Developing Treatments for SCN2A

Episode 4: Developing treatments

Taking a treatment from the laboratory in to clinical trials and then to becoming available for use is a complex and expensive process. We talk with Dr Kiran Reddy, President and CEO of Praxis Precision Medicines, about the plans for the RC-222 treatment program with the eventual goal of having a treatment available for SCN2A gain-of-function epilepsies.

Hosted by Kris Pierce and David Cunnington, parents of Will, who has SCN2A.

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Guest interview:

Dr Kiran Reddy is President & CEO of Praxis Precision Medicines, Inc a biotech compay focused on developing new therapies for neurologic and psychiatric disorders. Dr. Reddy serves on the business advisory board of the National Epilepsy Foundation, the board of the New England Epilepsy Foundation, and the Council for the National Center for Translational Sciences within NIH. Dr. Reddy holds MD and MBA degrees from Georgetown University. He completed his internship in medicine and his neurology residency at Harvard/Massachusetts General Hospital. He was previously a Howard Hughes science fellow, and has authored several peer-reviewed scientific papers in the field of epilepsy, neuroimmunology, and neurodegenerative diseases.

Regular Hosts:

Ms Kris Pierce RN MHSc MWellness, is a rare disease advocate and mother to Will who has SCN2A. Kris has held a range of board, project management, advocate and consumer representative roles and has been instrumental in working with local, state and federal governments to secure funding for multi-million dollar projects. Kris is highly skilled in building teams to work together collaboratively and is a co-founder of Genetic Epilepsy Team Australia (GETA) and SCN2A Australia, and a RARE Global Advocacy Leadership Council member.

Follow Kris on LinkedIn or Twitter.

Dr David Cunnington is a sleep physician and father to Will who has SCN2A. He is director of Melbourne Sleep Disorders Centre, and co-founder and contributor to SleepHub. David trained in sleep medicine both in Australia and at Harvard Medical School in the United States. David’s clinical practice covers all areas of sleep medicine and he is actively involved in training health professionals in sleep. David is a regular commentator on sleep, both in traditional and social media.
Follow David’s posts on sleep on Facebook or Twitter


Intro: Welcome to SCN2A Insights bringing you the latest research and clinical updates on SCN2A and genetic epilepsy from around the world.

Kris Pierce: Hi. My name is Kris Pierce.

David Cunnington: And I’m David Cunnington.

Kris Pierce: Welcome to SCN2A Insights. In this episode, we tackle the challenges of making a new treatment a reality by interviewing Dr. Kiran Reddy. Dr. Reddy is the President and CEO of Praxis Precision Medicines.

David Cunnington: So thanks very much for helping us out, Kiran. What does Praxis Precision Medicines do?

Kiran Reddy: Thank you, David, for inviting me to be able to speak to the SCN2A community and I’m very pleased to tell you about Praxis Precision Medicines. We are a small biotech company. We actually have operations in Boston, Massachusetts in the United States. We also have operations in Melbourne, Australia. And we are focused on discovering and developing new medicines for children with genetically defined epileptic encephalopathy, so epilepsy with neuro-developmental disorders. So that is our core focus at Praxis.

David Cunnington: What is Praxis Precision Medicines doing in the SCN2A space?

Kiran Reddy: We are very excited about our efforts in SCN2A that have actually very recently come together. We are looking to develop treatments for SCN2A epileptic encephalopathies that are driven by gain-of-function mutations. So this is increased function of the SCN2A gene or the Nav1.2 channel, over activity of that channel can is linked to developmental epileptic encephalopathies. And we are focused on antisense oligonucleotide treatment for SCN2A gain-of-function mutations.

This is a program that we are working on in collaboration with Ionis Pharmaceuticals that has been a world leader and the expert in developing antisense oligonucleotides. Now, they are most notable for getting a drug approved for spinal muscular atrophy (SMA), which is also antisense oligonucleotide. So we are quite excited to be working with Ionis. We are also working with a small company called RogCon, and RogCon had done some of the early work with Ionis around understanding how an antisense oligonucleotide or an ASO could be useful in treating mouse models of SCN2A gain-of-function epileptic encephalopathy.

So we at Praxis are now going to take on the baton from RogCon and Ionis and we will develop an antisense oligonucleotide in clinical trials and hopefully someday have the ability to have that drug be approved for patients with SCN2A gain-of-function epileptic encephalopathy.

David Cunnington: Yeah, that’s really exciting. And if everything goes to plan and there are no major hurdles, what’s your approximate timeline for phase 3 clinical trials and then regulatory approval and then availability of treatment?

Kiran Reddy: Big question and always one that is at the top of our mind is how quickly can we move and our focus is to move. Right now, the program is doing animal testing and we would love to do as rapidly as possible human testing and through late phase clinical trials as well.

I’m always careful about providing timelines because I don’t want to provide inaccurate timelines. But what I will say is this is – right now, we expect to be rigorously studying our antisense oligonucleotides in animal safety next year. So those will be in monkeys and in other species of animals proving that this antisense oligonucleotide is safe. And once we have done so, then we will meet with the FDA in the United States and potentially other regulatory bodies in the world to come up with a timeline for when we can start clinical trials.

So the timeline for clinical trials would be predicated on the safety data that we generate in animals next year and then presenting that to regulatory agencies. And with that, I would have a much better sense and clarity as to when we could start clinical trials. So I hope to be able to share with you approximately in the next 6 months when we have more clarity around out timelines for starting clinical trials and the potential for timelines for approval.

David Cunnington: Yeah, that’s great. And there are lots of challenges and I don’t need to tell you lots of money that’s needed to drive these drug development processes. What are some of the things that could slow that down or some of the challenges that a company like Praxis faces?

Kiran Reddy: We are often faced with many challenges in trying to discover new medicines. When I think about the major areas where we run into roadblocks, I think of one area being animal models and having good animal models of disease specifically in the area of genetic epilepsies. It’s having good mouse models that we think represent what’s happening in humans reasonably well in terms of seizures and the non-seizure issues that children with SCN2A have.

So having high quality animal models is an important aspect of being able to find new therapies for all genetic epilepsies and certainly absolutely true for SCN2A genetic epilepsies. And I would say I would expand that even beyond animal models. I would even include cellular models. So there is our – you maybe and your community maybe aware of stem cell-derived models. These are where you can take skin cells from a patient and convert them in to neurons in a dish and you can assay and assess and study how well are those neurons working. And those models can be very, very useful as well. So we often in biotech companies struggle with getting good access to high quality models of the whether these animal models or cell-based models.

Another area that we have challenges from a company perspective is we will often get asked by potential investors that we are looking for funding to support developing these new medicines. Well, how many patients are there that have this problem? And often, the motivation for us in the question is that in knowing the number of patients they would have an ability to assess what is the market size. If you are able to get a drug approved, how many patients could benefit from this drug and what would be the overall revenue potential of a drug like that?

So we often will struggle to find good data around patient numbers. That is another area that we certainly could greatly benefit from groups helping us get good and solid epidemiology on the numbers of patients with various genetic epilepsies.

Related to that is once you now have a good handle of the numbers of patients, you also want to understand what is the natural history of the disease in patients with genetic epilepsies? And in SCN2A, a question will come, how severe are the seizure disorders in these children, what are the frequency of seizures depending on age, what are the non-seizure issues that children have from those behavioral learning, memory, motor symptoms, understanding what those non-seizure symptoms are over time and per age group? Those are really critical so that we can design clinical trials the right way. We know what to follow when we give our drug.

The advantage of natural history studies are that in certain contexts and with discussions with regulatory bodies, you might be able to avoid doing placebo-control studies to get a drug approved. So that if you got a good natural history study, you can say, the normal course of a child with SCN2A epileptic encephalopathy gain-of-function mutations is as so at one year, at three years, at five years. This is what would happen to these children and if that’s well-known you can then do a trial only with giving the drug so no placebo control and be able to assess what does the drug do in terms of its effects on seizures, on motor symptoms, on behavior symptoms, on learning and memory, and have some confidence that your drug is doing something better than what the natural history of the disease would be.

These are a few areas that I would highlight as the areas that biotech companies like Praxis often need help to be able to generate those types of information that could really allow us to be successful in finding new medicine.

David Cunnington: It really highlights the importance of getting good natural history study data because potentially that could reduce the cost of drug development and speed up the timeline of drug development which is critical for us in the SCN2A community. And it does give really helpful information. I’ve been involved at a regulatory and reimbursement level here in Australia with new drug approvals and drug development and drugs that come to Australia for regulation with that type of package, it’s much easier to build that pharmacoeconomic argument about who is going to benefit, where we are going to get the most bang for buck, in a government payer system like we have in Australia.

Kiran Reddy: Absolutely. Having really strong datasets not just on the drug is working to treat certain symptoms but understanding the broader context here of how society benefits with the drug that have significant enough effects that these children are leading better lives and that there’s real material effects on overall healthcare outcomes and showing that becomes pretty meaningful in being to have different payers, whether it would be government payers or private players pay for the drug and fundamentally then access to the medicine itself is obviously what we are all looking for.

David Cunnington: What can the patient community do to help companies like Praxis in a drug development program like you’re outlining for SCN2A?

Kiran Reddy: I’ve had the privilege of getting to know families with SCN2A, children with SCN2A, and I fully appreciate how challenging it is just on a day-to-day basis to care for your children. And because of that, I appreciate that is a full-time job in and of itself and to ask for more, it’s a lot to ask for some individuals. But I’ve also been so impressed by the energy and the passion that families with SCN2A that they have and being able to make the time to be able to help companies like Praxis and academic scientists and clinicians working in SCN2A to help them be successful and enable us.

So I think there are a number of ways that we can receive help. It could be as simple as just keeping aware of what’s going on in the community scientifically, clinically so that they could be prepared to be involved in clinical studies when it makes sense. It could be participating in natural history studies, which I think are really critical to finding new medicines and getting them approved for SCN2A. So being able to participate in surveys, in natural history studies around what their child is facing would be really helpful.

And then to the degree that they can garner support for – and help support fundraising for foundations that could support the building of animal models and support even the right set of clinicians, academic centers that will be expert in being able to take care of these children. I mean these are all wonderful things that could really help put the right infrastructure in place so that when a company like Praxis comes to the field of SCN2A, they say, “Wow! Look at all – look at how everything is so nicely set up here.” It makes our life easy and it allows us to spend the money that we raise on developing the medicine and not necessarily on building the infrastructure to develop the medicine.

David Cunnington: Yeah, that’s a really nice point because you are looking at where you might run a clinical trial for example in a couple of years when you’re at that phase. That’s a really attractive proposition if you’ve got an academic researcher, clinicians, patients all with a track record of working together. That’s just a perfect setup to be able to come in and that to be site to be able to run a clinical trial.

Kiran Reddy: Absolutely. And I think one of the things that the SMA community did really well is exactly that. They not only helped put together natural history studies. They also did a nice job of building a coordinated set of expert clinical research groups that then became the logical trial sites for the Ionis antisense oligonucleotide.

David Cunnington: And it highlights the importance for us as a community of working in our own countries within our own clinicians and research centers and starting to liaise with our own regulatory bodies and reimbursers because those issues will be different in different countries.

Kiran Reddy: Absolutely. Acting locally can have very meaningful effects in aggregate. These areas and being able to help support building the infrastructure so that we could study SCN2A and we can study new medicines for SCN2A effectively, this is what’s going to have the most impact in finding new treatments for these children.

David Cunnington: Great. Thanks for that really helpful information, Kiran. And best of luck with Praxis and your efforts to find a treatment for our children.

Kiran Reddy: Thank you again for inviting me to participate and I look forward to being able to provide you and the community updates as we progress this program.

Kris Pierce: That was a really interesting interview. What were your take-home messages from that interview with Kiran?

David Cunnington: Kiran really did a good job of pointing out the importance of natural history study and how better understanding of how SCN2A evolves over time may really help to bring forward treatments even by a number of years compared to if we don’t have that data from a natural history study.

Kris Pierce: One of the other points that Kiran highlighted in the interview was about SCN2A communities developing a nidus in their own country and making sure that they’ve got a patient group, a clinician, and a researcher working towards better treatments and better outcomes for patients. And this will also help each country move towards treatments in a faster way.

Keep up to date with the latest updates by subscribing to this podcast.

David Cunnington: Or get regular updates on SCN2A through SCN2A Australia’s Facebook or Twitter @SCN2AAustralia.

Outro: This podcast is not intended as a substitute for your own independent health professional’s advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider within your country or place of residency with any questions you may have regarding a medical condition.