From One to Many

When Terry Pirovolakis’ son Michael was diagnosed with the ultra-rare neurodegenerative disease spastic paraplegia type 50, he set out to raise money and engage researchers in developing a treatment. Now, after successfully dosing Michael with an experimental gene therapy as the first patient in a clinical trial, he has launched Elpida Therapeutics to develop multiple gene therapy programs for children with ultra-rare diseases. We spoke to Pirovolakis about the need Elpida is seeking to address, its unusual business model, and why he hopes to hand off its therapies at no cost to a partner once they win approval.

Daniel Levine: Terry, thanks for joining us.

Terry Pirovolakis: Thank you very much for having me.

Daniel Levine: We’re going to talk about your own journey as a parent with a child with an ultra-rare neurodegenerative disorder, how you work to get an experimental gene therapy created for your son, Michael, and how through that process you now have launched Elpida, a company seeking to develop gene therapies for ultra-rare disease populations. Before we talk about Elpida, I thought it would be useful to remind listeners about your own journey and how it led to the creation of the company. What is spastic paraplegia 50 and when was your son Michael diagnosed with the condition?

Terry Pirovolakis: Yeah, so spastic paraplegia type 50 is a slowly progressing neurodevelopmental neurodegenerative disease that causes paralysis from the toes working its way up to the shoulders, and typically children with the disease are paralyzed from the waist down by the age of 10, quadriplegic by the age of 20. Some have epilepsy, some don’t, some have microcephaly, some don’t. But the majority of children are nonverbal and usually do not walk by the age of 10. My son was diagnosed on April 2nd, 2019, and on that day, me and my wife made a promise that we would do everything humanly possible to give my son a better life. And that journey led us to flying around the world and meeting experts in gene therapy in the disease that Michael had. And we were fortunate enough to find Dr. Steven Gray, Dr. Xin Chen from the University of Texas Southwestern Medical Center, who agreed to do whatever it took to help us as well. Imported a mouse from England, dosed a colony of mice, proved it in cells with the NIH, and basically did a complete proof of concept showing that it was relatively safe and effective in mice with the disease. From there, we manufactured the toxicology batch with a company called Viralgen in Spain. We applied to the to the FDA and Health Canada through a CTA and a pre-IND, and we did toxicology through Charles River for non-human primates and rats that showed that it was relatively safe. We then made a clinical batch and I received approval December 30th, two years ago and dosed my son on March 24th of last year.

Daniel Levine: When he was first diagnosed with the condition, what treatment options existed, if any, and what were you told about the diagnosis?

Terry Pirovolakis: Yeah, we were told—the doctors were really nice to us and they told us, “Listen, there’s not much known. There’s very little known about the disease. Go home, love your child, give them the best life humanly you can, but there’s no drug and there’s no treatment at this point in time.” That’s basically what they told us.

Daniel Levine: You set out on an effort to get a gene therapy developed to treat Michael. I should note you are not someone who began this effort with a deep background in biotechnology, but worked as a director of information technology in the financial services industry. How did you go about doing this and what gave you the confidence you’d be able to be successful?

Terry Pirovolakis: Honestly, throughout my life and my career, I’ve done very challenging and difficult work building things that people didn’t think were possible, and I think that was time. I was trained for this task to try to save my son by doing all these very complex things that again, people thought were not possible. And on top of that, we had a lot of luck and a lot of prayers along the way because a lot of this journey is around safety and animals that may or may not work out, and manufacturing runs that run perfectly and a whole bunch of other things that just have to be—the sun and the moon have to align basically for you to get it right. And we just happened to get it right, especially considering that instead of doing everything we did in series, we did everything in parallel. So in other words, instead of spending five or six years and four and a half million dollars, we did it in three years or just under three years and four and a half million dollars. So we were very fortunate that this thing just happened to work out.

Daniel Levine: I encourage a listener who wants to learn more about your experience to go into our archives and listen to a Rarecast we did with you in October 2022. Fast forward though, you’re now launching Elpida Therapeutics in the hopes of bringing gene therapies to many patients in need. Elpida is a social purpose corporation. The goal here is to make gene therapies, not money, but it has an unusual business model. Can you walk us through how Elpida works?

Terry Pirovolakis: Yeah, and just to step back a bit, I mean, after we dosed Michael, we had two more doses and we decided that we were not done. So, we basically set up a clinical trial at University of Texas Southwestern Medical Center for a phase 1/2, and we dosed one patient two months ago, and we have another patient being dosed in a few weeks. And then I went to Viralgen in Spain and I said, there’s a few children in Spain. If I end up bringing the trial here and I paid for the cost, would you manufacture a batch to support these children? And they said, absolutely. So, I flew out there in December and we met with a team in Pamplona at a hospital and we’re working on dosing six more children across Europe, part of that study. And then what was happening is I was doing a gene therapy 101 class and every month 50 patient population groups would join. So, we’ve trained almost 200 so far, and it was this huge unmet need, and I was thinking to myself, how am I able to make the biggest impact? And it wasn’t running the gene therapy 101 class and it wasn’t helping these families on an individual basis, which I do anyways. It was getting these drugs to approval because if we dose two or three kids and that’s the end of it, we did a disservice to this entire population. What we need to do is we need to get the drug from proof of concept to approval, get it into the insurers, get into the government’s hands so they can pay for it. Because at $800,000 to manufacture the drug and $400,000 to $500,000 to administer the drug, only the rich or people that can raise money really well will get the treatment. And our goal is to get the treatment to everyone no matter what your religious, social, economic status is, every child deserves to have a better life than the one coming to them from these terrible diseases.

Daniel Levine: During your efforts to develop a gene therapy for Michael and others with SPG50, you were fortunate to build a lot of relationships and win the goodwill of many people and organizations that helped advance the work. How are you leveraging that for Elpida?

Terry Pirovolakis: Yeah, and that’s how Elpida really started. After coming up with this idea, we first thought of a philanthropic mechanism to try to start it, and it was just not possible to raise the money we needed. And then we thought about a VC model, and unfortunately we just had to give up too much money, which would be limiting in the next step. So, I went to all the partners that we made partnerships with over time, and I said, “Hey, if I were to take on five programs and run them to the clinic, would you support me? Would you give me in-kind services to run these programs?” And one after another, they said yes, and I was kind of taken back, but I knew that their heart was in the right place, and that’s where Elpida came to be. So, the goal is to take five programs to the clinic. Our goal is to get two or three of them to approval, and by leveraging the PRV voucher that comes with approval from the FDA, do between 12 and 16 more programs with those funds. So, exponentially grow the number of programs that we’re doing, getting them to the clinic, getting them to patients and seeing it through. So, our goal is roughly around 10 patients per program, 50 kids initially, and then if we get 12 to 60 more programs, another 10 per program, so 12, 120 to 160 children on the next phase.

Daniel Levine: To date, you’ve been able to raise about $20 million in commitments from partners for in-kind services. Can you give a sense of the range of things you’ve been able to cobble together and the services they’re providing? How far will that take you?

Terry Pirovolakis: Yeah, so right now we have about four or five different manufacturing runs, two or three toxicology programs, about 50 kids to be dosed across different hospitals. Some of them are in-kind, some of them are deferred payments, and then one of them, we had to get a loan for paying our employees in the seed funding, but all of that is either one-to-one or in-kind, very low interest or no interest at all in order for us to get the ball moving.

Daniel Levine: You’ve been able to raise some seed capital on top of that, but you’re still looking to raise funds for operating expenses. How much do you need to raise here and how far will your funding goals take you?

Terry Pirovolakis: Yeah, I think we need to raise $3 to $5 million for five years. That will get us to the end of all five programs, seeing them through, and I think at that point in time, then if we get one or two PRVs or even one PRV, we will be set. We’ll be self-sustaining, and that was kind of the purpose of it, which was having these companies help kick us off, get us going so that we could be self-sustaining and move programs forward on our own. And that’s kind of what we’re trying to accomplish.

Daniel Levine: It’s mind blowing to think of a company with five gene therapy programs being able to advance those on so little capital. How is that possible?

Terry Pirovolakis: I think what it is, we have a lot of partners that are willing to give us in-kind services as well as not just dosing patients, also intellectual property lawyers and expertise when we need it. But I think the reality is that we’ve built a really good team around what we’ve done and we’re going to use those same lean methods on doing all the other programs as well. We’re not a large company. We don’t have 50 or a hundred employees. We can run very lean and remember, we’re taking programs after proof of concepts. We’re not spending all the time doing R&D. It’s mostly process development, right? It’s like taking them to the IND, the pre-IND, the IND, then doing the toxicology and manufacturing, getting the treatment, all that kind of stuff. So, we’re not really doing a lot of research and science. It’s mostly process development.

Daniel Levine: You’re focused on ultra-rare disease populations. Ultra-rare is a term that’s quickly outliving its usefulness. What size populations are you targeting?

Terry Pirovolakis: Usually it’s under three to 500 worldwide. That’s kind of what we’re looking at. We haven’t really defined it by patient population. It’s more of is there a really good proof of concept, is there really good data to support this program and is there commercial interest? And if there’s no commercial interest, but there’s a lot of good efficacy and a lot of good data, then that’s a program that we’re very interested in because these are the programs that are never going to see the light of day unless we help them.

Daniel Levine: Elpida doesn’t plan on marketing gene therapies, but to hand them off to a commercial biotech or other partner at no cost once it wins regulatory approval, these aren’t expected to be products that are economically attractive to a biopharma or others. What’s the expectation? Why would a partner take on one of these products?

Terry Pirovolakis: I think if we’re in the market that we’re in right now, when these all come out, I think it’s going to be very difficult. I think if the market is a bit different and it’s a bit more upbeat towards gene therapy, I think it’ll go a lot further. What we’re hoping is that regardless of what the market looks like, that a company like Roche or Novartis or Pfizer or some big company will do it for philanthropic purposes, realizing that, hey, these are three to five programs or more, because there can be probably other companies that will be doing something similar like BGTC {Bespoke Gene Therapy Consortium] and other entities, and we have to have a mechanism to get these drugs to these patients. These children deserve it, and I’m hoping that by then we can convince again some large corporation to take this on through a philanthropic means.

Daniel Levine: It’s a pretty radical business model, and it’s based on a couple of key assumptions. I’d like to ask you about those. The first is that you’ll be able to get FDA approval for a gene therapy on a small single trial. What gives you that confidence?

Terry Pirovolakis: Unfortunately, there isn’t that much confidence in it. I think the reality is that regardless of what we name it, I think if we do a number of children, like a small enough population of the actual bigger disease and we’re able to show efficacy, I think that’s where we’re looking for. Because if we’re able to show efficacy in, let’s say dosing every single U.S. patient for a specific disease, then we’ve done all we can. And as long as we show efficacy in that disease or surrogate or a biomarker, then we should be able to get approval from the government, from the FDA.

Daniel Levine: The gene therapy for SPG50 did get a rare pediatric disease designation. That’s a critical part of the economics of what you’re doing. The plan here, as you said, is to get a gene therapy approved and sell the priority review voucher that the FDA grants the therapies with a rare pediatric disease designation. Those have been worth about a hundred million dollars. The assumption here is that you’ll be able to consistently get rare pediatric disease designations and that the FDA will continue this program, which seems a bit uncertain at least a few years ago. Walk me through your thinking there.

Terry Pirovolakis: Yeah, I mean, the reality is if the rare pediatric disease designation or the PRV vouchers go away, then rare disease as a whole is doomed because that’s a significant amount of money that a lot of foundations, a lot of companies are looking and requiring in order for them to run the programs. And if they don’t get that, if that funding goes away, we’re going to see a significantly more amount of programs being dropped. So, I think that the reality is that if there’s an inkling of it going away, all the rare pediatric or rare foundations around the world really need to step up and start really advocating because if it goes away, literally we we’re going to see a lot of programs shelved and we’ll probably never see the light at the end, unfortunately.

Daniel Levine: Elpida is virtual today. It’s not staffed with a discovery and development team. Where will the programs in your pipeline come from and will there be a cost to acquire or license them? Will academic centers turn over IP without economic consideration?

Terry Pirovolakis: They haven’t yet, and we’re not expecting them to. The reality is that universities are not going to hand over IP. Patents will still be owned by them. What we’re hoping to do is that they come back with reasonable amounts or reasonable terms, which a lot of them, to be honest with you, a lot of them have come back with very reasonable terms considering the low patient populations because, again, we want to make them appealing when we hand them off. I don’t think that’s really going to be a problem, to be honest with you and how we’re going to find programs. Today we found three programs that we’re very interested in taking on, but the two additional ones, we’re going to allow patient populations to apply, similar to BGTC, and then our scientific advisory board is going to help us select the best programs that have the most efficacy, the most safety, and some natural history data.

Daniel Levine: Given that all the stars have to align for this to work, is there a plan B? Are you thinking of ways to change the business model so it could be sustainable if any of the assumptions change?

Terry Pirovolakis: I think people usually are fixed in their ideas, and what we’re doing is we’re basically saying we’re adaptable and we’re flexible. And I think that’s been kind of the point from the very beginning is that we’re moving this forward, we’re being adaptable based on market conditions, and we’re taking on programs that people thought we could never do or do something that we thought they would never happen. And as things come up, we’re just going to have to adapt and change. And I think the reality is that based on what we have today, when we’re able to dose 50 kids and get five programs into a late phase trials, I think that’s a huge win overall for the entire industry. But our goal is to get these approved, and that’s something that I’ve committed to and that’s something that I plan to achieve.

Daniel Levine: Terry Pirovolakis, CEO of Elpida Therapeutics. Terry, thanks so much. As always.

This transcript has been edited for clarity and readability.