BOSTON—We last caught up with Sarepta CEO Doug Ingram in January, right after the JPMorgan Healthcare Conference. In the CEO seat for just a few months, Ingram told FierceBiotech about his plans to move the biotech beyond the "controversial" and "one-hit wonder" labels that have followed it around since the FDA's approval of Exondys 51, its Duchenne muscular dystrophy treatment. At BIO, we chatted with him about Sarepta's pipeline, its latest hires and how the healthcare landscape must change to make way for gene therapies.
FierceBiotech: Earlier this year, you told us about growing Sarepta beyond this "controversial" Exondys 51 company—what's on the horizon for you? What are you excited about over the next year?
Doug Ingram: The problem is I'm excited about everything. Including outside collaborations, we have 21 programs in development. I feel sort of "mission accomplished" on becoming a multiplatform, multipipeline company. And we have the resources to fund our 21 programs.
We started 2018 with $1.1 billion to fund R&D, so we're in good shape there. We have, broadly speaking, two big platforms. First platform is our RNA technology, which started with Exondys 51, which is part of what we call our PMO technology. We have golodirsen there, which we will submit to the FDA by the end of year and hopefully get approval next year.
The great thing about this PMO technology is that it's precise and safe. It gets down to the RNA level and does exon-skipping. It modifies messenger RNA so it can make in-frame dystrophin. But it does have a limitation—the PMOs are neutrally charged, meaning they don't get into cells as efficiently as we would like. So they moderate the decline of disease, but our goal down the road is to do something even more profound. Rescuing decline is the ultimate goal.
We are advancing six PPMO therapies, the peptide-conjugated version of our PMOs, which will cover about 43% of the DMD community. One of them is in the clinic, with five more in preclinical IND-enabling studies. If the PPMO tech works, it will not only be fantastic for kids with DMD, but it also allows us to move beyond DMD and into other therapeutic areas.
FierceBiotech: And what about your gene therapy pipeline?
Doug Ingram: We have eight gene therapy programs in development. Three are in Duchenne muscular dystrophy and five are in Limb-Girdle muscular dystrophy. While the PMO treatments are bespoke and precise, the gene therapies are agnostic to mutations, so we can go in and treat as many as 100% of kids with DMD. We'll be providing an update at an R&D day on June 19 regarding the first two kids in our gene therapy program.
We are building a gene therapy division, the head of which we just announced a couple of days ago: Louise Rodino-Klapac. Without hyperbole, there couldn't be a better scientist to run it. This is first time I've talked directly about the fact that there's going to be a gene therapy division. Louise is going to report up to the chief medical officer. We've just announced our new CMO this morning and I'm equally excited about getting Gilmore O'Neill to Sarepta because he is just absolutely fantastic.
FierceBiotech: We have to ask—it looks like your last CMO, Catherine Stehman-Breen left about six months ago. Can you comment why she did and who has been holding the fort between then and now, with Gilmore coming on board?Doug Ingram: First of all, I have a mission to become a profoundly important genetic medicine company and I need a CMO that fits that role. It was simply a fit issue. Stan Bukofzer came in on a contract basis to keep the trains running while I searched for a CMO, and that gave me the luxury of not letting things fall off the rails.
FierceBiotech: How do you think about pricing as you move forward with your pipeline? What are your considerations? Do you think the healthcare system has to evolve and do you think it will do so—for lack of a better word—willingly rather than reluctantly?
Doug Ingram: I think it's going to be really interesting. Gene therapy, if it works, offers healthcare a complete shift in the way we approach disease. How we think about pricing therapies is going to play an enormous role in whether investment in gene therapy continues successfully.
These are one-time treatments that hopefully have curative effects and that's exactly what all of us in society should want. The interesting thing is, the healthcare system is going to have to evolve and embrace these things. Not just for these therapies, but for the motivation for future therapies. It's not me. It's the investors—I need to go get money from them and they'll give us money so long as we get this right.
I haven't done the math on it yet, but I'll bet you that the cost-benefit analysis is going to be a no-brainer. I don't think that's going to be the problem. The cost-benefit analysis is going to drive a perfectly fine number—a big one—and the healthcare system is not going to know what to do with that number. Because our healthcare system has historically been built around chronic disease. And so what do you do with one-time events that are really curative? So I do think we're going to have to evolve the healthcare system to deal with these curative events and I think it's less evolution and more revolution.
FierceBiotech: Do you think the healthcare system will evolve proactively, as companies like Sarepta are working on new therapies, or do you think it will be more reactive?
Doug Ingram: If I can be a bit immodest, I think it is companies like Sarepta that are going to play the largest role in figuring this out because we, the genetic medicine-specific companies, are the most focused in this area. Companies like Sarepta ought to be thinking hardest about these issues because we're not diluted in our thinking.
There are two ways to do this. One way is just develop our therapy, we just go: "Here's the cost-benefit, pay X and you figure out how to get it done." That's asking a lot of them. It might be better for us to try to help figure it out now and come up with a new structure along with it and that's one of the things we want to think hard about.
FierceBiotech: How do you think about designing trials and measuring outcomes, especially for novel approaches in orphan diseases that may not be as well or easily understood by investors or the general public? How do you communicate what an outcome actually means for these kids, versus something more familiar like survival rates in cancer?
Doug Ingram: It's a constant and nuanced issue. One of the best ways to get to right place on what's meaningful is to engage with patients, their caregivers and their healthcare providers. That's what we have to do to get to a better understanding. Objectively getting that figured out and properly communicating that to regulatory agencies and the like is important. And of course, this all has to be in the backdrop of creating validated functional endpoints that are meaningful to regulators. First and foremost, it has to be driven by evidence. And your evidence base is from patients, caregivers and physicians as opposed to us sitting in a room imagining what is important to somebody.
We're trying to do more and more of that. For one of our recent trials, we held a patient advocacy advisory board to talk about trial design, endpoints and the like. It's very easy to forget that and miss that step, but we are continuing to focus more and more on that issue. It's not just respectful to the community, but also really enlightening for us.