program could have?
We think that there will be interest from some patients. Our view, based on talking to the patient community, doctors, doing research on this, is it'll fill a niche for patients who have maybe tried other options, and those options just haven't worked for them. HAE, like a lot of rare diseases, can be tricky. Not every drug works for every patient, and so that may be a good opportunity for the Intelia product. But we don't see a kind of a groundswell of patients going toward that.
What has been the feedback from your field team on the broader adoption of oral on-demand ectorly impacting or potentially impacting Orlodeo?
What we've not seen is it affecting Orlodeo in any negative way. We do have patients on Orlodeo who, as we'd expected, are also taking ectorly to treat breakthrough attacks, but it hasn't changed the trajectory of Orlodeo. So we think it's a good option for a lot of patients. We've also not seen it necessarily improving the trajectory of Orlodeo,
just kind of no change at this point. Okay, let's move on to the Nevenobart strategy. Walk us through how you see the current injectable market dynamics, what share of prophylaxis patients prefer, subcutaneous options over oral, and why, and how do you see this evolving once Nevenobart enters
the market? So as I said up front, there's about 5,000 patients in the U.S. market who are already on injectable prophy. And so it's not a straight preference kind of thing. It's really more what are they used to. And just the way the market has evolved, Taxiro came into the market almost 10 years ago. It's a really good drug. And naturally, a lot of patients ended up going onto that and getting really good efficacy injecting every two weeks. Where Novenobart's going to fit in is it's a known mechanism of action as a caliprine inhibitor. It has the advantage of a formulation that doesn't have citric acid, so it's not painful. There's no injection site pain. And then it's got the three and six month dosing. And what we've seen in the phase two data is that that efficacy for both three and six months is very equal across the doses and very durable. So the patients are getting down to a mean attack rate of 0.16 per month in that open label phase two, which is less than two attacks a year. So when patients and doctors look at this profile, they say, oh, I get it. That's kind of a better version of what I'm already familiar with. And so the big segment will be these 5,000 patients, most of them who we expect to still be on tax iro, switching towards something that they feel is going to give them the equal, at least equal efficacy to what they expect, and a much more favorable
dosing profile. Are you still on track to complete enrollment of the alpha orbit phase three trial by the end of June 2026? And what more can you say about the types of patients you're enrolling? Are you observing trends in subjects transitioning from injectable therapies like Taxira or these largely treatment-naive patients?
Yeah, we are absolutely on track. The last, you can rarely say something like this, but I can guarantee that the last patient will enroll this month based on the screening period. The last patients are in screening. So we will be finished. It could be in the next few days. It could be, it will definitely be by the end of June. And what that means is the final patient will be through the 12-month blinded period by the end of June 2027. So what that means is we've agreed with the FDA that we're going to keep that blinded because of the six-month dosing profile. The six-month patients need to have that second dose. So we'll keep it blinded through then, and we'll have top-line data for both 6 and 12 months at some point in Q3 of next year. And that puts us on track to file the BLA by the end of 2027.
Nevenibart's key selling strategy is the every-three-months and every-six-months dosing frequency compared to TaxIra, which is biweekly, and then Dembri, that's as monthly. um how representative are the the venibart phase 1b slash 2 results with 84 at 92 percent mean attack rate reduction as it relates to what you expect in the pivotal and are there potential variables in the phase 3 that strengthen confidence or could add some risk on efficacy
slash safety yeah and just maybe to update on the data from phase 2 the the longer term phase 2 data that we presented at Quad AI back in February is the 92% reduction from baseline in a mean of 12 months for the three-month dosing, and a 90% reduction for the six-month dosing. And again, the six-month dosing is twice the three-month dose. So the commercial presentation will be a two-milliliter auto-injector, either one every three months or two every six months. So that's open label, but that gives us confidence in the durability of the product, and we would expect to see comparable efficacy in the pivotal study.
Does the BLA filing hinge on having the 12-month safety follow-up data?
Well, the good thing about the design is when that last patient finishes next June, as I described. This is actually the largest pivotal study ever done for HAE, and it enrolled really quickly, which I think is largely because of the profile of this product. And so at that point, we will have sufficient number of patients, not only through 12 months of efficacy, but 12
months of safety as well. Where does Nevenibart stand relative to the competition based on the data to date for other attributes like injection site reactions, immunogenicity, attack control,
safety? Yeah, so I did mention the injection site reactions, the fact that it doesn't have citric acid. We've seen this in the phase one and phase two studies that there's been essentially zero percent report of injection site pain, which is the real thing. Naturally, there will always be some minor injection site reactions reported as you'll have with any injection. But then to be able to launch with an auto injector it's a really you know simple and attractive profile from an immunogenicity standpoint you are always going to see these things in monoclonal antibodies the key is is your long-term data durable and that's where we're really pleased with this long-term phase two data it's showing patients are getting similar efficacy from both doses and it and it's it's been very durable all the other safety aspects that you look at have have looked very uh in line with what you would expect assuming approval in late 2027 or early
2028 how are you thinking about pricing and reimbursement for an event of art will you position it at parity with existing injectables like tax arrow or premium given the dosing
convenience uh just to correct so we don't get ahead of ourselves it would be great to launch that soon but it will file by the end of 2027 so most likely launch scenario is in the latter part of 2028. But, you know, this profile that I'm describing really has the potential to be best in class. Probably too early to talk about, you know, what we'll do from pricing, but at least I think parity will be very supported from a value proposition. And then back to something I said earlier about how we go about working with payers, how we generate evidence in the real world to support use of our products, we think we have the best model to get patients quickly to reimburse therapy, and that's going to be a key part of the launch. What market share do you expect to capture
in years one, three, and five post-launch? We haven't talked specifically about a forecast.
We've kind of echoed some of the analyst consensus for Nevenobart because we generally agree of their significant opportunity given our position in the market our experience it's all the same customers it's you know it's going to be our same team going to the same customers to launch an event of art and so that plus the profile of the product we think that this can have a faster ramp we will certainly be shooting for a faster ramp than orlodeo which has been more of a consistent growth story over the years as first the customers got familiar with Biocryst and increasingly familiar with Orlodeo. Great. So let's move on to Netherton syndrome.
For the upcoming phase one part four readout at your end, will you evaluate preliminary safety, systemic exposure, and early efficacy signals such as itch reduction and skin healing? What specific magnitude of improvement would you consider a home run situation?
Well, I think first of all, I mean, this is an incredibly high need disease. You know, These are patients who have no approved targeted therapies, and so they manage mostly with over-the-counter stuff. They, frankly, stop seeking care from physicians because the doctors have nothing to offer, and it's a horrible disease. You know, the skin barrier is affected. They have atopic conditions, asthma, food allergies, all sorts of things. So really, really high need. What we'd be looking for, a home run would be, we're going to have 12 patients of data by the end of the year, patients treated through three months. If we see very consistent effect across the patients, I think that would be the first part of the home run. The second part of the home run would be meaningful clinical improvement. And that doesn't need to be healing completely because, again, there's nothing out there. So, you know, for example, if there was sort of an average improvement of 40 percent or so in the global assessment of skin, and we saw consistent effect across the patients, and if we got some sense that we're narrowing on the right dose, that would be the home run. We don't have to have a home run, but this is the kind of product we will be looking for, something that clearly instructs us how to go to a pivotal study, that we clearly have a drug. If it's not clear, we'll move on and look for other opportunities.
And for the healthy volunteer data confirmed that the IV17725 successfully distributed to the epidermis, how tightly do you expect this target engagement to correlate with observable clinical healing once administered to patients with actively compromised skin barriers?
It was kind of a surprise and very interesting for us and certainly interesting for the investigators to see that the drug got to the epidermis in healthy volunteers. um we we didn't fully expect that and and so there's every reason to believe that the drug will get there at least as effectively in netherton patients um there's a possibility it could it could even be better in netherton patients but we have to we have to wait and see on that but it's certainly an encouraging uh signal for the for the drug and and importantly to the investigators They've seen some failed therapies in this area, but that one gave them a lot of encouragement.
Jumping ahead, what do you expect the pivotal trial design and regulatory timeline could look like for Neverton? Do you see potential paths to accelerated approval?
Yeah, it's probably too early to overly speculate. Lots of options. In rare derm conditions, we've seen drugs having pivotal designs that are open label and certainly more accelerated. It probably gets back to some of that, what uniformity of effect do we see? Our baseline assumption is we'd love to do a placebo-controlled just because it's gold standard that way. But we'll do that assessment when we kind of see the totality of our data at the end of the year.
What are your latest thoughts on the competitive landscape? Are there competitor updates you're tracking or expecting soon? And what have you learned from some of the other players out there?
Yeah, we're certainly, there's a company that folks may be familiar with called COIN, with a Q, that has a topical kind of pan-serine protease inhibitor applied twice a day. They've put a little bit of data out. I think they're gearing up to potentially file an NDA in the first part of next year. And so we're watching for that because, again, patients need options here, and we think that could be a meaningful option for patients. We also know from HAE and other rare conditions that patients don't just need one option. They need multiple options. And what we hear from patients and physicians is a systemic KLK5 inhibitor that we have. If it works, as I've described, that's what they would really consider best in class. But we're rooting for patients to get any kind of option as soon as possible.
What other indications or diseases could also be addressed by 17725?
Really early on that one, too. I think we're excited about Netherton's. We've done a lot of epi work. There's no ICD-10 code, so this is a bit of a challenge. But we've done some deeper claims and electronic medical records work. And it's given us a high level of confidence that there's 3,000-plus patients in the U.S. And like I said earlier, a lot of them just aren't seeking care. So once they have a therapy or two therapies out there, we think that this is a market that really has the potential to grow and is exciting in and of itself. If we have a drug, we'll look to see if there are any expansion possibilities. But this one would also be a very good standalone.
So let's now talk about BD and financials. You've been active on the BD front with the Astria acquisition, EU, Orlodeo, Divestager, and Nevenobart out-licensing deals. Are you open to further in-licensing assets? If so, what therapeutic areas or asset profiles, like small molecules, biologics, are you most interested in?
Yeah, we're absolutely active and open. um you know the way we with netherbart in the late stage uh development right now the next thing we do we'd like to bring in something that is later stage so not as much clinical regulatory risk we're pretty agnostic at this point from a from a therapeutic area standpoint we think we've got our hae portfolio so it's it's not that it also doesn't have to be the same customer base if we have success with nethertins, we might look at rare derm. We might look at something completely different. The key is it's got to be a disease like HAE where we can apply some of the same ways of commercializing, where we've been very successful and we think we can learn a new space and bring the same skills there. It's got to be a differentiated product, so oral or injectable, were agnostic to that, probably wouldn't do gene therapy, editing, cell therapy, those types of things. And then the other interesting thing for a company like us, we're profitable. We were profitable last year. We're going to be profitable this year. We're going to be more profitable next year. So our capacity is growing over time. And we don't need the next thing to be a blockbuster. It could be a $300 million peak sales opportunity that might be below the radar screen of others. but for us putting it through our commercial commercialization engine highly profitable and we'd like something else that would contribute to revenue growth ideally by the end of this
decade. With 2026 non-GAAP OPEX guidance of 450 to 470 million and revenue guidance of 635 to 660 million you're implying 165 to 210 million in operating profit. Is that the right math and And is that sustainable as you invested in the Nevena BART phase three and prepare for launch?
Yeah, that's absolutely the right math. And it's very sustainable because if you think about Nevena BART, we're in the later stages of the development there. So, you know, over the next couple of years, that's going to come down. Where we are right now as a company is we see that level of OPEX being kind of the baseline we want to stick with. You know, we don't need to grow GNA to do more commercialization. We don't need more sales and marketing to launch Novenobart. It's going to be the same team, kind of the same spend, and we just convert some of what we're doing on Orlodeo as it's reaching maturity over to Novenobart. And so the operating leverage there is growing significantly. And then that allows us to do BD or to gradually build a pipeline, maybe looking for earlier stages of assets. But again, we want to keep that profitability and keep the operating leverage growing.
So in the last few minutes, in closing, what is your cash position, your runway, and what are key catalysts over the next six months that investors should be focused on?
Our cash position pro forma at the end of Q1 after we licensed Nevenobart in early Q2, but pro forma back to the end of Q1 is $330 million. and like i was just alluding to we are we are getting increasingly profitable profitable so things things are actually growing uh so our runway is in our control um it's not it's not a cash runway thing it's it's about what do we do with with this cash as as it's growing over the next six months the the things to look for i've kind of let the cat out of the bag on the full enrollment of Novenobart, but that, you know, that'll be done in the next, in the next few weeks. Obviously, we have quarter, quarter over quarter growth in, in Orladeo. Getting the PEDS indication, PEDS product out there in the very near future is something to look for. And then at the end of the year, by the end of, of this calendar year, we'll have those 12 patients of data in Netherton's um to to see if we have a product there. Great thank you so much for joining us today Charlie. Thanks again for having us.