Founder Stories: Bobby Gaspar, Manufacturing Hematopoietic Stem Cells

Welcome back to The Business of Biotech, Cell and Gene edition. I'm your host, Matt Piller, and I'm joined by my miniseries co-host and cellandgene.com chief editor, Aron Harris. Aron, great to see you.

You too, Matt.

So today's show is a cool one for you, Aron, because our guest, Dr. Bobby Gaspar, is an esteemed member of the Cell and Gene editorial advisory board. For his part, Dr. Gaspar is a renowned scientist, physician, and business leader. In fact, a gene therapy pioneer who founded Orchard Therapeutics in 2015, served as chief scientific officer, and just this spring was appointed CEO. Dr. Gaspar has additionally spent the past 28 years as professor of pediatrics and immunology at King's College London. Dr. Gaspar, welcome to the show.

Matt, sorry, it's UCL. I'm a professor of paediatrics and immunology at UCL rather than King's. That's probably a— I wouldn't normally correct, but that's probably an important point to get right.

Well, that is an important point to get right, and I appreciate you doing that. I don't know where I got that misinformation. It's 2020. It's the year of misinformation, so I'm glad you corrected me on that one. So now right off the bat, I want to apologize for the makeshift studio that we're in and the potential sacrifice to our audio. I'm up in Northwest Pennsylvania where a winter storm is dumping enough snow on us that I'm not really inclined to take the hour-long drive up to our studio in Erie, so here we are. With that apology aside, Erin, where would you like to start with Dr. Gaspar?

Thanks, Matt. Dr. Gaspar, thanks so much for being here. This is great. As Matt explained in his intro, you founded Orchard in 2015. But your team really has its roots in research and clinical development involving ex vivo autologous gene therapy. So talk to us a little bit about why your research led you to launch Orchard.

Well, Erin, Matt, thank you very much. It's very kind of you to invite me and give me the opportunity to talk. I really appreciate it. Thank you. So I think in your introduction, Matt, you talk about my past life, as it were, which is I'm an academic clinician by training. So I started off training as a pediatrician. And maybe I'll just talk you through kind of the journey that I've been on, which is how Orchard kind of came into being. As I say, I started off as a pediatrician, and quite early on, I went to a specialist hospital in London where you look after very severe genetic diseases. And I was looking after very severe immune deficiencies, so children who, as a result of a genetic defect, are born without immune systems. And, you know, there are only very few centers that look after kids like this, and at Great Ormond Street Hospital It's one of the specialist centers. And these were really devastating conditions. The children would— without any treatment, children would die in the first year of life because of very severe infections. And the only way to treat them was a bone marrow transplant, which involves taking blood stem cells from a donor individual and giving it to these individuals. And this is going back into the early '90s. And the complications associated with the bone marrow transplant meant that you know, many of the children would die from the complications of the treatment. So it was a very poor outcome that they had. And, you know, I was fascinated by the science behind this condition, but also by the limitations of current therapies that were available. And it was in a very nascent era of gene therapy. And the thought was really, why use somebody else's bone marrow stem cells, which can have all kinds of complications, why not use the child's own bone marrow stem cells? And then, because there was a gene that was missing, why not put a working copy of the gene into their bone marrow stem cells and give it back to them so that they now had a correct copy of the gene and the correct information to build a new immune system? And, you know, quite frankly, I just thought this was, you know, fascinating, uh, you know, both from a scientific perspective and the possibility of what this could do from a clinical perspective for patients. And so in fact, I was involved in one of the first gene therapy trials, I mean, certainly in the UK and worldwide, in treating a child with this form of immune deficiency. It was called severe combined immunodeficiency, or SCID. And this was back in 1993, very, very early clinical trial. It didn't work, but it kind of gave us some understanding of the process and the limitations, etc. And so together with a very close colleague and friend who I've worked with for over 25 years, I went into the laboratory to learn about this science, this new science that was emerging, which was essentially trying to introduce genes into hematopoietic stem cells, so they can now integrate the gene into those cells, modify the cells, and give those cells the correct information to build a new immune system. And so we developed work in the laboratory and then actually used that work from the laboratory, translated into clinical trials. So we treated our first patient in 2001, and that boy still comes back to clinic today with a functional immune system after once-off administration. Of gene-modified cells. And when you see how that works, and when you see the benefits that that can provide, I mean, it's the most rewarding thing I've ever done or will ever do, I suspect. I mean, it was extraordinary. So we then did that for one disease, we developed it for another disease, etc. We went through some of the trials and tribulations of developing a new therapy. But what we were able to see was a really profound impact upon patients and a durable impact upon patients as well. And see, then in the kind of early 2010 onwards, we started some— a new wave of trials. We developed the technologies. We entered a new wave of trials. And one study that we did, I treated the first patient in 2012. As we were treating these children on these clinical trials, it was partnered with a trial in the US as well in California. Basically all the children survived and all the children, or virtually all children, were recovering their immune systems as a result of this therapy. And my colleague in UCLA was getting referrals from all around the US and from Canada. I was getting referrals from all over Europe. We had a child from Australia come to access therapy, and as I say, the results were really very, very encouraging. And at that stage, we— I think we realized that this had to now be made available to patients on a global basis. We couldn't just sustain children coming to one or two centers to access therapy. This now needed to be made into an approved genetic medicine that could be used by patients globally. And in order to do that, really the only way to do that was to take it into a commercial entity that would then build the infrastructure, the regulatory expertise, the manufacturing expertise to make it into a medicine that could be used by individuals globally. And that's when the concept of creating an entity that could do this came about, not just the one disease but a whole series of diseases using the same approach, the use of gene-modified blood stem cells. And so that was the, you know, the genesis, the idea behind creating Orchard. And at the same time, there were— there was a lot of interest from the venture world into gene therapy, and we had investors who were very keen to follow this path. An investment company called F Prime talked to us for a long period of time, and then decided to invest and start Orchard. That's how Orchard came into being in September 2015. It was really— and to a certain extent, my journey has really been one— it's been a single path, really, which is really to try and deliver better outcomes for these severe genetic diseases using this HSC gene therapy. And I did it in the academic setting. I've been very determined to make sure that this is followed through to be able to be made available to larger numbers of patients as an approved medicine, hence the Foundation Orchard, and hence me kind of stepping into the role of initially Chief Scientific Officer and then CEO.

Yeah. Had you had any prior experience with the formation or governance of a startup biotech, even from a funding standpoint, or was this just totally brand new territory for you?

I mean, Matt, if you'd said to me at any stage in the past that this was going to lead to a company or any kind of commercial enterprise, I would have said you were joking. I mean, really, I had no intention that that would be the case. All we wanted to do was really offer the best treatment for patients with the best science. And it was really only when we started to see the effectiveness of the therapy and the effect it was having on patients and the fact that so many physicians were asking us for access to the therapy and referring patients, we thought, well, this would need to go to a commercial entity. So I've been a clinician and scientist throughout my career, so it was a complete new stepping stone for me. I think what I want really was to make sure that this gets out there as approved medicines for patients.

Yeah, yeah. So I'm interested in your role in those formative years as Chief Scientific Officer and founder. I guess it's a two-part question. I'm interested, one, in your role as CSO in sort of the formation of the organization, the governance, that kind of thing. And two, if you had a do-over, if you could go back to those kind of early formative years from the context of being the chief scientific officer and get a do-over, you know, do something differently, what might that be?

Yeah, so when I stepped, I mean, so actually when the company was founded, I was a CSO really on a part-time basis while continuing my academic and my kind of laboratory and clinical commitments. But then as Orchard just grew, then it was clear that there needed to be a stronger scientific basis within the company. And that's when I stepped over more full-time. So it was an incredible learning experience for me, because obviously, when you come from academia, you work in a certain structure. And then you come into the biotech, and one that was starting really from scratch, and you're building the company right from the beginning. So it was a hugely exciting time. So I learned a hell of a lot about how a company is put together, the governance that is put in place, the people that you need to bring on board. And although I was not directly responsible for that, I could see how it was evolving and was involved, obviously, with the appointments and things like that. So things have evolved, and I stepped into the CEO role in March this year. And we did make some changes even when I stepped into the role. And that's part of, as you said, if you kind of track back and think about what you could have done differently, that was part of the reason for making those changes. So I think one thing, we were on 3 sites. We were in California, Boston, and London as well for quite an early stage biotechnology. And I think That's quite complicated from an organizational perspective. The time zones can make things difficult, especially for such an intense young company. One of the changes I did make was to slim down our operations in California and we moved all our technical operations to one site in London. Although we have some very important key people in California, The majority of the company is based in London and Boston to kind of give some, I say, some greater emphasis on the organizational structure. I think the other thing as well is that the excitement around this HSC gene therapy approach, and I say, you know, what we had clinical data already coming into when we started Orchard But we also licensed in programs from elsewhere using the same approach. And we suddenly had a company that was taking forward quite a large number of programs, all at late stage with significant clinical data, as well as early-stage programs as well. And although that was a great opportunity and a kind of an abundance of riches, it's also difficult to manage all of those programs all at the same time with the kind of the manpower and the resources that we had. So again, one of the things that I did when I first came in was to give some greater emphasis so that we weren't doing everything together, but looking at where we place our emphasis now and how we can sequence the program. So that was another change. And I think, you know, again, you know, looking back, we should have been kind of phasing this more, you know, or sequencing the advancement of the programs rather than having to take everything together at the same time.

Yeah. Good position to be in, though, given the fact that— I mean, I hear time and time again from emerging biotech leaders that many shots on goal is a good thing, just perhaps a better organizational structure of those shots.

Correct. Exactly. Exactly. Because you want every shot to kind of hit its mark, especially when you have such great data. You want to make sure that everyone kind of fulfills its potential, gets approved, et cetera. And try to do everything at the same time takes a huge amount of bandwidth and resources. And it's kind of sequencing that, I think, is one of the learnings.

Sure. And as you've honed the organization from certainly 2015, but as you said, this has been going on since the '90s into the 2000s. And you, as Orchard, and your team have had extreme success with HSC gene therapy and having others access it, but there have to be a slew of challenges associated with it, right? So can you talk us through the challenges associated with treating rare inherited diseases?

Yeah, I think, you know, so I think that I'll kind of start that by saying almost that I think that this whole— right from the beginning, you're stepping into new territory. Right from the beginning, throughout the 25, 28 years that I've been doing this, you're always breaking new ground. And it's no different now because it's getting to the next stage of that path. So when we were doing the first clinical trials, when we were first talking to the ethics bodies or the regulators, we're almost working with them because they've not approved these kind of therapies before, or they hadn't, you know, given the manufacturing was at that stage, you know, was when it's in its kind of embryonic stage, etc. So I think every step of the way you are creating new ground and you're working with the regulators, authorities, agencies, etc., to ensure that this moves forward in the best, in the best way. So I suppose some examples of that are, are manufacturing. So we're making cell and gene therapy products for commercial use that have never been made before for that purpose. And so that is something that, you know, we work very closely with the authorities to ensure that there is robustness of manufacture, that it meets all the appropriate accreditations and qualifications, etc. So, you know, and that sometimes is a bit of a learning process. The way we manufactured vector and cells in our first trials were for academic purposes, not for commercial purposes. And so we had to move that from academic to commercial for one of our trials. In other programs, it started off in a commercial entity, which has made it much smoother to go all the way through. So I think manufacturing is certainly something that requires a lot of attention in order to make sure that it is appropriate for a commercial use. I think the other aspects that we are, you know, we will be kind of going through is we've just had through the EMA our first CHMP positive opinion for a very severe neurodegenerative condition called MLD. And by the end of the year, hopefully we'll have the positive approval from the EU. But that allows us to commercialize next year and launch this product. But that also requires us to engage with reimbursement agencies for reimbursement of a once-off therapy. And again, that is something that really hasn't been done before. So reimbursement agencies are used to paying for therapies that are given, you know, daily or weekly or monthly and not just once. And that's a different model of reimbursement that we have to look to. And again, it's another, you know, change in the kind of the current paradigm. It's, you know, pioneering a new way of reimbursement. So that I think is, you know, another area that will, as I say, is a challenge, but it also, it's something where we'll be breaking new ground. I think the other part of it that I think is very important is in these rare diseases, which are often very severe, you need to get there early in order to get the best outcome for patients. And so again, as an example, MLD, where children are born normally but after the first year or so they start to lose cognitive ability, the ability to move and maintain independent motion, then you have to intervene early before the disease has had time to take hold in order to get the best effect. And we've seen that in our clinical trials, the children that were treated either pre-symptomatically or in the very early stage of disease, the ones that have the best outcomes. So then diagnosis, early diagnosis becomes absolutely key to making sure that children have the best access and the best outcomes for therapy. So again, one important element there is how do you now make the community aware of the disease? And it's an ultra-rare condition. How do you make them aware of that? How can you implement things like newborn screening for this, where newborn screening was never thought about before for MLD because you couldn't do anything about it. And now here's potentially curative therapy available. So the impetus to screen these babies at birth and provide the therapy as early as possible becomes ever more important. And so that's something that we have really kind of tried to facilitate within the community, engaging stakeholders funding pilot studies to look to see whether an assay is available that can detect these patients early. So, you know, these are the kind of challenges that we will face, not just for MLD but for other programs as well. And I think that's how we're responding to those challenges, you know, working with the community for newborn screening, working with the reimbursement agencies about, you know, the potential of a curative therapy and how that can be reimbursed and looking at payment models, etc., working with our CDMOs for manufacturing to ensure that that is as smooth as possible as we go into the commercial arena.

The Business of Biotech is brought to you in partnership with SciTiva. Together, we're committed to helping the leaders of new and emerging biopharma companies navigate the financial, organizational, human resources, and regulatory waters you'll encounter on your way from discovery to the clinic and beyond. Check out a host of useful resources for biotech leaders at Cyteva's Emerging Biotech Accelerator at cytevalifesciences.com/emergingbiotech. That's cytevalifesciences.com/emergingbiotech. I'd like to just real quick unpack a couple of those a little bit more. And I want to start with the latter, right, the one that you just mentioned around getting to patients early and the work you're doing around newborn screening. I mean, it's admirable that you would take the initiative to create that assay, you know, figure out how newborn screening might take place. What sort of, I guess, hoops and ladders— hoops must you jump through and ladders must you climb to pull together, right, the clinical, like the clinical level at hospitals to be able to You know, there's a protocol, right? When a baby's born, there is a protocol. Now here you are saying like, let's insert another objective into this protocol. Give us some more color on how you manipulate all those moving parts to try to make that happen.

Yeah, great question. And I hope my answer won't be too long in trying to answer that. So actually, you know, I have, I've been kind of quite involved in newborn screening because Again, in my academic and clinical life, I— the conditions I was dealing with, severe combined immunodeficiency, again, devastating disease, but if you can get these patients early, you can get a much, much better outcome. So I had a very strong view that these babies should be screened at birth, and the test actually became available through scientists developing that, and I championed it in the UK and the EU and kind of advocated that it should be implemented into national screening programs. And I learned then how much this involves, because this isn't a scientific or clinical issue, it's a public health issue. And there's so many different stakeholders that have to be kind of engaged and bought into making this happen, because it's, it's not just about the test, it's about the natural history of the disease, the impact that early diagnosis can have in providing the evidence for that? Is there a therapy that is available that can make a meaningful difference? And then the other important thing is, you know, does the test— how robust is the test in terms of picking up disease cases but not giving false positives? Because you're going to screen, you know, the entire population of newborns. And if you have a lot of false positives, that can create problems as well. So there are all of these considerations. And then the final bit of that is the health economics of screening and does it make a difference. So there are all of these different aspects that need to be considered, and so many, many different experts need to be brought in to create a case for newborn screening. So I had a lot of experience in that for SCID, so I've used that experience to help for MLD. And so There is an assay that is now available. We didn't develop the assay, but we worked with the scientists that were developing the assay, and then we've brought together the stakeholders, multiple stakeholders, to initiate and fund pilot studies. And one will start in Germany very soon, one will start in Italy, there's going to be one starting in New York State, and hopefully the data from those pilot studies will start to give us confidence that this can pick up patients with MLD robustly. It doesn't have a high false positive rate. And so by doing that, we can then help initiate pilots elsewhere, but also use the data for implementation of national screening programs, both in the EU and also in the US as well. So it doesn't happen easily. It doesn't happen really rapidly, but I hope we can do it more with the learnings from the past. We can do it more quickly than previously and really be able to ensure that patients get diagnosed and be able to access, you know, what is a potentially life-saving therapy.

Yep. Okay. And then one other follow-up on that question around the challenges. You mentioned, you know, taking your therapy from academia to commercial and working with a CDMO in that mix. We're looking for a quick response to this one. If you could give one bite-sized piece of advice to a company in a similar scenario, you know, taking something that's you know, not— doesn't have a whole lot of precedent from academia to commercial-scale manufacturing with a CDMO. What would that bite-sized piece of advice be?

The bite-sized piece of advice would be try and start with what you want to use at the end. Yeah, so, you know, even if you can go to a CDMO that can manufacture at commercial, you know, the process that you start with, try and keep it the same the whole way through. Because once you make a change, it, you know, just kind of the comparability exercise that you have to go through can be, you know, quite significant. It's doable, it's, you know, but, you know, it does involve cost, it involves transfer of technology and processes, etc. So the fewer changes you can make along that path, the smoother the path will be.

Yeah.

Sure, Dr. Gaspar, so at Cell and Gene, we talk a lot about how cell therapy, gene therapy is, could be the future of modern medicine, right? And so, as you were explaining with MLD, all of it, HSCs particularly, you know, and earlier on you were talking about how to help avoid the bone marrow transplants. Is this an example of the future of modern medicine as it applies to cancer treatments?

Yeah, well, let me— I'll come to the cancer bit in just a second. I do think that— I think there are— I talk about something like gene therapy as being almost like a toolbox. And it's a— rather than being one thing, it's a series of different tools. And HSC gene therapy is one tool in that toolbox. AAV gene therapy would be another tool. Specific gene editing would be something else. And I think what you need to do is to look at what is the disease that you're, you're trying to correct, uh, what is the gene, what is the cell that you need to correct, and which is the best tool to be able to, uh, to have that effect. So I think HSC gene therapy can be applied to a whole series of different conditions, but not every condition, and there are different tools for those other conditions. Having said that, the HSC gene therapy approach, because HSCs, the hematopoietic stem cells, become multiple different cell types, so they can become immune cells, they can become red blood cells, they can become cells that actually traffic into the CNS, into the brain. They also traffic into other tissues as well, the gut, the liver, et cetera. So by modifying HSCs, you have the ability to correct multiple different cell types, multiple different tissues. Therefore, that's why even with an orchard, we're correcting immune deficiencies, we've been correcting neurometabolic disorders, we've been correcting hemoglobinopathies as well. Then now we're looking at maybe correcting larger forms of neurodegeneration, all using the correction of hematopoietic stem cells. I think that's where that potential lies. When you start talking about cancer, I don't know that necessarily modifying HSCs is the way to correct or treat cancer, but certainly correcting the immune system and, you know, through engineering T cells which to be able to fight cancer cells, I think will have a significant role to play in cancer treatments. And it's already obviously having an effect in leukemias with the approval of Kymriah, Yescarta, and sure there are others, there are others to come. But, you know, you can also— now people are looking at, well, can you engineer T cells to fight solid tumors as well, which hasn't yet, but, you know, I know— I think there is an awful lot of work trying to do that as well. So correcting the immune system and harnessing the immune system to be able to fight both liquid tumors and solid tumors, I think, will play an important part in cancer therapy.

Sure, and you're talking a lot too about the unmet medical needs, right? And so talk to us a little bit about that. How do you see gene therapy really affecting unmet medical needs, even things we're not even sure of yet? Yeah, where do you see it going?

Yeah, so this is, you know, um, something that we've been thinking about quite a lot at Orchard. What we saw really, and again, it comes down to the biology and understanding the mechanism, what we saw in a condition like MLD, a severe, you know, rare neurodegenerative condition. What we're seeing is that you correct hematopoietic stem cells, and a subpopulation of those cells have the ability, a natural ability, to cross the blood-brain barrier and engraft in the brain. And they engraft as these cells called microglia, and they start to secrete the gene that you've introduced into these cells. And these cells, this gene can be taken up by neurons and prevent neurodegeneration. And we've seen, you know, long-term correction of the disease in patients with MLD. Now, this gives you a route to deliver therapeutic genes in the CNS. And so we've been taking that approach and applying it to other rare monogenic neurometabolic conditions. But we're also now thinking, well, why can't we use that for larger conditions, larger forms of neurodegeneration? And so we recently talked about a program that we're starting preclinically in a genetic subset of frontotemporal dementia. So frontotemporal dementia after Alzheimer's is the second most common form of dementia. There are certain genetic susceptibilities that have been identified. There's one gene called progranulin which affects approximately 5% to 10% of patients with frontotemporal dementia. And so now we're looking at whether we can use HSC gene therapy to address this much larger form of dementia. So I think this is— we also talked about ALS, amyotrophic lateral sclerosis, which again, very common neurodegenerative condition. And again, can we modulate specific pathways through modifying hematopoietic stem cells and getting those cells to deliver that modulating gene and protein in the CNS. So this now opens up a kind of a whole possibility of being able to address more common conditions where it's not just a single gene that is affected, or you're trying to affect a pathway rather than a single gene, or in the case of FTD, there is a genetic susceptibility. We also have been thinking about, well, given that these HSCs can migrate into other tissues, well, what other organ-specific diseases can we address through this approach? And similarly, from our learnings in an immune deficiency which has a very severe form of colitis, which we have seen can be corrected through HSC gene therapy, we're taking that understanding to think about larger forms of colitis that could be addressed through HSC gene therapy. And again, it's through the migration of hematopoietic stem cells into the GI tract, into the wall of the gut, and therefore providing a missing gene or missing protein in the gut and protecting from colitis. And so again, we've identified a subset of Crohn's which arises from a specific gene defect in a gene called NOD2 and looking to see whether we can correct NOD2 form of Crohn's using this HSC gene therapy. So what we've learned in the ultra-rare conditions and these rare disorders through the use of HSC gene therapy, we're trying to apply to larger indications.

So we're running a little bit tight on time here. So I want to start to wrap things up a little bit. But I want to give you an opportunity, Dr. Gaspar, to share with us where you're at with the pipeline and what the next big steps for Orchard are. Sort of what's the near-term next big step for the company?

So there are, I mean, I think there's a number of things that, you know, kind of various different stages. So firstly, we have, we're looking forward to the approval of Libmaldi, as it will be known, our gene therapy for MLD, by the end of 2020 and then launching in 2021. We've just opened an IND with the FDA, and so we're looking forward to engagement with the FDA to see how the path to a BLA for MLD as well. So we're in an active engagement with the FDA on that. So I think those are the two very important steps for MLD. In another program, Whisker Lorge Syndrome, we're engaged with the with the FDA and the EMA and looking to talk with them about the timeline to file for that condition as well. So that's again a very late-stage program, very exciting. We have a program in MPS1, another neurometabolic disorder where we have proof of concept data and we want to go to a pivotal study. And so next year is really talking to the regulators about the design of that pivotal study and then opening that pivotal study, which will be multicentric with sites in the US and in the EU. And then there's another clinical study in MPS3A, which is at the proof of concept stage, where we've enrolled 3 patients. We hope to be enrolling the full 5 patients in 2021 and then presenting data on those patients then as well. And again, thinking about how we move forward to a to a registrational study. So, you know, there's a— and at the same time, we are looking at, you know, expanding our preclinical work in these larger indications. So in frontotemporal dementia, in MOD2 Crohn's, we hope to be getting into in vivo murine studies to show proof of concept in those animal models. So it's a, you know, I think about it almost as You know, we have this, and we, as we said at the beginning, almost kind of an abundance of riches. But what we need to do is really kind of execute and deliver on these rare diseases, which is what we set out to do, and build the experience in getting approvals, commercialization, manufacturing, etc. And at the same time, uh, develop HSC gene therapy for larger indications as well. So you kind of grow the value of the company through the rare disease space into larger indications.

Yeah, you know, I'm always fascinated by the different personas of biotech founder, right? Like, you know, you've got your serial entrepreneurs, guys who come from the VC, you know, background, people who come from the academic background. I look at your career to date, and you mentioned it early on in our conversation, it's been sort of a single track, right? Coming out of academia, one company, learning the ropes of governance and organization, moving it forward successfully. I'm curious, and of course, you know, I fully don't expect you to give me the straight answer on this, but what does the rest of Dr. Bobby Gaspard's career look like? I mean, are you, you know, are you planning on sticking with Orchard for the long haul, or is the entrepreneurial bug bitten you to the point where you might be might be interested in gambling on some other biotech venture.

Interesting question. I'll be very— I mean, at the moment, all I want to do—

I put you on the spot with that.

No, no, you have. But all I want to do is to make this successful as a therapy, HSC gene therapy successful for multiple different diseases. I want to be able to get these approved as medicines being used by patients as the standard of care for a whole series of diseases. So that, you know, when, you know, a physician diagnoses a child with SCID or MLD, they say, oh, we're going to treat that child with gene therapy because that's the best way to treat that child. And, you know, here's Orchard that makes gene therapy for, for condition A, condition B, etc. And to do that for all— because I do think it is the right way, the safest, most effective way to treat a whole series of these conditions. And that's what I want Orchard to be able to do. And I think that it will change medicine. I think that for these diseases, they will be fundamentally changed by having these therapies available.

Perfect. Now, give one last question, a concluding thought here. Speak directly to the persona that you represent, that leader of a biotech that has come out of, you know, MD, PhD, come out of academia, and is launching a first-time biopharma. Again, bite-sized piece of advice. What's that direct piece of advice you would give that person as it relates to launching the business?

I think— I mean, I can only talk from my personal experience, but I think you have to look at the patient. You have to put the patient front and center of everything. What is this disease? What do patients suffer from? What is the best way to treat that? Because if you do that, if you follow that, it will have value. And I mean value in every sense. It's value for the patient, it's value for the family, it's value for the ecosystem, the healthcare physicians, everyone around it. And it will be value for the company as well if you get that right. And that has to be at the center. And to a certain extent, I say that because I feel that's what we set out doing. We didn't set out to create a company, we set out to do the best thing for for patients. And it's had value all the way along the line. And I think you can build a very successful business by doing it.

Excellent. I think that's a great place to conclude. I feel like we could talk all day, Dr. Gaspar, but I don't know what time it is there in London. I'm not sharp enough to do the equation in my head. What time is it now?

We're just coming up to quarter to 2 in the afternoon.

OK, well, you need to get back to work and wrap your day up. So thank you. Thank you so much for joining us. It's been a real pleasure. I'd love to have you back on the show because I feel like we've got a lot more we'd like to discuss with you.

Well, thank you very much. It's been very kind of you to ask me on. It's been a pleasure to talk to you both. And I hope I've been able to give you some kind of insight into this area. But thank you very much. I appreciate it.

Thank you. So that's Aaron Harris and Dr. Bobby Gaspar. I'm Matt Piller, and this is The Business of Biotech. We're produced by Bioprocess Online in partnership with Cyteva, which offers a host of great resources for emerging biopharma companies at cytevalifesciences.com/emergingbiotech. That's cytevalifesciences.com/emergingbiotech. Www.sellinggene.com/emergingbiotech. I'd like to thank you for listening. I'd like to encourage you to subscribe to this podcast anywhere you listen to them and subscribe to our newsletter at sellinggene.com and bioprocessonline.com. In the meantime, thanks for listening.