Hope in Action: Fighting SPG50 and Beyond with Elpida Therapeutics

[MUSIC] In general terms, children are paralyzed in the way used to on by the age of 10. Quadriplegic with age of 20, most of them never learned to walk or talk. And it's a neurodevelopmental neurodegenerative disease. It's very rare. Michael was the only child in Canada. There is about 130 known cases worldwide. So as you can imagine, us treating 28 children by next year, we will have those almost 25 to 30% of the world's population. [MUSIC] Welcome to another episode of Sounds of Science. I'm your host, Mary Parker, and today we're diving into a story of resilience, innovation, and the power of community and rare disease research. So much has happened since we last spoke with today's guest, beginning with a major milestone. Being granted rare pediatric disease designation by the FDA for Melpita, an investigational treatment for spastic paraplegia type 50 or SPG 50. I'm thrilled to welcome back Terry Peravolakis, CEO of Elpita Therapeutics, who last joined us on the podcast in November 2022 to share the deeply personal story of his son Michael and his journey living with SPG 50. Terry, it's good to have you back. >> Yeah, thank you for having me again. I really appreciate it. >> We appreciate your time and your expertise. So can we begin by grounding our listeners in the story behind Elpita Therapeutics and the rare disease at the heart of the journey, SPG 50? >> I'll give you guys the colds notes. So again, going back to our original story, my son was diagnosed with SPG 15, April 2nd, at 2019. We were broken as a family. We found an incredible team. We made a gene therapy for him. We treated two children and we thought we could handle over the license and all the drug. And someone else would take it on and, unfortunately, that was in the case. We formed Elpita Therapeutics. We did a phase one, two in the U.S. We then opened up a capacity use site in Spain. And actually two sites in Spain. And since then, we've treated 10 children with SPG 50 mostly under the age of two. But children ranging from five months old all the way to 17 years old. We then took on two more programs. One was Charlotte Maria Tooth for Jay. We received $5 million from the state of California. We did a natural history study. We made plasma detoxicology and we got approval from the FDA to move forward. With that program last year. And we hope to be in the clinic sometime in January or February. And then our third program, CLN 7, Baden's disease. We finally were able to make the drug product. It'll be ready in January. And we'll be opening up a phase one, two as well for that program. So things are moving along really well. And just add to that a little bit more in December after the peer of Eve one away at the FDA. We started a consulting division at a necessity. And we took on seven more programs through consultancy in order for us to help where conditions get through a 90 filing, a PLA filing, or even just a proof of concept. So we're really, really busy at the appeal of the therapeutics. Yeah, that's a lot of ground to cover in just a few years. So that's pretty impressive. And you catch us up on Michael. How's he doing? What's he been up to? Yeah, Michael's good. You know, I mean, relative to the condition, obviously and relative to where he's at. But he's moving along. He's in school. He's happy and just in progressing with what he's going through. But obviously I didn't cure him. And that's kind of something that I have to live with and kind of get over. But he's doing better than where he would have been if we did that thing. Good. And can you give us just a little bit of a thumbnail sketch of your first time here on the podcast. How was El Pida founded and how did you find Mel Pida? Yeah, absolutely. So we were a soccer tournament in sense of fashion that was funded and was done by Havier Garcia and foundation Columbus. And it turned to Havier and I said, we need to do more. We need to see more children. Do you think we should, you know, you'd help me start this nonprofit? You said, absolutely. We start, forms El Pida therapeutics with Sheila McKill. We moved it forward and that's how we're here today. El Pida was formed by the word hope in Greek. And it was a pun on words with Mel Pida, the drug we made for Michael, which was Michael's hope, Mel Pida. I love that. And for anyone unfamiliar with SPG 50, could you describe the condition and how it impacts children like Michael? Absolutely. So in general terms, children are paralyzed in the way used to them by the age of 10, quadriplegic, but the age of 20, they never, most of them never learned to walk or talk. And how rare is it? It's very rare. So as you can imagine, us treating 28 children by next year, we will have those almost, you know, 25 to 30% of the world's population. Yeah, that's amazing. Obviously access to treatment can be a big issue for something as rare as that. Yeah, we've been very fortunate that we had an amazing partner of our origin who made us extra doses of drug, which we've been able to treat children. But unfortunately that drug will run out in June of next year. And then we have to find a way to make sure that every child receives it after that. Well, speaking of collaborations, can we talk about how collaboration and innovation helped bring Melpita to life? So first, how does it work at the genetic level? So after 20, lacking myself in the room for 24 hours, we realized that we could do either an ASO or gene therapy. We went down the ASO path and because at the time the technology wasn't going to work for our disease and our function, we went down the gene replacement therapy path. We were fortunate enough to meet Dr. Stephen Gray and Dr. St. Shen. They created a mouse. They created a sun line. They proved the vector worked in both. They also did a wild type safety study that showed that it was relatively safe. We then moved to Charles River, who was our partner in toxicology. We did a rat safety study, a GLP safety study there. From then we filed our I&D to the FDA, manufactured the drug at Viragen, treated Michael at sick kids, and then also tumor children at UTSW and Dallas. In your experience, how can partnerships with contract research organizations like Charles River and with Viral Gen accelerate progress in rare disease programs like yours? Honestly, in rare disease programs like mine, partnerships are fundamental. We're not a company. We don't have endless amounts of funds. We don't have the resources to understand the process. We rely on our partners to make sure that they help us understand the process thoroughly. They help us make sure that we are aligned with what the FDA is looking for. They help us align on the price as well because again, we don't have endless funds. These funds come from events and in blood sweat and tears, honestly. These partnerships are fundamental and we're so grateful that Charles River has been an amazing partner of ours. From the very beginning, meeting Lauren Black at an event, meeting the team in Quebec and just seeing that they cared about Michael and these children really made a huge difference in how we move forward. Built on blood sweat and tears. Sometimes literally when you're doing tissue banking. Exactly. Speaking of the regulatory angle, we know that small clinical trials like yours present a lot of unique challenges from getting literally getting to the patients since they're typically spread out all over the world. In light of current public policy environments, how do you envision the approval pathway for these trials evolving? I'll be honest with you. When we started this journey, everybody was like, oh, the regulatory bodies, the worst, they're going to give you a hard time. We have had nothing but amazing supportive collaborations with HealthCand, the FDA, EMA, MHRA in the UK. People want to see these programs move forward. One of the things that we've always aligned with is safety is paramount for us. We do not skimp on anything that has to do with safety. I think that's where we fully align. Our efficacy data may not be 100% because it's never 100% in these rare diseases programs. But safety is always paramount. I think that's why we've always gone along with the regulatory bodies and have a good understanding. There are people in the end. The reviewers are individuals, people that see these children, see the hardships of these families and really want to help. We've been very fortunate. Now, the second part to your question, which is this landscape that we're in now, I think we had a big loss with Dr. Marks leaving the FDA and Dr. Radon in the change-ups. I'm really hoping that the new administration will see the pain that rare disease families go through. The difficulty it is to get a drug to a formal BLA and approval based on the current requirements by the FDA and will allow us to have exceptions to get to the end because the reality is we can't spend a quarter of a billion dollars on a manufacturing P.B.Q. batch or the requirements to get to those items. We need leniency in order for us to get to the end. I think what we're hearing from Dr. Maccary and Dr. Prasad is that these things are going to be allowed and the publications that are being released are saying that as well. We're almost there and we're hoping that when we get there, they will allow us to see these through. And what do you think are some concrete steps that you or regulators could take to support the advancement of these clinical trials? I think fundamentally, and it hasn't happened yet, but I think we need to lower the bar or set a different standard for ultra rare conditions. You know, we're not going to be able to meet them in you factoring requirements. It's just something that is just not possible. 3PPQ runs process validation. It's just the cost for just too exponential to put in perspective. It would take 100 years of drug product to meet those requirements. And we can't leave an open 90 because insurers are not paying for the trials. So we have to find a path to approval. I think the other thing we also need to do is bring back the peer of E, the prior review voucher. It has to come back. It's the fundamental core for rare diseases and how we get funding. And not only just to fund our current programs, but to allow us to do R&D and to help us get more therapies to children. I think it's fundamental that it comes back. Would you say that when it comes to a regulatory pathway for an ultra rare disease, everything but safety should be flexible? Yeah, I mean, everything, everything but safety should be paramount. I think also what we look at, you know, treating children, I mean, we also have to look at the risk versus reward, right? And if we are treating a four to year old that is immobile and they have some slight adverse events, we have to take that into account and understand what those look like. So even with safety, I think there has to be a sliding skill, especially around fatal conditions and what we might be looking at, you know, but safety has to be paramount for sure. Yeah, absolutely. Well, Melpita recently received both rare pediatric disease designation and orphan drug designation from the FDA, which are important milestones. What do these designations mean in practical terms for a therapy like Melpita? Yeah, I mean, initially for for funding, it was while the peer review was around, it helped us get funding from investors in philanthropists right now because it's not around anymore or paused. It's been very difficult. I think what it does help is when you get to the end, it provides you a funding vehicle to pay back your debts and pay forward R&D. And then for the orphan disease designation, it allows you to recoup some tax tax breaks that may have been accrued over the years. But initially, it's really a vehicle for us to get investment or get loans to move things forward. Have you seen these designations influence the project's momentum so far? Or is it still too early to tell? They again, they would have if the peer of he continued, but because it's expiring in September, everybody's waiting on pins and needles to see if it gets renewed. So right now, if you need investment and your program is ultra rare, until that peer of he gets renewed, it's almost impossible to receive funding. Is there anything our listeners could do at home to help? Obviously, besides donating to the cause or could they write letters to their senators to try and make sure that this gets extended? Yeah, I think all I think the rare disease community has to come together as a whole. We can't be this, you know, this spirit parts all over the place anymore. We have to come together on two fundamental items. One is rare disease funding and rare disease, you know, laws and government agreements similar to the peer of he voucher. We have to come together and basically say, this is important. We need it back as soon as possible. And that we are seeing the blowback from the Biotek Arctic winter that we're in right now, that it has to come back and we have to do something to move forward. The second thing we have to come together on is newborn screening. If we're ever going to get to the point of curing these kids early on, we have to treat them at one week, you know, less than a month old. And we're not doing that by all of us advocating for our own diseases to be on the newborn screening panel. We need to come together as a whole and say, we have to get the whole exome sequence or genetic screening on the newborn screening panel. And what's going to, well, that intern, what happened is it allows us to reduce the overall debt on society by reducing the amount of time that these children go into the hospital and all those things. So in the end, everybody benefits more importantly, the children, the families benefit because they may never have the disease or they may have a light version of it. Whereas, you know, today they're going to they have no option but to go through this unfortunate path of finding out your child has a very disease. You know, God willing, there's a treatment you get treated. But if not, then you have to go down the diagnostic odyssey, create a therapy and just like what I did. It's very true. I mean, especially once there is a gene therapy or an ASO available, so many of these diseases that I've heard of are so time dependent, the sooner the better. Yeah, like look at all gensma you don't treat a child before two years of age. They miss out, right? And absolutely. And or crab a disorder, you have to treat the children within one month. These are the kind of things we really have to, you know, tackle. I know that country's like Spain are really ahead of us. For example, if a child goes into the to the doctor's office and they don't know what's going on with the child, the first thing they do is a whole like some sequence. You know, Michael was a night 18 month diagnostic odyssey. Those shouldn't happen anymore. You know, like it should be that you go in the seizures, microcephaly, spasticity. We don't know what it is. Blood draw, a whole like some sequence. But we do have to get a newborn screening to it so we can start saving these children. So on a sort of cheerleading note, I know that some of the SPG 50 superheroes that you've met have obviously influenced getting this to clinical trial. So can you name names? Can you tell us about some of your contributors, scientists, biotech partners and regulators who played a pivotal role in advancing Melpita? Yeah. I mean, the FDA was a pivotal role in our phase one, two in our phase three approval. The Spanish government at Amps was amazing in regards to allowing compassion to use not for just for children from Spain, but in refugees and other children from around the world to be treated in Spain. They've been instrumental. The Italian regulator, IFA, they've been amazing to us and they've been very supportive of the Denmark governments. All these individuals, all these governments have been instrumental. All the employees at Amps, the consultants, all the people connected to us, all the family members that have raised millions of dollars in funds to pay the drug product to fund the clinical research to fund the hospital costs. We're all instrumental for us getting here. It's not on me. It's on me. You know, we're all working on this journey together. And we're never going to get there unless we work together to do it. This is impossible. Otherwise, can you name some of the scientists who have contributed to Melpita? Yeah. I mean, Lauren Black was instrumental from Charles River, Dr. Steven Gray, Dr. Xinshin from UTSW, Dr. Ina Cohen from UTSW, who treat these children, Dr. Bonham and Dr. Barry Burns. You know, the problem is I'm going to forget someone. I'm going to be really upset about myself. So I don't like name dropping. Sure. But you know, there's, there's, it's been a doctor, Dan Balderson, who has been there since day one, the Suad Keith Rachel from my team, Taylin, the all instrumental people in this journey, you know, and again, if I left someone out, if on our purpose, you know, I love you guys and you guys don't support us. But it's been a team effort. That's the way I guys say it's been a team effort and we would not have even got anywhere close to here without having an amazing team. So with Melpita gaining momentum, can we look ahead at what the future holds for this therapy and for the rare disease innovation more broadly? So like what's next for Melpita? Yeah, our hope is that we, we are able to follow to the FDA, get approval for SPG 50, that the pure bees renewed, we're able to take those funds and exponentially grow how many programs we take on. So let's hope that we can get to 10 more programs, get them onto the clinic. Get those 10 programs approved by the FDA and then exponentially grow to 5th year 100 because the reality is my team and I are not here to, to just make a dent in one program. We want to make a dent in the world and we want to treat as many children as we can. So that's the only way to do that is exponentially grow through funding mechanisms, who grants three more children, get more therapies to children and get these approved because if we get them approved, then they'll get to all the children in need. They'll get the newborn screening panel and everything will be just be just free-flowing in a cycle. Do you see this journey as a model for other rare disease communities where families can kind of drive innovation from the ground up? Absolutely. I mean, I hope people don't have to go through all you know. We went through it in the amount of money we have to raise and everything else. I hope it's a lot easier, but it is a model that if you don't give up and you are committed to seeing this through it is a possibility. You can do this. It is not impossible. I'm just a regular guy that did this and so can you. But again, it takes a lot of willpower and you have to just sacrifice everything to get here, but it shouldn't be like this. It shouldn't be that a parent has to raise for an $1.5 million. It has to be, has to learn how to do all these things and project manage this and work while you're doing this. It shouldn't be like that. It should be some mechanism that is better than this to save these children. Well, Elpita has a consulting branch. So what advice would you give to other parents or advocates who are beginning their own rare disease journey. Yeah, I would say that unfortunately you know, you're starting off with a journey, you're not going to have that much money and try to do it on your own and if you need help reach out to me and I'm more than happy to help out. But you know, at a certain point you're going to need a team of people after you consult and CMC consultants, toxicology consultants, you're going to need to know how to write your pre-AID 90 documents and and if you need help we're here to help you and and know that there's other people out there to see this through and help you get to that to the finish line. If you could share a message with the scientific community, the industry or regulators, what would it be? I think just work with urgency, you know, I think that I know that we're all busy and we all have a lot of things going on. But in a lot of these conditions, everyday matters. Like for example, C-Lens 7, B-ZZs, we met a family in December, we told them, you know, you only have about 12 months before your child is too far gone. The family quit their jobs, raised $3 million in like two months. They went all out and now we're trying to, you know, quickly make this drug and every day matters to this to this child and these families. So I would just say please work with urgency because these children just don't have time and everyday that we lose on one side, we lose 10 days on the other. So we just need to just work with urgency. Oh yeah, definitely agree. And what legacy do you hope to build for Michael, for Elpita, or the broader rare disease community? I'm hoping that by publishing our documents and by showing a path forward with different regulatory bodies, that people can easily just copy what we're doing that they don't need to be experts in this. And that, you know, with our partnership with the FDA and the leniency they've given us and the support they've offered us, that people can easily follow our path. That's our goal that our lessons learned and what we've done should make things a lot easier. That is our ultimate legacy that we hope for. Yeah, I'm making all of your data public is very generous, but it's also eminently practical. I mean, there's not going to be any more advancement if people don't start sharing their failures more often. Yeah, I mean, the publishing the protocol, a lot of people to to look and see these documents and be able to go and say, hey, I can have a template that's easily usable right here. Finally, how can our listeners support your mission of helping to bring hope to families affected by SPG 50? Yeah, I would say because now we're helping more families and more foundations, what I would say is, if there is a family near you that's working on trying to make a therapy for their children, reach out to them, offer them help, offer them support, offer them to maybe do an event for them. Because these families are working very, very hard to get there. They put their life on the line. They're, you know, they put themselves in the line and they need support. So I would say if there's a family in your community, please help them. The second thing I would say is, if you have a friend, a family member, a neighbor that has a disabled child, you know, buy them coffee. How have a talk with them because having a disabled child is very difficult. And I think sometimes people just want to be heard. So if you have a neighbor, a friend, an relative, anything like that, just, you know, be like, hey, let's grab a coffee and let's move forward. Well, thank you, Terry, for being on Sounds of Science and for sharing your powerful story and the incredible work of Elpita Therapeutics. Thanks for being here. Thank you so much. You're really appreciated. I'm honored to be on this podcast. Thank you. Terry Pirovelakis is CEO of Elpita Therapeutics. Stay tuned for the next episode of Sounds of Science. Until then, you can subscribe to Sounds of Science on Apple Podcasts, Spotify, Stitcher, or wherever you get your podcasts. Thanks for listening.