RARE Daily

In Pursuit of a Treatment for His Son, A Lawyer Becomes a Biotech Executive

November 22, 2023

Alex Nemiroff took an unusual path to becoming the general counsel at Praxis Precision Medicines. Nemiroff’s son was diagnosed with a rare genetic epilepsy, and he co-founded the biotechnology company RogCon to develop an antisense oligonucleotide to treat it. Praxis licensed the project and hired Nemiroff as its general counsel. Now, the company has released encouraging data from the first four evaluable patients in a clinical study of the experimental therapy. We spoke to Nemiroff, general counsel at Praxis Precision Medicines, about his journey as a parent of a child with a rare, genetic disease; how he came to launch a biotechnology company to develop a treatment for his son, and what other patient families looking to advance a therapy can learn from his experience.


Daniel Levine: Alex, thanks for joining us.

Alex Nemiroff: Thanks, Danny. Happy to be here.

Daniel Levine: We’re going to talk about a rare and life robbing genetic epilepsy, SCN2A, Praxis Precision Medicines, and its efforts to bring a therapy to patients. Let’s start with how you became involved in this world. When your son Roger was diagnosed with the condition shortly after birth, what happened and how was he diagnosed?

Alex Nemiroff: Yeah, so Roger was born in 2014. He was my first child. My wife prior to his birth felt something in utero, which in retrospect we realized were seizures. So, he was born [and] about seven hours after birth, we were told by the doctors who had taken him away that he had had a seizure. And like I said, it was our first child. I wasn’t really familiar with the process at all. I didn’t really know much about seizures, but it was quite scary and concerning. I remember distinctly, my wife asked, “Is he going to die?” And there was a hesitation in the response of, “We don’t think so, but we don’t know.” So that was of course incredibly scary and concerning for us. He was put into the NICU; he continued to have seizures. They started dosing him on pretty heavy anti-epileptic medication and within a couple of weeks we transferred him from Miami where we live up to Boston. And a few months after that he got the diagnosis of an SCN2A mutation. It’s actually about three months from birth until we got the diagnosis.

Daniel Levine: And at that point, what was understood about the condition and what did doctors tell you?

Alex Nemiroff: There was very little understood. We were told that mutations in SCN2A had not been studied all that much. There were a few isolated cases reported, but there wasn’t all that much known. I remember distinctly that the prognosis was poor, but uncertain largely because, like I said, no one had really studied this in any kind of comprehensive manner.

Daniel Levine: SCN2A-related disorders have effects beyond epilepsy. How do they manifest themselves and progress?

Alex Nemiroff: So, what we know today, obviously from a large body of data, is that seizures are one of many comorbidities in this disease. Certainly, the most apparent; in many cases, the most problematic. Beyond that, most children with this disorder, [the] overwhelming number do not talk. Most do not walk. There’s gastrointestinal issues, there’s sleep issues. Some doctors will tell you there’s a lot of intellectual disability. I personally take a little bit of issue with that, but from an expressive language standpoint, it’s very complex and not all there—a whole just range of symptoms, pretty much any symptom you could think of for a pretty severe disease exists within this one. And then one of the most concerning is something called SUDEP, which is sudden unexpected death in epilepsy and within this disease that’s quite common from some of the data that we’ve looked at recently, we project around 20 percent of kids diagnosed with this disease will die before teenage years.

Daniel Levine: I think one of the things—people who don’t live with someone who has a seizure disorder—they may not understand the frequencies with which they occur, but [also] what happens within a household when an event happens. What’s that like?

Alex Nemiroff: Yeah, so it’s quite concerning and all-encompassing within this disease. For many children, certainly my son falls into this category, they’re happening pretty frequently and so over time you almost get desensitized to them for better or for worse. But what happens is with typical kids or adults that are having seizures where you need to immediately be by the kid’s side, supporting the child, making sure their airways are open, making sure they’re in a safe place. In many cases, you need to administer rescue medication, which is a very potent dose of benzodiazepine these days. It’s administered intranasally and beyond the immediate acute response, the child will thereafter be tired, usually need to sleep. It becomes incredibly disruptive to the day, let alone the risks that are taking place. And frankly, what does not get discussed at all, but I would argue is close to as important, is just the emotional toll that this takes on every one of the family members, the parents, certainly siblings, and everyone else around. You can only imagine not only this happening within a house, but anytime when we do go out and when we bring our son out, this could just happen at any moment. And just what that’s like? It’s incredibly overwhelming.

Daniel Levine: One of the concerns of seizure disorders is that they can cause progressive damage to the brain. What’s known about this?

Alex Nemiroff: So, there’s really limited definitive evidence of reversible versus irreversible damage from seizures, sort of chronic seizures. There’s no question that the more seizures that are happening, the bigger the risk. And it’s not just in the form of potentially reaching a point of irreversibility, but things like what I mentioned, SUDEP, this unexpected death in epilepsy. And so there’s no question when you look at this disease and when we started to look at this disease more from a therapeutic standpoint, you have to focus on seizures first. It’s so important. It’s so important from just a practical day-in day-out standpoint and also just for sort of risk management as it relates to just this awful disease.

Daniel Levine: Well, you mentioned some of the medications that you’ve used, but what treatment options exist today and how responsive is someone with SCN2A to existing therapies?

Alex Nemiroff: So, the treatment options that exist today are for the most part the same treatment options that have existed for 50-plus years with some exceptions, but certainly with minimal exception. As it relates to the efficacy of these treatments, I would argue they do not meet the needs of patients. I think certain patients have better responses to certain medications, but for the most part, patients are not having any sort of prolonged seizure control. There’s patients that like my son, who will respond better for a period of time and then all of a sudden he’ll just have breakthrough seizures that we can’t control using the same medications. The other real challenge with the existing landscape of medications is the awful side effect profile of these drugs. Just to illustrate this, probably the best medication within the SCN2A community consistently right now is phenytoin, Dilantin. This is a medication that was approved, I believe, 70 years ago, 60-70 years ago. The side effect profile is awful, but this medication cannot be dosed within hours of food or you’re really impacting the absorption and the exposure levels. So what we need to do, and this for my son is administered three times a day. He cannot eat for an hour and a half before the medication and an hour after, and he gets the medication three times a day. When you think about the amount of waking hours and then you’re pulling out on both sides, so effectively three hours, more or less, three times a day for a child, the inability to eat any type of food, it becomes incredibly burdensome to do this. And despite all that, we’re not getting consist seizure control. There’s massive fluctuation naturally with this medication. So it’s just very hard to control. We also need to draw his blood very frequently to check his concentration levels of this medication because as it swings up too high, he’s vomiting, he has nystagmus, he’s just incredibly sedated, and when it drops too low, his breakthrough seizures. So it is just an incredibly burdensome landscape.

Daniel Levine: I should note your son’s no longer a little boy. How old is he today and how’s he doing?

Alex Nemiroff: So, he’s nine years old today. I get asked this question a lot from both friends and professionally. I would say relative to the disease progression and just the natural history of this disease, he’s doing well. But that said, he’s still having frequent seizures, a lot of side effects and issues, a ton of comorbidities. He’s nonverbal, sleep disruption. I think he’s doing great because I know how bad this disease is and relative to some of the patients I could say that, but by no means would anybody look at the situation and think he’s doing well, unfortunately.

Daniel Levine: You’re an attorney today, you’re general counsel at Praxis, but you spent most of your career working outside of biopharma. You did co-found a biotech with another SCN2A parent, RogCon to develop a treatment for SCN2A. How did this come about?

Alex Nemiroff: So, when we got the diagnosis and maybe six or so months after, we realized there were no good treatment options for our son. And I realized at the time that unless we drive something towards discovering something new, nothing’s going to happen and no one’s going to do it. There’s a ton of ultra-rare diseases, as you know way better than me, and to get a company or even really leadership at a company to be interested in one, you have to take that upon yourself. I looked back too and I also realized that this was my first child. I wasn’t familiar with what a newborn and what that experience is like. Immediately when we got this diagnosis, I sort of went into this mode of we need to figure something out to treat this, and I’ll use the phrase loosely “fix this.” And if I’m honest, when I look back, I think part of this was my own subconscious maybe fear of actually dealing with and feeling the pain of the situation and what he was going through. But whatever it was, I knew that we had to drive something ourselves. I’ve learned that sometimes doing the right thing for the wrong reasons can ultimately lead you to doing the right thing for the right reasons. And so I think that is what drove me initially. But at the end of the day, we started really contacting any doctor, any scientist, anyone who might have some understanding of what was going on with mutations in this gene. I met another parent early on, as you mentioned, Kelly, who shared a similar focus around, “We’re going to figure this out. This is not a life for our kids or any kid and we’re going to find an alternative option.” And we were just relentless. And we discovered there was a scientist in Australia, Steve Petrou, who had done some early work around this particular gene in epilepsy. We connected with him. And I also realized back then, in order to really be able to drive this in a way that I knew we would need to in a very competitive drug development space, we would have to do this through the route of a company versus a nonprofit foundation in order to really get this prioritized and have a seat at the table. So we were fortunately able to make a commercially viable case for somebody to develop in this disease. The diagnostics were getting better, and you could start to see the shape of an actual community. So, we created a company called RogCon named after my son Roger and her son Connor. And we learned from Steve that at the time we felt that mutations in this gene caused really a gain of function in terms of the biophysical characterization, and there would theoretically be a way to downregulate the mRNA of SCN2A through an antisense oligonucleotide an ASO approach. And there was really only one company back then that was fairly well known for developing these types of drugs, and it was Ionis. And so, we went out there and we pitched them on working with us to discover and then potentially develop a new therapeutic approach for SCN2A. And fortunately, very lucky for us, they agreed.

Daniel Levine: What gave you the confidence you would be able to do this as someone who wasn’t steeped in the industry at the time, and what kind of capital did you think you would need to raise and how have you funded all this work?

Alex Nemiroff: So, it was a bit of being naive about what this would take, because in my mind, there was no alternative to finding a solution for this. And so we were just going to keep going no matter what. And it was incredibly challenging, as you well know, the drug development path. I mean, countless people in positions of power would tell us, go home, take care of your kids. You’re not going to really change the course of this disease. And I think for us, there was just no alternative. And it becomes easy and almost simple when that’s the mindset because you kind of just keep fighting. What becomes very difficult is that in parallel you need to take care of a very sick child, which requires a lot of time focus. And the emotional toll was enormous from a capital standpoint. To develop a drug, of course, requires many tens of millions of dollars. As I looked at the path, what I realized was we just needed to raise enough money to get to a point of demonstrating some degree of proof of concept, and then we would have to partner because the capital requirements were just too large and we didn’t have the built-in expertise to be able to actually develop it. So we raised a little less than $5 million to be able to get this through partnership with Ionis to a proof of concept stage. And then we were at the point of looking to partner on the continued development.

Daniel Levine: You mentioned the partnership with Ionis. There was also a collaboration with the Florey Institute of Neuroscience. What was that relationship and how did it come about?

Alex Nemiroff: One of the first conversations with Steve Petrou, who at the time was the deputy head of the Florey Institute, was really a question of, “Okay, what do we need to do to better understand this disease in contemplation of ultimately being able to treat it?” And he said, “We need to develop model systems to study this disease, essentially animal models, rodent models, stem cell models.” So we engaged him and the Florey Institute to do that work, and they’ve continued to be a partner all the way through to this day.

Daniel Levine: How did the discussions with Praxis come about?

Alex Nemiroff: So, the former CEO of Praxis, he had been at Claris, which is one of the venture capital firms that originally seeded Praxis. And they were looking, as they started the company Praxis, to really go after three different genetic epilepsy targets. They wanted to go after SCN2A as one of the three, but we had actually by that point made some decent inroads with respect to the model systems that we had created and starting conversations with Ionis around possibly an antisense oligonucleotide. So we just decided to stay connected and he was providing some informal mentorship and guidance on really the drug development path. When we got to the point of proof of concept with this ASO and these animal models, we needed to partner because the capital requirements were too big and Ionis had interest in partnering with us, and Praxis had interest in partnering with us. And in kind of looking at what would be the best fit for the program, Praxis really was a genetic epilepsy company. They were committed to developing drugs for genetic epilepsies, and ultimately we decided to do a deal with them.

Daniel Levine: You’re now general counsel of Praxis. How did that come about and what does it mean to be working with a company that’s developing a treatment for a disease that afflicts your son?

Alex Nemiroff: So, it came about because part of any deal we were going to do would, from our standpoint, require that Kelly, Steve, and myself come along with that deal and be a part of the company because we all know well that the programs get shelved constantly. There’s competing priorities and limited capital and resources. So, in order to ensure that this program, this drug, would continue to progress, we needed to actually be sitting at the table. I have a law degree. I practiced for a number of years and there was just a logical fit for me to step in the legal role. And ultimately that progressed to now be general counsel. It’s exciting to be a part of this, developing a treatment for SCN2A disease, knowing it so well. It allows myself and Kelly, as parents of kids with this disease, to provide very unique perspectives on the disease and what it takes. There’s no question that every time there’s a data readout, anytime a challenge arises, and of course we all know there’s many, it is really tough because we’re so close to this disease and a number of the kids. There’s a family with a child who both she and I have been very close with for many years and the kid passed away two days ago and this stuff happens along the way. I think that the best that we try to do is use that as fuel and really kind of paint the picture of how much these families and these kids are all counting on us throughout the company. And we’re doing that constantly.

Daniel Levine: What’s known about the results from studies that have been done to date for the therapy?

Alex Nemiroff: So, we’ve run one clinical study so far with this drug, a first inpatient study. This was designed as a safety study largely really to demonstrate that this molecule was safe. There was some hope internally that we would see some, maybe very small, efficacy. I know externally, I believe, that was shared. And I think there was an analyst who stated that 10 to 15 percent efficacy, just to demonstrate there’s a signal, would be wonderful. We just read out the preliminary data a few weeks ago from that study and it kind of blew us all away. There was a 45 percent median seizure reduction. There was 35 percent increase in the number of seizure-free days. There was no concerning safety issues. So no serious adverse events or treatment emergent adverse events related to the drug. We saw a very clear response after a single dose. It was pretty phenomenal, and it just reaffirmed what we always believed to be true. And I believe to my core that this molecule absolutely impacts this disease.

Daniel Levine: And this is the ASO you were developing at RogCon. What’s known about the way it works?

Alex Nemiroff: So, this is an ASO that downregulates the mRNA in SCN2A. The disease population, which only was really developed in terms of the understanding over time, actually breaks into two big buckets, which is children whose mutations cause this gain of function, and then children whose mutations cause a loss of function. The phenotype, the profile of the patients are very different. This drug, Prax-222, which was formulated RogCon 222, because it’s effectively downregulating, is meant to treat these gain of function patients. And we believe this drug has the potential to be disease modifying just based on the mechanism. So, not only to impact things like seizures, but over time to really change the entire course of the disease.

Daniel Levine: And what’s the development path forward?

Alex Nemiroff: So, our plan now is to take this, the full data from this study along with all of the different preclinical studies that were done, and to bring this to the FDA and really to discuss the path, given the response that we saw in this first study. And of course, given the disease and how awful this disease is, we’re really looking to initiate a global pivotal study in 2024.

Daniel Levine: What advice would you offer other patient families looking to advance the development of therapies for their conditions and any lessons learned from your experiences, particularly with fostering collaborations with both researchers and pharmaceutical developers?

Alex Nemiroff: Yeah, so there’s clearly a bunch of lessons learned along the way, and of course in retrospect, I think like anything in life I could say I would’ve done this versus that. We all know it’s a very challenging path, emotionally, physically, practically speaking. I think if there is a mindset that really there is no alternative, which I think becomes really important as you start to face a lot of the challenges, that’s really the only way to do this. So it becomes a relentlessness around driving something forward in our disease. Nothing was really known. It was sort of starting from scratch. I think as I talked to other families and other diseases, the landscape’s always different. It becomes a matter of seeing a path that you believe is viable and then just going after that relentlessly. And it will change as it did for us at many different time points. But really the commitment is the single most important thing.

Daniel Levine: Alex Nemiroff, general counsel at Praxis Precision Medicines and co-founder of RogCon. Alex, thanks so much for your time today.

Alex Nemiroff: Thanks, Danny. Great to talk to you.

This transcript has been edited for clarity and readability.


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