Rare Disease Drug Commercialization With Zevra Therapeutics' Neil McFarlane

On this week's episode of the Business of Biotech, Neil McFarlane, CEO at Zevra Therapeutics, talks about transitioning to a focused rare disease company through acquisitions, and building out a commercial organization. Neil explains the importance of working with rare disease patient advocacy groups, using AI to analyze electronic health records and claims data to identify and diagnose patients with Niemann-Pick disease type C, and adapting to regulatory inconsistencies around rare disease drug approval frameworks in the U.S. and Europe.     

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Transcript

Welcome And What’s Ahead

Ben Comer 0:03

Welcome back to the Business of Biotech. I'm your host, Ben Comer, Chief Editor at Life Science Leader, and today I'm speaking with Neil McFarlane, president, CEO, and board director at Zevra Therapeutics, a company developing and commercializing rare disease therapeutics for patients with unmet needs. We'll talk about the company's rebrand and transition from KemPharm's pro drug platform to Zevra's focus on rare diseases, and Neil's new strategy for the company upon joining as CEO in late 2023. We'll talk about key acquisitions and building a commercial team for rare disease therapies, working with patient advocacy groups, and the rare pediatric disease priority review voucher Zevra sold for $150 million in April 2025. And we'll get Neil's thoughts on the current FDA situation and the review process for drugs treating rare diseases, and what's next for Zevra. Neil, thank you so much for coming on the show.

Neil McFarlane 1:01

Yeah, Ben, great. Thanks for having me and uh looking forward to a special hour

Military Roots And Patient Mission

Neil McFarlane 1:05

here.

Ben Comer 1:05

Absolutely, me too. Uh, I wanted to start off uh with a little bit on your background. Neil, um, I saw in your uh in your on LinkedIn that you were an enlisted officer and soldier in the U.S. Army Reserves. Um, were you actually deployed?

Neil McFarlane 1:23

Uh not for any extensive period of time, but I was uh at both as an enlisted soldier as well as an officer on multiple missions uh outside of the United States.

Ben Comer 1:33

Well, thank you. Uh thank you for your service, Neil. I I bring that up because I was curious if there was anything that you learned from those experiences that uh that have come back to help you professionally in the life sciences industry.

Neil McFarlane 1:48

Yeah, you know, I I appreciate that question. I I get that one uh a lot. I also get the question that I'll hopefully try to weave in here uh because my background is uh is untraditional for certain in regards to the journey towards becoming a public uh CEO. And uh it did start uh in the military. I um as a uh teenager, I was able to join the Army Reserves as an enlisted soldier in the medical corps. Uh and throughout that process, I was actually also able to go to college and became a nurse and then a nurse practitioner, uh, and then on towards being on staff at the College of Medicine and the transplant program at the University of Florida.

Ben Comer 2:28

Okay, so the your healthcare experience goes back that that far.

Neil McFarlane 2:32

Yeah, well, that's what I was gonna get to, which is, you know, as we walk that journey of uh clinical practice, of uh the military experience, uh both as being an enlisted soldier and then obviously as an officer. Uh, and then you think about the biotech journey that I've been on that I'm happy to spend some time on. Uh, there have been a couple of key themes. Uh, one of them is impacting the lives of patients. Uh, and I did that in all of these journeys that I've been part of. And there's a triangulation between them all that I think is been resonating throughout my life and throughout my career and taking care of people, taking care of patients, but also being very mission-oriented uh in order to be able to accomplish, you know, the missions both in the critical care units or in the transplant settings uh that uh that I will talk about a little bit more later on, because the majority of transplants happen because of some type of end organ disease. And a lot of times that's from rare diseases. And uh and those rare diseases then uh you know uh people go on a journey and sometimes they're able to get new organs that help them get that gift of life to move forward. Uh uh, but that mission orientation, getting people around a table to to of all varying backgrounds, shapes, and sizes to be able to then execute on something uh with focus and and uh the ability to get the job done is kind of been the consistent theme. Large impact, patient impact, mission orientation.

Ben Comer 4:00

Yeah, you know, that that resonates with me what you're what you're saying about mission, and this is a completely different circumstance, but my wife told me recently, she's a uh a high school science teacher, and told me that the the smartest thing she ever learned from one of her teachers uh coming, you know, doing an education program, she's in a teaching fellows program, but was that to design the curriculum with an end goal in mind, to figure out what it is that you want to accomplish with these students at the end of a one-year period, and then build back from that, design the curriculum to reach that goal, which is a way that uh of teaching that I I hadn't that hadn't occurred to me, but seems really smart. And I I think what you're saying about mission in the healthcare space is is kind of similar. You're you're figuring out, you know, a strategic end goal, you know, for where you want to get, and then uh and then you're you know kind of walking through the steps uh to get there.

Neil McFarlane 4:56

Yeah, no, that's right. And and when you think about the mission, you've also got to find a way to get there, right? Uh and I think having the clinical uh experience and and having you know uh multidisciplinary uh working teams working together to be able to accomplish uh very complex treatment plans for patients with very critical diseases, uh, very similar to what we do today. Uh we're one part of that journey, but it's kind of what we do today. Similarly, in the military, you have operational orders, right? People from all walks of life. Uh, if you're trying to go and and become a um uh field hospital in the middle of the jungle, you need to understand where's your blood gonna come from. You need to understand uh, you know, how many operating theaters you might need. You need to understand uh the the amount of uh X-ray techs you need versus the amount of OR techs you need. And and all of that comes with the operational plan that then becomes an operational order to achieve that mission. What we do in biotech is not too dissimilar. Uh you have a strategic plan, and and it's very simple. Where do you put your resources and and uh and that's either people, time, dollars, uh, and and focus that effort into being able to accomplish what you what you set out to accomplish through the science, through the patients, through the clinical trials, through the financing, through the all of the the likes to being able to then deliver on on the uh strategy that you put out and achieve the mission.

Leading Through Teams And Operations

Ben Comer 6:22

Absolutely. Well, it sounds like you had a a strong uh training ground, uh part pardon the point, but a strong training ground for for this profession. I uh I wanted to ask you too. You've been um uh part of uh at least two MA, significant MA events during your career. Genzyme's acquisition of SangStat Medical, uh Supernus's acquisition of Adamas, where I believe you were CEO at Adamas at the time. Uh, what could you say about uh how those experiences shaped your approach to leadership and company operations? And I I asked because um, you know, acquisitions are are an important part of I think Zevra's company model.

Neil McFarlane 7:03

Well, I it's a really good point. And you you we're focusing on uh the ones where we we were acquired, and uh, I think throughout my journey I've been the acquirer and the acquiree. And uh and that comes with with teams, that comes with approach, approaches that uh are how does one and one equal three or four or five. And I think what I one of the one of the major learnings I took uh very early on in my career and remember, right? I um I have I was not a CEO throughout all of those journeys. I was a small part of of each of those journeys and and uh think about Gen zyme's acquisition of AnorMED. And uh I think you know I could go on and on and on of the both the acquiring and being acquired. And I think there have been a couple of really great lessons in this, which is it starts with people uh and making sure that you have the right people on both sides of the of the um ledger that allow for you to think about how to drive the science, drive the impact, drive the growth, maybe making sure it's at the right time in the growth of an organization, uh, that you have the right competencies. But most importantly to me is gets down to cultural impact or culture of organizations and how you then learn from each other to grow. You, you know, some of the best acquisitions that I've been a part of were small, but they allowed us to be able to learn from those organizations that we acquired. Some of the best, you know, I was part of the SangStat group that was acquired, and then I stayed with Gen zyme for many years. Uh, Genzyme was one of the the great uh training grounds. We'll keep using that dude here. The training, uh one of the one of the great training grounds for folks to be able to uh come into an organization that had a very clear mission on patient centricity and what you need to do in that community. But how can we grow from each of these uh acquisitions? How can we do better manufacturing? How can we learn new techniques for commercializing these ultra-rare products? And and for me, it was transplant-level products, uh, hematology, oncology products that we were bringing into the Genzyme system. How do you compete more effectively? How do you um uh uh uh learn on the geographic expansion uh that you were executing on a commercialization of products in Latin America differently than you were in Asia, than you were in Europe. So I think it really does come down to how much can you learn and the synergies you can get and having that open mind to being able to know that uh every one of these acquisitions you make has the ability uh to be able to be a force multiplier and the learnings in your organization to take it towards achieving your mission. We've learned that here, by the way, uh it at um Zevra in just a short period of time in a number of the acquisitions we've made.

Ben Comer 9:54

Yeah, and I I want to get on to uh to Zevra here in just a second, but I I like what you said about about culture and the importance of of that that aspect, whether you know you're acquiring a company or or being acquired by a company. And it sounds like what you're saying is that yes, you want a like-minded culture. Uh, you you want, you know, people that uh that you know both companies can kind of see eye to eye, but it's not necessarily an identical culture. You want you want to obviously grow, you want to benefit from aspects of one company's culture that maybe you know don't exist or or could or could be built up, you know, at the other company. Is that is that what you're saying? It's not necessarily looking for identical cultures, but looking for uh synergies, more or less.

Neil McFarlane 10:40

Yeah, and and common themes, right? Okay. If yeah, I give you maybe just an example. Uh when when we were thinking about the anime uh acquisition, uh there was a common theme there of we our goal at and at that time in the transplantation setting and in the hematologic uh uh poetic hematopoietic stem cell transplant business, you know, we were doing great with uh T cell depletion. We were doing great in a lot of the medicines that we were bringing to patients to help transform the transplantation process. But there was also an opportunity for us to be able to think about how you can actually uh pivot and actually have the cells in the peripheral blood then come up and allow you to be able to then do transplants, maybe less invasively, because you don't have to take bone marrow out now. You can actually do it through phoresis and you can drive those things. Well, that's a that's a number one, I thought it was it was a great synergy in terms of uh bringing companies together. But that company was also made up of incredibly dedicated scientists that were uh uh uh incredibly you know uh agile. They were coming with failures. And in our business, as you know, a lot of what we do is managing failure because it is not easy what we do in the bio. Absolutely, yeah. Uh and uh and they had an ethos and just a uh a common bond with what I think we were doing at the time, also, which was uh trying to make sure that that agility then lent itself into bringing new therapeutics to to patients moving forward. So similar uh in terms of mission and culture, but uh not the same for sure.

M&A Lessons: Culture And Synergy

Ben Comer 12:17

Well, um staying with Zevra, I want to find out first how you got there, what circumstances uh led you to to Zevra Therapeutics.

Neil McFarlane 12:26

Uh it's a really good question. So uh if you recall, as you mentioned, that uh after the Adamas um transaction took place, uh that I I was I spent some time on board of a couple of different companies and uh took some time off to kind of recharge and focus to find out uh do you do this again? Much against the advice of most of my friends who have been CEOs, and they said, There's no way you should do this again, Neil. Uh uh and I spent time with my family and and recharged and and quite frankly came back to the same thing. What I love to do is just this. Uh I love to be able to take very challenging uh problems. I love to be able to put really talented people together uh that uh have a common threat most of the times that is the ability to make a really great impact to people uh um uh with our medicines that we can create. And and at the end of the day, put folks together that uh can run through walls and allow us to be able to achieve things that most people don't think is possible. Zevra was one of those. It was a transformation from its prior world and to uh becoming a biotech rare disease company and uh and a board that was behind it and allowed us to be able to actually allow me to be able to say, I think I can actually um uh come here and win uh with the people that were here. Whether we were successful or not, uh that was to be determined. But uh we could absolutely put people around the table, around a common mission, and and try to achieve uh the impossible.

Ben Comer 14:01

Absolutely. Well, what just what about just how you identified Zevra, like how they entered your you know, radar and and how you initially got connected in with you know their their board and former leadership?

Neil McFarlane 14:14

Yeah, I I um first was actually approached about being on the board of the company. Uh and then at that time I was on a couple of other boards and didn't think that it was the right time for me to expand boards. I was I was starting to come up for air and say, well, maybe uh my wife will allow me to become a CEO again, and uh my family will say, Okay, dad, uh go for it. Um so that happened uh not at that time, it happened after the uh I had uh you know passed on the board opportunity. Uh, but I was very impressed with the board uh and what they were trying to accomplish at that time. Uh they wanted to pivot an organization that uh had success in its previous life, but wanted to move forward in a way that could catapult it into becoming a rare disease company. Uh they actually also had uh, we may get into this a little more, but they also had done a bunch of diligence on trying to become a commercial organization uh through the acquisition of Acer therapeutics. Uh I in my past life had seen all of the assets that uh you know ended up becoming Zevra. Uh I knew the the Orphazyme uh uh assets, I knew the solid science and the dedication that had gone into that and had some challenges for sure. But um uh I'd also seen a number of the folks throughout the Acer organization uh through the ups and downs of biotech actually uh you know get a product across the line and and do it with with discipline and and uh and created a commercial organization. So what I what I felt at that time was the pieces, the building blocks of of creating a leading rare disease company uh was being demonstrated by the board and by by all uh the uh you know off the backs of a lot of people, both with Acer's management teams, Orphazyme's management teams, chem farms management teams, and decades of work, that there were enough pieces of the pie here that we could focus on doing a few things well, uh and and then earn the right to go do something else. Uh and it would, yeah, you know, it's not gonna be easy, but if we did that, then we'd be able to take care of patients uh with a huge impact and and actually set ourselves up to be able to become a partner of choice to do this again and again. And we're we're we're on that journey. Uh we're not there yet, but we're on that journey, and and I'd love to be able to talk more about how uh we've been doing along that journey and what our future looks

Why Neil Joined Zevra

Neil McFarlane 16:37

like.

Ben Comer 16:37

Yeah, we we'll definitely get into some uh various aspects of Zevra, uh uh of building a commercial organization is one that I know that uh the audience will be interested in hearing about, you know, your approach to that and how you did it. Um I want to just maybe follow up quickly on the Zevra rebrand and uh pivot to rare diseases. The Orphazyme acquisition happened in uh, I believe May of 2022. Uh you joined the company, as I mentioned, as CEO in in 2023. What was your mindset uh coming into a company that had maybe just kind of started you know this pivot and rebrand? You know, how do you come in and just sort of pick up the reins and go?

Neil McFarlane 17:21

Uh I I it's a it's super we could spend an entire hour just on this topic. Uh what one of the things that I think is critical is focus, and and I I mentioned this before, uh, and looking at what the largest the ability for the organization to create the largest um value was around filing the NDA for NPC. Uh having looked through the science, looked through the data, the work that uh the previous teams had done to be able to start to answer some of the questions from the CRL. Uh uh the the the back end of this was that there was a product here uh and a medicine that made an impact in the lives of NPC patients. Hands down. Huge unmet need, absolutely. Hands down. Now, how do we make sure that we utilize our data, utilize our the processes that are available to us through the the regulators, through the the advocacy organizations, through uh, you know, the the business community to be able to then put those pieces together to take it one step at a time and earn the right to go do something else or earn the right to actually commercialize it. So my my goal coming in was the first thing that we had to do was stop the distraction on anything else that we were doing that wasn't going to be making an impact, to being able to refocus that into how do we get an NDA filed. Uh, we were able to do that. Uh, and then I think the team that was here, and through the collective experience of a lot of people, uh, we were able to then bring in some experts, utilize some insert inside experts, uh, and file that NDA. And then once we file that NDA, which was no small feat, I'm talking over 500,000 pages of documents, uh, you know, uh the vast amount of data that had been collected over years, uh, but enough to be able to answer the questions of the CRL uh and then also build on the robustness of the data set that we had been collecting over time to be able to show not only have we answered the questions, but we've actually also shown unequivocally that we make an impact in the lives of patients with a devastating disease. Uh and we'll talk a little bit more, hopefully later on, about rare disease and the uniqueness of small numbers and just the law of small numbers that that come come with some challenges. But the agencies, both the FDA and EMA, give you some opportunities to be able and flexibility to be able to answer some questions, but it's not always that easy. So that was key. Focus on on meme and pick C and what we could do, because that could be our catapult to then doing things in addition to what we were uh currently uh uh focused on.

Ben Comer 19:59

Right. And I I think the vast majority of the audience will know uh what Neil is talking about when he says uh CRL, but it's a complete response letter. And this was a you know a challenge that um that's ever had to overcome, the the drugs now in the market. So they, you know, they they succeeded. Uh and we'll we will talk a little bit more about that, but um staying with the the rebrand and transition uh for just a

Filing The Niemann-Picks Type C NDA

Ben Comer 20:21

second. Um the the company I believe was previously headquartered in Celebration, Florida. Um it's now I think been moved to Boston, Massachusetts. Can you talk about some of the reasons uh for doing that?

Neil McFarlane 20:35

Yeah, I uh important uh distinction there. We our corporate headquarters on our 10 Q and the corpor in where I where I am and what we've been building is is now in Boston. But we still have an office in Celebration, Florida. We also have an office still in Europe, uh in Denmark, in Copenhagen. Uh but what we have done is kind of started to consolidate our efforts uh and and the new hires that we're making to be able to tap into the biotech ecosystem. But why? Uh let me answer that question because I think it's really important. And it has to do with the fact that a few years ago, 2023, when I got started, we started to work on a strategic plan to create a leading rare disease company. And part of that plan, we had short, medium, and long-term goals. We had to understand what are those pillars that are gonna be core to us being able to grow. So we put, you know, four pillars together around marketed products, our pipeline and innovation. What are the people and the talent and the culture that we need? And then what's the corporate foundation under all of that that allows us to invest in the short, medium, and long term? Because those things that we do in the short term are going to have to be able to lead to long term growth. And part of that was if we are going to become a commercial uh rare disease company at initially at a US level and the potential to grow through geographic expansion into a global company, what sets us up for success to tap? To an ecosystem that has commercial talent, that has late-stage development talent. And we did a study, and that study was looking at other areas. And if you recall, Adamas was based in the Bay Area. I actually lived in the Bay Area before this. So uh, you know, it was also going to be where am I going to be moving to? Uh, am I staying in the Bay Area? Am I going to go back to San Diego? Are we going to go to you know, New Jersey, uh, air, you know, New York area, uh, or even Texas that's that's up and coming. The opportunity, the opportunity said that, and what and this this exercise we did said that if we want to create uh a commercial rare disease biotech company and we want access to X amount of talent, Boston was where you wanted to go and start to create some roots to tap into that system. So that decision was made a few years before, but it's been part of our strategic plan as we now continue to move uh towards becoming that leading rare disease company.

Ben Comer 22:55

Uh

Why Build The Hub In Boston

Ben Comer 22:56

another piece uh of Zevra's um I guess transition or evolution is the acquisition of Acer therapeutics. You you mentioned it previously. I I believe, correct me if I'm wrong, Neil, I think that happened pretty soon after you became CEO. Um what could you say about the fit of that acquisition? I mean, does it speak to what we were talking about before, you know, about culture, about some things that Acer had that you you felt you know would help take Zevra to the next level? Um, you know, what what were the things about Acer that that you wanted to bring into Zevra?

Neil McFarlane 23:32

Yeah, a really, really good question. And your your timing is right. Uh actually, the the transaction was announced before I got here and before I even took the role.

Ben Comer 23:41

Oh, it was, okay.

Neil McFarlane 23:42

And and when I took the role, uh, then it closed shortly thereafter, and then I integrated it. But I did know about it as part of the onboarding process, and and and it made a lot of sense. Creating a rare disease, a high-touch, white glove type of uh service orientation to being able to handle and manage a you know a disease with a prevalence in the United States of about 900 patients, and uh, from a European perspective, about 1,100 patients, you got to have something that's pretty fit for purpose. Uh and the and the board and the management team at the time said this was an opportunity to accelerate and almost catapult the organization, leveraging the contracts that were already there, leveraging especially pharmacy that was there, leveraging uh uh you know, some of the advocacy relationships that were there. All of those things take time to build. And with an NDA on the horizon, uh with uh arimoclomol, now Miplyffa in the United States, uh, it made a lot of sense to me while I was in the process that a small transaction that would allow the organization to start to morph and leverage some foundation, uh commercial foundation that was there. It wasn't all there, but you know, a lot of the bones were there that you could build off of. And some things were great. Uh, and six months into the transition, we said this is not going to be fit for purpose for us to be able to do Miplyffa , but it was gonna be okay for Olpruva. So we learned a lot and we continue to learn through that process and refine our um uh commercialization strategy in the US to identify more patients earlier, to service them with uh as as white glove service as we can legally and compliantly do. I mean, if we're up to me, we'd give even more to patients to try and help them through the system, but we have to do that obviously in a in a in a compliant way. Uh and and uh and that allowed us to be able to then say six months later, after our NDA and after the closing of the deal, we were in an AdCom, and three months after that, we were commercializing a product. Uh so it was it was um uh a very key decision that the board and the management team made previously as part of onboarding. And I felt very strongly that uh building that from scratch never goes well. Uh uh when you're in the middle of uh NDA and you're in the middle of all the other things. It w it could have gone south very quickly. So all in all, we learned and and it was a smart acquisition.

Acer Therapeutics Deal And Celiprolol

Ben Comer 26:06

Yeah, it gets back to your point you made earlier on on focus. Um and you mentioned Olpruva, and there's also celiprolol, which I think is a um a development candidate not approved. Are there other assets or capabilities? You also mentioned um some kind of uh basic uh commercial structure that existed. Was there was there manufacturing uh as well, or were there any other capabilities that that came in through the Acer acquisition?

Neil McFarlane 26:34

Yeah, well, well said. And I think it's important that what I was discussing was around the commercialization. Uh, there were a number of other assets and talk about limiting distractions. There were there were assets that we actually deprioritized. There were assets that we actually then reverted back to the uh original originator of. Um there were there were indications that the products was going after that at the time, after consideration and and looking at the market and the opportunities, didn't make any sense for us to continue to move forward with. So, and that was on the Acer side. That was also on the chem farm side. We had a treasure trove of assets that had been developed and shelved or not shelved, and we started, and we and we've done this now, you know, divesting some of these that are just not things that we're gonna work on. Uh uh and uh and getting some of the intellectual property in the hands of folks who can then continue to build on those and we can get the back end, much like the transaction that we did uh about a month ago, uh, and and divesting the SDX portfolio uh and monetizing the royalties that we were getting on that Azstarys and SDX portfolio uh made a lot of sense to for us to be able to exit that for $50 million, limits our distractions, uh, allows us to be able to focus on becoming an ultra-rare disease company moving forward versus uh, you know, uh some of the, well, some of the other areas that we were focused on. At one time we were doing a sleep study, as one time we were doing um uh focusing in other areas, just didn't make sense for us as we've refined our business model moving forward. So uh uh for us, it was a time to start the the calling of things that were distracting for us and and monetizing them, but it was also a time for us to leverage some of those manufacturing skills, supply chain management and things that were there, also uh to do the business plan uh and understand what is a development plan for celiprolol. We made a call after about a year of doing work. Is there a market? Is there an unmet need? Are patients there? We found all of those things were there, and we made a determination to be able to restart that study, uh, start to enroll celiprolol patients and invest in accelerating that trial. But on the same token, going back to that uh that FDA and talking about the regulators, going back uh and starting to have conversations about ways to accelerate the clinical development of this program for patients, um, uh, as we've now learned a lot more in a year of enrolling patients and data that continues to be generated in the Vascular Ehlers-Danlos syndrome space.

Building A Fit For Purpose Commercial Team

Ben Comer 29:06

Um, I want to talk uh now about building out the commercial organization. Um what could you say about that, Neil? Uh obviously, you know, you you've talked about um Miplyffa, which is your commercial drug uh for Niemann Pick. Uh it was approved, it's it's on the market, it's doing very well. Um and I also take what you said, you know, about you know, this this focus and needing to divest because a a rare disease commercial organization is very different, you know, from a you know primary care uh commercial organization, for example, or or for really any therapeutic area that has a huge number of prescribing physicians. But what what can you say about your approach to to building out that commercial organization uh to support the launch of a you know a drug that that was approved pretty not not too long after you came on board?

Neil McFarlane 30:01

Yeah, if anybody on our team listens to this, they're gonna say, oh my God, here he goes again. Uh uh but but but it's it's it's really about being fit for purpose. Uh any every United States or European launch comes with all of the same requirements for a hypertension drug as an ultra-rare disease product. And uh and when we think about some of those distinctions, it's a lot of uh making sure that you're focused on learning about one patient at a time, understanding the journey of every patient, uh how they work through the system to how they're diagnosed, to how they uh um uh uh uh manage a very challenging, heterogeneous symptomatology, managing multiple specialties, and then ultimately getting therapy, and then making sure that you're able to continue to support them through patient services and the reimbursement challenges that you have, uh, and then all the way through to making sure that if the product is working for them, that you actually make it uh uh that persistency and the things that you can do to lower the barriers uh and educate on new data and new ways to support the patients. So the the fundamentals are no different than anything else you have to do. How you develop a fit-for-purpose organization, how you're investing in the things that are gonna be meaningful to uh the ultra-rare patient organization, uh, how you're gonna be investing in the patient services that are ultra-orphan, uh, hand holding patients through very challenging payer um uh landscape, uh, especially as we grow. And this is not just in the United States, this is in Europe, this is also through compassionate use programs. Uh so for us, in what we do around um uh uh you know, patient first, we talk about our val our values and our mission, and and we talk about redefining uh what's possible uh in bringing life-changing therapies to patients living with rare diseases. That redefining word is critical in what you do because you can't do everything the same because a model wouldn't work. So we we really focus heavily on the centers of excellence in the United States that are where the majority of patients will then end up going to get that treatment plan. In in Europe, uh, you know, we'll be looking at the reference centers in every country uh and how to be able to understand where those rare disease patients are going to get that diagnosis and and also um uh their treatment plans, and then uh how we then put all that together and investing in the things that are driving the future for the patient's uh best outcomes.

Advocacy Partnerships And Patient Support

Ben Comer 32:40

I uh I I I want to ask you a follow-up on patient advocacy groups. They're uh obviously important generally, but extremely important, I think, uh, when you're talking about rare diseases and rare disease patient advocacy groups, um, they they're really important to the success of a launch, I think it's fair to say. Um what what could you say, Neil, about you know, engaging rare disease groups uh at Zevra? Was that something that you had to learn coming into the company? Had you worked on rare diseases, I guess, before this experience and were kind of familiar with the the advocacy landscape. Um, but but I I guess I'm most curious about just how to like engage these groups the right way so that you know it's a give and take and you're getting insights in that are gonna improve the product. And and also, you know, you're you're doing things that that the advocacy group uh wants to support.

Neil McFarlane 33:35

Yeah, I I I think this is where the opportunity to have spent so much time in the clinic uh in the in the transplant setting uh early in my career and uh understanding how important patient advocacy is across all the disciplines, whether it be kidney transplantation to heart transplantation, to all of the organizations uh that then support patients through this journey. Uh, it is critical. Uh it's a force multiplier in any uh uh commercial or or even clinical stage or early stage uh rare disease company. Uh it's great if you can start super early because a lot of times patient advocacy organizations are what then start the drive towards even finding uh and identifying therapies for patients. It doesn't start usually with a therapy and then you find a support organization. It it's it's a family, it's a group that's been touched by a rare disease, and they have the same passion that the the companies have in order to be able to fight for patients and and and families that are dealing with these throughout the journey uh and all the way through to getting them a medicine that can help the and impact their lives. So patient advocacy is critical. Um that collective passion is is is super important. Uh it's not something that I that I think we as an in rare disease learned uh at one time. You start your career with it uh and and you continue to drive through it. So we we we do do that here. Uh we think it's a critical component to partner with rare disease organizations, uh, not just through launch, as you were mentioning earlier, but prior to launch and then through the journey. Because as we identify new patients, they might not even know that that a patient advocacy organization exists for Niemann Pick Disease Type C. Uh as an example, we we had recently a patient who was uh misdiagnosed with multiple sclerosis for decades. Uh they progressed and and and and because of the varying symptoms of Niemann Pick C, they can be buried in other um uh diseases for a long period of time. Uh and this patient got a genetic testing and ended up being being tested for Niemann Pick, but had no idea throughout all these years that a patient organization existed. And we were helpful to be able to say, here are uh uh patient organizations that might be able to help you with the tools and support services to help understand how you're gonna manage with this disease as an adult, number one, but number two, as somebody who had been misdiagnosed for decades. So um we see that partnership as critical. Uh and there are things that um uh uh we think uh can only be done through advocacy and and not through us.

Ben Comer 36:16

Yeah, and you you talked about um support and some hand holding that's needed with uh with rare disease patients. I wonder if you could talk about um, you know, what maybe give some examples of that kind of support. And uh, you know, just in terms of beyond delivering a drug to a patient, um, are there other things that that Zevra does uh for for the rare disease community? Maybe Niemann Pick Type C is an example.

Neil McFarlane 36:41

Yeah. Um and I think it's more than just Niemann Pick C. We we we believe strongly in patient service, we call it patient services, and it it's it it's supporting um all of our uh products that are commercial in the US uh through what we call Amplify Assist. And that's that's the ability to invest in services that allow to help patients through the journey of reimbursement, uh uh supporting through field reimbursement representation and physician offices that may never have been able to work in high-value therapeutics uh and specialty therapeutics. Uh, you know, going to CVS is not what you do when you're working through uh uh the rare disease world. You're gonna have to work through, you know, specialty pharmacies and you're gonna have to work through the uh the varying uh medical exceptions and so on and so forth. So we provide services to physicians to help them, and we also provide services to patients where we can to be able to help them navigate uh the process. But it's white glove service is what we aim to do. And I would even say that that's not unique to us. I think it's unique to all rare diseases. It's a cost of doing business today that you have to be able to have a high-touch, high-impact white glove service that you provide to patients in order to help them through this process. So that's one area. Our Amplify Sys program is very important. Some of the other things that we do, pre-approval uh uh uh is is important. We have a global expanded access program today, uh, where as we're looking at uh our geographic expansion, we currently have a marketing authorization application ongoing in the US. That's very, I'm sorry, in Europe, very similar to that of in the US through the FDA and getting that process through. Uh, we're in the midst of that today, uh, but but prior to that, we're supporting and continuing to have patients come into a either compassionate use or what's known as name patient basis program, where they can actually get pre-uh commercial um uh approved products or pre-approval products to their markets at a patient-by-patient level. So that's another area where we believe very strongly that we also have to do that with a disciplined approach. We'd love to be able to do that for everybody, but we have to be disciplined in how we do it so that way we can expand access to as many patients as possible in the future.

Expanded Access And Europe Readiness

Ben Comer 38:59

Yeah, and I want to ask you about commercializing in Europe and and you know what your plans are there, maybe how it's different from commercializing a rare disease drug in the US. But before I do, you know, you you talked about diagnosis, which is um is such a critical kind of first hurdle for rare disease patients. I've I've heard from a number of leaders, you know, over the years who who talk about that that diagnostic journey and how often it just isn't right on the first time. And it's understandable why. You have you know, people, community physicians who have maybe have never seen an instance of that disease in their entire professional career, and then you get someone in the door um, you know, presenting a certain set of symptoms, and and you, you know, you don't you don't get it right the first time for whatever reason. But you know, you talked about someone receiving a cystic fibrosis diagnosis, uh, which they initially realized was Niemann Pick through uh a genetic test. I saw in uh in Zevra's first quarter earnings report that the company is using a custom AI-driven targeting model and genetic testing collaborations to identify these MPC patients outside of traditional centers of excellence. Um, could you uh just maybe take a minute or two to explain how that works and you know what you do once you find these patients?

Neil McFarlane 40:20

Yeah, just just by the way, before we uh before I get into that, this the patient that I was discussing before, multiple sclerosis.

Ben Comer 40:26

Oh, I'm sorry, not cystic fibrosis. Yeah, yeah.

Neil McFarlane 40:29

Uh which is what I but which, by the way, is a great segue into what we're gonna discuss. Uh, if you think about the symptomatology of multiple sclerosis, there's a motor movement component of it uh and a neurological component of it. And a lot of times with these ultra-rare diseases, you have an impact in the Niemann-Pick C space through the transporter that goes for shuttling cholesterol in and out of the lysosome. That Niemann Pick enzyme uh or the gene that that codes the enzyme that gets it back and forth uh is not working very well. So you get buildup of cholesterol in the lysosome, and eventually the cells die. Well, if the cells die in your brain, you can have everything from cataplexy uh to speech disorders to uh uh swallowing challenges to uh your first symptomatology could be a psychotic break when you're 30 years old. Uh others might be hepatosplenomegaly, uh, an enlarged spleen and liver in a child uh and failure to thrive. So when you think of so many different potential symptoms when you take your loved one to the doctor, uh it sometimes can be very challenging to get that diagnosis. One of the things that is is a benefit is that there has been a product approved in Europe that is now in in uh it's called miglustat. It is in our label to use in combination, Miplyffa and miglustat used in combination, which we can talk about a little bit, but we just had these new treatment guidelines come out from the leading experts across the world talking about how to help to treat Niemann -Pick C. And they say multi, you you know, utilizing multi uh uh treatment approaches uh to being able to uh use as many MOAs or mechanisms of action as possible to be able to help in this uh heterogeneous disease impact the varying areas. So for us, there was a thing called the uh suspicion index that was created.

Using AI To Find Undiagnosed NPC Patients

Neil McFarlane 42:22

You could have all of these symptoms uh and it would be suspicion of Niemann Pick disease type C. Uh it came out a well over a decade ago. Well, we've utilized that suspicion index of varying symptoms, uh, then we've utilized that with uh EMR data, electronic health records, uh, in addition to claims level data records of patients who have potentially been diagnosed with MS, but yet they have a suspicion index of XOI, and uh they've got an EMR record that looks like ABC. Uh and we've put all of this into AI models that allow us to be able to then say, you have the potential, in addition to the centers of excellence that we go to, where patients go to, and that's kind of where you're gonna get your diagnosis, but what about key areas in the United States that have uh a suspicion index overlaid with EMR, overlaid with uh um payer records that say you might have a group of patients at that doctor that that doctor doesn't even know what Niemann Pick disease type C is. So going into that physician's office and educating that physician on Niemann Pick C allows you to have a higher likelihood that there is a Niemann-Pick disease patient that they're treating that don't even know. That's where we see this bespoke model uh being able to be utilized with our and and learn, by the way. We're learning it every day. We're seeing new patients that are on the journey and we learn new things and put into the model. Then it it turns out, well, you should go here and try to educate physicians here, uh, or you should do disease state awareness campaigns there, or so. On and so forth. So really fit for purpose, uh detailed, uh, that I can't even explain to you all of the the modeling that they do. Uh but I've given it to you in the best approach that I could give it to you, which is uh uh uh how it's been explained to me and how they've said I should talk about it uh externally.

Europe Commercial Options And Label Strategy

Ben Comer 44:18

That's uh that's really that's really interesting. Uh makes uh makes a lot of sense. Um I I mentioned uh you will actually you you mentioned the MAA that's been filed uh in in Europe for arimoclomol. I'm gonna I'm not saying that right. I'm just gonna stop trying. Okay. Thank you. Thank you. Um You know, you you uh at both Genzyme and UCB worked in global markets. Um what you know, what do you think is different about uh commercializing a product in Europe versus the US, uh or a rare disease drug that is? And is that something that the company plans to do itself or or or partner?

Neil McFarlane 44:59

Well, I think that the biggest and most important thing you could do is collect data and understand what the appropri what the varying strategies you can go after are. That's what we have done so far for Europe uh and for the rest of markets. We we've actually gone back and understood the market, understood where the patients are. If you recall, I mentioned that there was a product approved in Europe for well over a decade. I believe it was in the early 2000s or mid-2000s when uh miglustat was approved for Niemann Pick in Europe. So a lot of the disease state awareness, a lot of the reference centers in each of the countries uh that service rare disease patients and families and get their ultra diagnosis, that 1,100 patients across Europe have a lot more diagnosed patients than that what we see in the US, uh, where there are 900, you know, prevalent number of patients in the US, but we only know of about 300 or 350 of them that have been diagnosed with Niemann Pick, have an ICD nine or 10 code, and uh and we're working through getting those patients the opportunity and educating physicians around Miplyffa. In Europe, it's much more mature and the market is more mature. So we've done a lot of work to be able to understand what that market looks like, where the lead markets are, what the potential uh pricing ramifications are in each of the markets in Europe, because every market in Europe is its own market, uh, and the sequencing of how you might actually go to market in Europe. We've done all that work. There's one thing though that has to actually then uh inform the future, and that's around the final label. What is your ultimate label gonna look like as your value proposition in Europe uh for each of those markets is gonna dictate size of the market and value. Some have health technology assessments, some have other ways, budget impact models, some have other ways to do that. But for us, we've done the homework. Now we're in the regulatory process to inform and and request what our what you know what the best label is that we can do. And that that that process will then inform do we go to market on our own? Because we have now over 100 patients in our expanded access program, which is a huge impact in Europe. Uh yeah. We don't talk about where the patients are, individual markets, but even if you have 1,100, you're well over, you know, in the 10% plus range. And in certain markets, you might be in the 30, 40% range. So we're doing a good job. And there's it also shows there's a great pull for the product uh from those markets, which we want to be able to make sure we service if we do it on our own very well with that white glove high touch uh that I discussed. Or uh, you know, do we go to a multinational partner party that can service and broaden patient access faster? And and from a financial and fiduciary responsibility, we then have the ability to take that and reinvest in doing it again and again and again. So somewhere between those pillars, going at it ourselves, uh, or the uh, you know, the the multinational uh approach, uh, there's also hybrid approaches in between. We've done the homework to inform that. Now we have to get through the regulatory uh in informed by the regulatory outcomes in order to figure out how we're gonna make that determination moving forward.

Ben Comer 48:07

Okay, so you'll make a final decision once you find out what what the label says.

Neil McFarlane 48:11

Yeah, that's right.

Ben Comer 48:13

Got it. Okay.

FDA And EMA Consistency Challenges

Ben Comer 48:14

Um I want to ask about the FDA. Uh there's uh there's you know, so been some uh some turnover. We lost uh uh Commissioner Martin Makary uh just a couple of days ago. There's been criticism um over several rare disease drug decisions at FDA this year in 2026. Um are you concerned, Neil, about the FDA decision-making process in the rare disease category? And um and maybe just as a follow-on, if there if you have any any color you can share about your experiences uh with uh with the FDA.

Neil McFarlane 48:51

Yeah, I I think I would actually even raise this up to just regulators in general. We're we're working through some of the very similar summer, and I wouldn't even call them challenges, but similar nuances of the FDA as well as the EMA. Uh there's regulatory frameworks and and in in all across both continents that are there to be able to bring safe and effective products to patients. Uh for us, uh in and in ultra-rare disease, those frameworks are for the masses. Uh now there is there's sufficient regulatory flexibility made into those frameworks to be able to manage and get all the great uh rare disease products approved for patients that we see in the US and in Europe. Uh but but the consistency on how those rules are applied is probably one of the biggest challenges that we see as a manufacturer. Because uh one product can be approved and you say, wow, okay, the data is great. Uh the other product you can say, wow, the data's not that great, but yet it the impact the patients is gonna be seen over time in the future. And I think that that consistency of applying the framework is one of the biggest challenges when you don't know the conversations you had going into a regulator if it's what you're gonna get getting out of a regulator. So uh when you get through the the review process. So for for us, we have uh you know had the privilege of going through a very strenuous advisory committee, a CRL, uh, all of the challenges that you can put up to getting a product approved. We went through uh and and and coming out on top. Similarly, in in Europe, you know, we're coming off of an opinion uh that was previous to the FDA CRL in Europe. We're working through that with a more robust package of data, but we're also now working uh uh with more maturity, more real-world evidence, more patients who have been on it. And and we've seen collaborative natures between both the FDA and the EMA around trying to help move us through not just uh uh Niemann-Pick disease type C, but also with celiprolol, we've had informative and and and and responsive uh discussions with the agency. But now we have to go back and have additional discussions around what's going to be uh satisfying to try and accelerate the development of celiprolol, likewise in Europe. So for me, um the flexibility is there, the framework is there, how it's applied is very challenging for us, and and we're trying to work through both the framework and the flexibility to try and make sure this passion we have to bring products to patients living with rare diseases is uh uh uh we're fighting with the advocacy organizations, with the physicians, with the, you know, we're galvanizing everybody to try and run through walls for uh for patients.

Near Term Priorities And Pipeline Strategy

Ben Comer 51:28

Excellent. Well, we are uh running short on time, Neil, but uh before I let you go, I want to hear about your top priorities. I suspect uh the MAA in in Europe has got to be up there, but uh what else could you say about your top priorities for uh for the rest of this year for the company?

Neil McFarlane 51:44

Yeah, we are we're we're fortunate in that uh there are just a few things that we need to do. We're focused on the United States and the continued launch of our Miplyffa asset here. We're just a year in the launch uh and uh at a at 170 uh patients' uh enrollment forms, we feel like we're we're really making some solid traction early in the launch. Uh, but the U.S. launch has got to continue to be a focus for us. The next is our geographic expansion. How are we looking at our marketing authorization application, making sure we're putting every step and foot forward with the robust package that we have? Now with the clinical guidelines that that uh that are here, we feel even more uh reinforcements uh behind us uh with the key opinion leaders pushing. And then it's around celiprolol. What can we do to accelerate that development program for celiprolol for patients in the United States? Uh again, another, you know, we spent a lot of time on Niemann Pick disease type C, but Vascular Ehlers-Danlos Syndrome is another devastating disease without any therapies approved in the United States. And we'd like to be able to find a way to get one uh uh that's safe and effective to the community as fast as possible.

Ben Comer 52:52

Well, uh I'm gonna just sneak one more question in here before uh before we go, Neil. Um, you know, one of the great things about being a commercial organization is you have commercial revenues uh coming in. And I'm curious uh about the way you're thinking about Zevra's pipeline for the future. Is uh do you and maybe you haven't decided yet, but is it is you know, do you plan to acquire or end license new development candidates uh in in the short term? Are you doing you know discovery work internally? What you know, how do you think about that?

Neil McFarlane 53:24

Yeah, it's a great question. We we I would consider ourselves to be a late-stage development and commercial organization today.

Ben Comer 53:31

Okay.

Neil McFarlane 53:32

Uh and and when I when I think about how strategic plans are are put together, you have to find ways to leverage what you're good at. Uh and for us today, executing on my ply for US and the geographic expansion and what we're doing with celiprolol fits really well with what our core capabilities and competencies are. We can find additional ways to leverage what we're building. And I think for us, unlike a lot of traditional rare disease companies that start off with early research and then they get to early clinical, late clinical, and commercial, we're probably going, you know, instead of R to D to C, we're kind of going from C to D to R. So our strategic plan has us being able to execute on what's in front of us, becoming a partner of choice, and then earning the right to go do it again. But it's really gonna go from C to D to R or late D to C to R. Uh we don't have the capacities to do a lot of early state discovery work today. Uh, what I'd like to say though is that if we're gonna become a true leading rare disease company over the next five to ten years, we'll have to have those capabilities internally to be able to continue to innovate for patients living with rare disease.

Closing And Where To Follow

Ben Comer 54:37

Neil, uh, thank you so much for coming on the show and uh and sharing the story of Zevra Therapeutics. I really appreciate it. Thanks, Ben. Appreciate it. We've been speaking with Neil McFarlane, president, CEO, and board director at Zevra Therapeutics. I'm Ben Comer, and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts, and be sure to check out our weekly video casts of these conversations every Monday under the Business of Biotech tab at lifescienceleader.com. We'll see you next week, and thanks as always for listening.