All right. Good morning, everyone, and welcome to day two of the 41st Annual JP Morgan Healthcare Conference. My name is Dave Praharaj, and I'm an Associate with the JPM Healthcare Group. Today I have the pleasure of introducing REGENXBIO, along with their President and CEO, Ken Mills, who will be giving the presentation. After the presentation, there will be some time for Q&A. Thank you and take it away Ken.
Thank you Dave, t hanks to the JP Morgan organizers. I especially want to acknowledge John Whittaker on the banking team, who's always a strong advocate for REGENXBIO at this conference and in general. Let's see, a ction. Making reference here to the fact that I probably will make some forward-looking statements during the presentation today and additional information about any statements I may make or information to back them up can be found in our SEC regulatory filings. I'm gonna start the presentation out today with just a quick story. I have a colleague t hat colleague has a parent who has a disease called wet age-related macular degeneration. It's a disease that's the most common form of blindness. Many of you may be familiar with it, i t's late in life onset, and when left untreated, it can result in complete vision loss.
Since the mid-2000s, innovations in the understanding of biology as well as development of medicines have resulted in a series of treatments that are highly used and have become the standard of care. They're referred to as anti-VEGF agents, t hey involve repeat injection into the eyeball, typically maybe every month or every other month. When patients receive these, they eliminate the progression of the disease. It's really some of the most amazing outcomes I think that have been observed in the treatment of different forms of blindness. When I hear and think about these treatments and standard of care about this disease, I suddenly see new and different types of burdens that have been created with the introduction of these important medicines.
My colleague who tells this story about this family member, he himself is actually a retina surgeon and was involved in the clinical trials that supported the development of these anti-VEGF therapies and will tell you about this burden, will tell you about the requirements that go into making sure that his family member gets to clinic and gets these injections. Because if they do not, they absolutely continue to progress with the disease. This particular person, who, of course, is familiar with the biology, familiar with the practice of medicine in retina and is incredibly diligent and has access to the ability to get their parent for these regular injections, is absolutely rigorous about it. Think about all the people that are not, t hink about the people that can't access monthly or every other month clinical injections.
Think about those types of people in the United States or Europe and Japan. Think about those types of people outside of those jurisdictions. Then imagine what it would be like if that treatment was converted into a one-time treatment. Not every month, not every other month, not putting the type of burden for compliance and the lack of convenience, but the necessity, but giving that same result of maintaining vision and stopping the progression of the disease. So for systems and people that cannot accommodate taking a day or two out of every other month or so to get those types of injections, for systems that can't support the inventory and the infrastructure to deliver those types of medicines, and frankly, for the lack of convenience and its troubling lack of compliance even in the United States.
REGENXBIO has a mission that's about seeking to improve lives through the curative potential of gene therapy, part of that mission is to focus on treating that disease that I just talked about. We were founded in 2009, o ur headquarters are in Montgomery County, Maryland. We're just outside of D.C. we have approximately 400 full-time employees. We're a company that's building more than just a single treatment for the most common form of blindness. We have a leading pipeline of one-time gene therapies for diseases that affect the brain, the muscle, as well as the eye. We have advancing research and development capabilities to extend gene therapy further and deeper into current diseases and expand the focus of our pipeline.
We also have a strategic partnership with AbbVie to develop and commercialize the gene therapy that I was referring to for the most common form of blindness and other adjacent diseases. In the middle of 2022, we opened a brand new Manufacturing Innovation Center that's been producing clinical-grade vector for us since the middle of the year, and we believe will support commercialization of our gene therapy treatments. At the end of the 3rd quarter, we reported $614 million of cash on hand. Really our biggest event for 2022 was the introduction of our new strategy that we call 5x'25, which is to introduce five late-stage or commercially available gene therapies as a company or in partnership to the market by 2025.
Today I'm gonna focus on a few of the programs that are a key part of our 5x'25 strategy. Here's a complete look of our pipeline. All of our investigational gene therapies use something called an adeno-associated viral vector. It's AAVs that are part of a proprietary gene delivery platform that we have that we accessed years ago. We call it our NAV Technology, for those of you that aren't familiar, AAV vectors are non-replicating viruses, delivery vehicles, basically viruses that are not thought to cause disease in humans. Our platform consists of exclusive rights to a large portfolio of AAV vectors that were identified and isolated really in one lab at the University of Pennsylvania. We believe this platform is a very strong foundation for all of our current research, certainly our current clinical stage programs, and our ongoing research and development.
We refer to our clinical and commercial investigational stage AAV vector and gene therapies as AAV Therapeutics. Coming into 2023, our team is laser-focused on executing on two pivotal phase programs. I think that makes us unique as a pure play gene therapy company in AAV. One of those is a pivotal program that's going to probably enroll close to 1,000 patients for wet age-related macular degeneration across two trials, t he other trial is in a rare disease. Both of these are trials that are ongoing in 2023 with an intent for our first BLAs to be filed in 2024. Otherwise, the team has plenty of work t here's probably about 10 clinical trials ongoing within the company. In November of 2021, we closed a commercial partnership with AbbVie.
The focus was on bringing AbbVie's excellence in development and commercialization of treatments in eye care together with our AAV program for wet age-related macular degeneration and other diseases that benefit from one-time gene therapy using the anti-VEGF biology appropriate pathway. At the time that we announced that partnership, we received $370 million in upfront payment from AbbVie. We're eligible for close to $1.4 billion in development and commercial milestones, and we also elected out of the gate to partner on the potential commercialization of treatments in the U.S. with a 50/50 profit share. Outside of the U.S., REGENXBIO will receive royalties. This was really an ex-U.S. play for us as a company w e were looking for a strong partner.
Our infrastructure and our capabilities were largely focused in the United States and Canada, and we were looking for a partner to be able to take us into other geographies. We will and have continued to lead execution on the late-stage clinical trials, certainly on the clinical manufacturing, and we will support, be the primary source of support we expect for the commercialization and the manufacturing support at the commercial scale. This is a quick snapshot of the five or so clinical trials that are the subject of the partnership between REGENXBIO and AbbVie. You can see there's actually a long-term follow-up that's continuing from a first-in-human study that we did with our investigational candidate that started in, like, 2017. Since 2020, we're here referencing ATMOSPHERE and ASCENT.
These are the two pivotal clinical trials that we're running in wet age-related macular degeneration. All of these trials use something that we call our subretinal delivery of our investigational agent for anti-VEGF treatment. We've also introduced within the last couple of years, a new delivery mechanism for the same pharmacological agent. Both of these deliveries are directly into the eye, one-time treatments. They deliver the pharmacological agent into different compartments of the eye. We've been using a tried-and-true method with respect to the subretinal approach. It's actually a delivery method that's the subject of one of the few approved AAV gene therapy products today. We've been looking to continue to advance the opportunity to expand access and expand ease of delivery with something like the suprachoroidal delivery approach.
The subject, and I'll get to it, of the partnership is a product candidate that we call RGX-314. It's one time, as I keep emphasizing, i t's an AAV vector that encodes essentially an anti-VEGF antibody, similar to standard of care. Of course, we've, you know, turned the pharmacology on its ear here. The PK is that it's there constantly, it doesn't require any sort of re-injection. The AAV therapeutic itself transduces cells within the retina, that expressed anti-VEGF antibody is secreted from those cells and acts locally in the back of the eye where diseases like wet age-related macular degeneration are occurring. In advance of our partnership, we had established that RGX-314 was well-tolerated and efficacious at several doses when delivered directly into the eye by both of the routes of administration that I've been referring to.
Our subretinal delivery has the largest data set to date and the longest set of data that we've been able to generate. We have patients that have been enrolled and on treatment from one-time dosing of RGX-314 out over five years, and we've reported on data and durability up to four years. At clinically meaningful doses, we consistently show changes in retinal pathology that evidence benefit with respect to wet age-related macular degeneration, improvements or stabilization in visual acuity. Most importantly, when we enroll patients in our clinical trials with RGX-314, we're actually taking known disease patients who are already receiving standard of care treatments, and we're looking to transition them to a non-reliant protocol, basically eliminating their rejections, injections.
And you can...m aybe you can see, but I can see, and I can report to you that in the lower quadrant of this slide, we are seeing, certainly a spectrum, but in some cases, people who we would consider complete responders, those who have gone four years without ever receiving an injection of standard of care anti-VEGF treatment again. Also a series of partial responders, maybe people that have gone from monthly injections or every other month injections to maybe one or two year. In the first-in-human phase, we also some people that were non-responders as we were sort of exploring this for the first time.
Overall, if you sort of averaged out the outcomes for the 42 or so patients that were part of our first-in-human intervention study, we saw somewhere between 70%-80% reduction in anti-VEGF burden with stabilization or improvement in visual acuity, with stabilization of retinal pathology. I emphasize the visual acuity part 'cause as we transition into the pivotal phases of development, here we're going to be focusing on visual acuity as a primary endpoint for those ongoing studies. Here's a graphical representation of the two ongoing studies as I referenced. These are, you know, large phase III studies with active control arms, differentiated from our first-in-human exploration. We're still enrolling the same types of patients, basically diagnosed and diseased wet AMD patients who are receiving therapy and enter our protocol.
We follow them in the two different dose arms and look at basically those measures that I referred to, including visual acuity at monthly visits. We have an active control arm, which is the comparator, where we're either looking at every month delivery of a drug called Lucentis or every other month delivery of a drug called Eylea in the two separate studies, ATMOSPHERE and ASCENT. You can see that the relative size of those studies are differentiated. That's substantially because both of these studies' endpoints are based on non-inferiority with respect to changes in visual acuity between the experimental arms and the control arms, and the statistical powering that's required between the two different drugs with respect to the control arm. Clinical research continues with AbbVie on the suprachoroidal delivery approach.
Our suprachoroidal program is ongoing with enrollment in basically two phase II studies, one for wet age-related macular degeneration and another for a disease called diabetic retinopathy, which is also a sort of known and labeled indication for anti-VEGF therapy. We're focused here on single-action, one-time treatments to address substantially similar pathologies in these types of diseases or to potentially prevent progression of these diseases at all when patients are diagnosed. I'm gonna show you evidence from one of the phase II trials we have where we've actually enrolled approximately 90 patients in the wet AMD trial for the suprachoroidal delivery. What you're gonna see basically here is that, again, early on in the study, we're focused again on stabilization or non-inferiority.
We actually have a comparator arm in this phase II study. We're looking for sort of similar outcomes with respect to changes in measured visual acuity, multiple dose levels. Here's a little bit easier slide to read, where we've been looking at the sort of natural history requirements of injections in these patients and then transitioning them into our protocol and looking at the reduction in injection burden on an annualized basis. You can see here again, somewhere between 70%-80% reduction on a mean basis is achievable with a one-time gene therapy, even though we still have a population of complete responders, and we have a population of what I would refer to as partial responders.
With respect to suprachoroidal, this is still, frankly, the suprachoroidal delivery device is being pioneered by REGENXBIO with respect to AAV therapy. We're the first ones to deliver AAV with suprachoroidal. Therefore, our investigation was also significantly weighted towards safety evaluation. With respect to that point, we've done a sort of rigorous examination of different common ocular adverse events in this study. At some of the most recent doses, we've acknowledged some of the more common events include ocular inflammation, conjunctival hemorrhage, and some modest increases in intraocular pressure. All of these are trace or mild characterizations, but also the AbbVie and REGENXBIO teams have elected to introduce new dose protocols with prophylactic steroid, in particular, to see if we can completely eliminate or reduce the incidence of this mild intraocular inflammation.
We expect that those are cohorts in this trial that are ongoing and may report data out once we complete enrollment, perhaps as early as later this year. That's a little bit of a look into RGX-314 and what's going on in a pivotal phase and what might be behind that with respect to new delivery mechanism. Gonna move on to a pivotal phase program that we have for a disease called Hunter syndrome. It's also called mucopolysaccharidosis type II or MPS II. MPS II is part of a class of diseases that's a single mutation, a single genetic mutation disease, within the lysosomal storage disorder class.
Hunter syndrome is got some adjacent cousins in the MPS families, and it has existing standard of care in the form of enzyme replacement therapy that's delivered intravenously, marketed by Takeda Shire, a drug called Elaprase, to address the peripheral symptoms of this somatic disease. However, there is no treatment currently in Hunter syndrome for the neurological manifestations of this disease, and the intravenous delivery of the enzyme replacement therapies do not cross the blood-brain barrier, and they don't have an effect on the neurological complications and effectively the neurodegeneration and what ends up causing death in these young boys.
We have something that we call RGX-121 for MPS II, i t's designed with an AAV vector to deliver the human gene that is missing in these boys with respect to putting it directly into the cerebrospinal fluid and letting being taken up in as many of the CNS cells as possible. We think that in addition to transducing cells and changing the intracellular machinery by putting this enzyme back, we also get. There's evidence of secretion, expression, secretion, and uptake of that enzyme by other cells. There's this kind of neighboring effect that also allows us to, once we achieve gene therapy transduction, affect benefit in adjacent cells as well. We're very excited about kind of the benefit of a gene therapy in this particular disease because of that phenomena, because of the significant unmet need.
We have other programs that aren't as far along, but have also started either...e ither completed first in-human intervention, for instance, in MPS I, which is about the closest cousin to MPS II, severe version called Hurler syndrome, as well as the CLN2 form of Batten disease. We consider this a platform. It all uses the same vector, it all uses the same manufacturing process, it all uses the same clinical intervention. The difference is the interchangeable part is the gene that's defective in each one of the different diseases. For MPS II in the CSF, we have shown near normalization of the substrate that is the active substrate of the enzyme that's missing in these kids, and that's deficient in or missing in Hunter syndrome.
We've shown it in such a way that we have evidence in the natural history that that substrate change, specifically in the CSF, has a meaningful correlation to neurological outcomes in these kids. We recognize that we're getting the intracellular changes, and we recognize that those intracellular changes are important for the clinical outcomes of these boys. We view that we have a surrogate biomarker here in order to support an approach with regulatory agencies for the unmet need in Hunter syndrome, which is significant on the basis of a surrogate biomarker. The ongoing phase III study has started in the second half of last year and will continue through the early part of this year. Again, their second pivotal stage program that's executing this year will be finishing out the clinical trial.
We'll be finishing off the sort of process qualification to support commercial scale, and all of this will feed into a planned BLA filing in 2024. The last program that I'm gonna talk about is outside of pivotal phase. It's just a little bit of a view into our research pipeline, and it's based on a rare disease called Duchenne muscular dystrophy, which many of you may be familiar with. Duchenne is a rare disease caused by mutations in a gene called dystrophin. It's a protein of import when it comes to cellular stability, structure, and function, particularly in skeletal muscle and cardiac muscle.
Without dystrophin, the muscles lose their ability to sort of function properly and eventually trend towards apoptotic cycles and of course, you know, effectively clinical muscle wasting that affects breathing, and that affects heart function, and it affects mobility. There's presently no cure for Duchenne, but there are a series of treatments that are maybe not satisfactory when it comes to disease modification. Gene therapy approaches have emerged, and there are some in late stages of development. Our treatment is of a similar class to AAV Therapeutics that I would refer to as a truncated dystrophin, functional dystrophin, or micro-dystrophin products.
That's because we can't quite fit the full gene of dystrophin into an AAV therapeutic, so we've taken out some of the domains, and we tried to retain some of the functional domains with respect to dystrophin to maintain clinical functional outcomes and importance. In our particular case, our chief science officer and scientists at REGENXBIO designed a micro-dystrophin that is actually different than some of the others that are in clinical development, because they've included a C-terminus domain element of dystrophin into our micro-dystrophin concept. What we've shown and what's been reported, even independent of AAV therapeutics, is that the addition of this C-terminus can improve the recruitment of key proteins and the sort of stabilization of key function with respect to muscle cells in general.
We've also done some other things to optimize for manufacturability and for safety. We have an IND that's been approved for this investigational candidate that will start dosing patients this year. This is a genetic disease that largely found in boys, two doses, up to 18 patients. Plan for enrollment in the U.S., Canada, and maybe Europe should be initiated in the first half of this year. Just a couple points of wrapping up now. We've been around for a long time, or at least I feel like we have been in the gene therapy space, 2009. We became a public company in 2015.
We've been operating, expanding our capabilities and infrastructure since that time to achieve this point where we have late-stage clinical development programs and a strategy like 5x'25 . There's a part of our history that's also been a lot about partnership and enablement of new treatments in general as a company, either through license, company formation, or even acquisition. This is just a list of the companies that have access to REGENXBIO now technology under license. One of them, Novartis, has one of the first commercially approved AAV gene therapy products for a treatment of spinal muscular atrophy. That SMA treatment, Zolgensma, I think on an annualized basis, helping at least a kid or a family a day, had achieved close to $1.3 billion in annual sales. We receive royalties from that product.
At the end of 2020, we actually monetized a portion of that royalty stream and brought about $200 million in gross proceeds onto our balance sheet to continue to invest in our own capabilities and pipeline. I talked in the beginning, and I'll just revisit again, manufacturing. Our Manufacturing Innovation Center in Maryland is state-of-the-art. It's critical for our success in execution on the 5x'25 strategy. It's now a part of sort of a seamless end-to-end engine that we have inside of the company to take basic research, target discovery, candidate optimization, process development, early GMP manufacture, all the way through to 2,000 L scale, which is to our knowledge, to my knowledge, the most significant scale that exists across the entire industry in all of AAV.
We do so with a level of quality and a level of rigorous analytical support that I think is unparalleled when it comes to AAV manufacture. It's really been driven by people who are not AAV experts, but by people who have been recruited to the company with years and years of biologics and vaccines development and commercial manufacturing and supply chain experience. One of which we just announced yesterday, I promoted to Chief Operating Officer, Curran Simpson. Would certainly welcome anyone to. If you're in the Rockville, Maryland area and wanna come by and see our Manufacturing Innovation Center, it's actually got glass windows, so you can see inside, see the bioreactors, see the entire train. We've also recently installed a final fill and finish capability that will come online in 2023.
We've been making GMP material in this facility since the middle of the year. As I mentioned, with respect to our AbbVie partnership and collaboration, we are the commercial and clinical supplier of late-stage development and the commercial launch of RGX-314 in that partnership. Finally, some numbers and a little bit of guidance. As I mentioned, I think maybe I said 614 , I think, my CFO will be angry. I left $3 million out of our balance sheet at the 2022 Q3 earnings report. We feel like we're in a good capital position to be able to execute on the late-stage development programs that we have, the build-out, and now, you know, we're sort of on the tail end of the capital investment in the Manufacturing Innovation Center.
The expansion of the pipeline, the execution of over 10 clinical studies, as I mentioned, I mean, there's probably now, if you include REGENXBIO partners, certainly Zolgensma, three or 4,000 patients and families that have benefited from REGENXBIO NAV technology in some form of clinical trial, commercial access, expanded access, I think in many cases with important and meaningful outcomes across a whole array of different types of diseases and therapeutic targets and tissue types. It's an execution year, but we expect that several of our clinical trials will also have the opportunity for updates in the second half 2023 with interim clinical updates. I just wanna say again, I, you know, sort of started with the story about the colleague and the friend.
I have another friend and colleague who was actually one of the co-founders of REGENXBIO, the scientist clinician. His lab was the discovery center for the NAV technology. His father calls on him from time to time and asks, "Hey, what's happening with that RGX-314 program? All of my friends really need that treatment." That was supposed to be a funny little anecdote on the part of Jim Wilson. I just want to acknowledge again, thanks for JP Morgan for inviting us. Thanks for listening to me. I think, did I leave enough time Dave, for Q&A?
Yeah. We roughly have 10 minutes for Q&A.
Please hold your applause until after.
If anyone has any questions, please raise your hand and ask it, and we can bring a mic around. All right, I guess. You know, I'll kick it off. You know, there's gonna be a lot of activity this upcoming year. What are like your top three milestones that you're most excited about?
Yeah, I'm just pulling up my pipeline slide here again, if you don't mind, to address that, 'cause that's where the activity is. You know, I mean, I think, you know, the goals are commercial products by 2025, and BLAs are sort of the transition point for that. It's completing the enrollment of the pivotal trials in this year for RGX-314 as well as RGX-121. Our Duchenne program, I think, is something that we've been really eager with sort of the new scientific element to show some of the first human clinical data on.
Being able to enroll patients in the first half of the year in that first human study, puts us in a position to be able to report interim clinical data with respect to safety, biomarker evidence of the gene therapy turning on and functional evidence of the gene therapy starting to have an effect on the Duchenne boys, potentially in the second half of 2023.
In terms of the cash balance that you mentioned, How are you gonna go about allocating that in terms of focus?
One of the things about sort of the use of cash this year is with respect to the AbbVie partnership. When we launched the partnership, we sort of went through this transition period in terms of cost share, and we were still bearing some of the costs just because it was sort of natural order of doing so of things that were already ongoing. We're now over a full year into the partnership and, according to sort of the contractual agreement, and I think what made sense with respect to the AbbVie and REGENXBIO teams overall, it now transitions to the majority of costs to AbbVie. There will be significant increased cost in the RGX-314 program over the course of 2023.
The actual distribution of that from REGENXBIO's perspective is likely to at least be flat or maybe even go down as AbbVie is probably paying close to 70% of the full cost of development now for RGX-314 t hat's one thing that has an impact. We've given guidance that we'll be able to take the cash that we have on hand into 2025. You know, the next areas of focus for us are getting the BLA for Hunter syndrome filed with the FDA, making sure that the investment in the manufacturing facility continues to support those BLA filings. I mean, the clinical execution is one thing, but going through the qualification of batches to support BLA filings that are upcoming are also incredibly important on the team with respect to execution this year.
We're really hopeful that we'll get the sort of origination of first-in-human dosing going for Duchenne, so that by the second half of this year, RGX-202 can be in sort of modes of expansion of patients based on safety, either at the first dose level or dose escalation.
All right. I guess, is there anything else that you'd like to mention that wasn't discussed?
Everything that I wanna mention, I have mentioned or is available in our SEC filings. Grateful for the time today.
Anyone else with questions? All right. Well, I thank you for listening today and have a great rest of the day.
Thanks.