REGENXBIO Inc. (RGNX) Earnings Call Transcript & Summary

Hello.

Hi.

Okay, sorry. I think the music was a little bit longer than we thought. I'm sorry about -- everyone, we are a few minutes late. My name is Gena Wang. I'm mid-cap biotech analyst at the Barclays. I first hope everyone stay healthy and would like to thank all the participants, investors, companies and especially our event team and corporate access team who made this virtual healthcare conference possible. With that, I would like to introduce our next speaker, Ken Mills, President and CEO from REGENXBIO. Ken, I will hand over to you.

Great. Thanks, Gena. And thanks, everyone, who's able to join and listen in today. I'll echo Gena's comments about keeping everyone well and safe. And also thanks to Gena herself and her team and the rest of the organizers at Barclays for hosting us. So everyone should be able to see, hopefully, the cover slide, and we'll be moving on to the second slide, which is our disclaimer about forward-looking statements and just mention that generally more information can be found about REGENXBIO and our programs, of course, in our SEC filings on the web. Moving on to Slide 3. REGENXBIO's mission is to improve lives through the curative potential of gene therapy based on our proprietary NAV Technology Platform. Here we believe single-administration gene therapy treatments can significantly alter the course of the disease in many patient population. We're advancing and broadening our pipeline to access 2 different treatment modalities. I think we have AAV-mediated antibody delivery and monogenic gene replacement. Both of these modalities use our NAV Technology Platform to develop potential treatments for both rare genetic diseases as well as potentially expanding treatment options for diseases broadly affecting public health. In addition to our internal developments, we also have a number of partnerships that we like to highlight, including 1 FDA-approved product and 15 clinical-stage products that are in development, being developed by third-party licensees. That's over 20 programs in total in development. Our team and management at REGENXBIO are experienced drug developers and have been leaders in gene therapy for over a decade since the company has existed. And recently, I'll touch on at the very end, we've been making significant strides to expand our capabilities in and around manufacturing, an area that we view as important for advancing our internal pipeline and programs. And we keep making great strides at advancing and broadening our internal gene therapy pipeline and advancing our key programs. And some of those programs, I'm going to talk about if we move on to Slide 4. So here's an image of REGENXBIO's internal pipeline. We're focused on the development of AAV gene therapies, as you can see, across the 4 therapeutic areas, that is retinal diseases, neurodegenerative diseases, metabolic diseases and neuromuscular disease. Starting at the top, we've recently announced some updated data around our lead program, RGX-314, for wet AMD, and this included a 6-month data from our Cohort 5 of our Phase I/IIa trial. Overall, we view that the data continues to demonstrate not only meaningful reductions in anti-VEGF treatment burden, but also improvements in visual acuity following a onetime administration of RGX-314. And we really remain incredibly encouraged about the program's clinical results and look forward to reporting more data across all of the cohorts throughout 2020. In fact, we expect to initiate a pivotal program for the subretinal delivery of RGX-314 in the second half of this year, and we're working through finalization of the design of a trial based on 12-month assessment of our Cohort 5. We intend to submit the design of the trial to the FDA in mid-2020, that is this year, and begin dosing patients in the second half of the year. Meanwhile, we also continue to have plans to initiate clinical studies using another route of administration approach, which is the suprachoroidal microinjector, the SCS Microinjector, for an in-office delivery of RGX-314. This is delivering RGX-314 to the suprachoroidal space. This is a route of administration that could potentially allow for treatment of expanded populations of patients with wet AMD, diabetic retinopathy in all settings of patient care including in the office. We expect to initiate Phase II trial in wet AMD using the SCS Microinjector in the first half of this year. That trial will build on data from our ongoing Phase IIa study with the subretinal approach of RGX-314. And it's expected to evaluate new dose cohorts using the SCS Microinjector against the control arm. We are looking to have interim data from that part of the clinical development of RGX-314 by the end of this year. And finally, we'll also expect to submit an IND in the first half of this year for the use of the SCS Microinjector in a new population of patients for diabetic retinopathy. We plan to initiate that Phase II trial in the second half of this year. So that's the summary of activities going on around RGX-314, our lead program. Beyond RGX-314, also excited to provide some recent updates, including interim data from the first 3 patients in our MPS II trial, a Phase I/II trial for RGX-121. These are patients with MPS II, despite having availability of enzyme replacement therapy, have significant neurocognitive difficulties which aren't addressed through the use of traditional peripheral enzyme. The initial data from the first cohort that we showed continued to support that RGX-121 was well tolerated. But also, and importantly, we observed consistent and sustained reduction in a key biomarker, heparan sulfate, as well as signs of neurocognitive stability. We've completed and plan to work to complete the dose escalation of the second cohort in this trial and expect to have that completed in the first half of the year, and we look forward to reporting additional data in this program in the second half of the year. Finally, moving on to the metabolic disease part of the pipeline. We have completed dosing for an expanded Cohort 2 in the Phase I/II trial of RGX-501, which is for the treatment of homozygous familial hypercholesterolemia. We plan to assess LDL cholesterol levels after all patients have completed their steroid prophylaxis treatment, which is coming up. And this interim data should be available to us in the first half of this year. Across the rest of the pipeline, the team continues to do a lot of interesting and important preclinical work, including work on the potential treatment for hereditary angioedema, which is based on use of AAVs to express antibodies that are directed at plasma kallikrein, which is a key protein in the plasma contact pathway, left unregulated in patients with HAE. Also, our R&D team, led by Olivier Danos, has been working on the utility of NAV Technology and specifically our AAV8 vector for introducing it to the muscle like some of our other partners have done, including Audentes, now Astellas, that has a treatment for x-linked myotubular myopathy that some of you may be familiar with. As a result of a lot of our internal work as well as observations of external application of AAV8 for neuromuscular indications, we've advanced to a stage where we've evaluated several clinical -- preclinical candidates as potential for neuromuscular disease, and we believe we have the opportunity and the potential to advance at least one of those later this year that we'll identify further. And we feel that we've kind of got the right combination now of understanding the biology, the application of AAV in neuromuscular and, importantly, a real understanding of an in-house expertise, knowledge and capabilities in AAV production and manufacturing to get to scale that's necessary for moving into this particular type of area. And so look forward to providing everyone with more updates on this work in the second half of the year. But the neuromuscular aspect of our pipeline is something that we just recently announced. So I'll wrap up just by, again, finishing with some capabilities. We do have an ongoing construction project for a GMP facility here in Rockville that continues as planned. We announced this last year and the site's expected to provide us with this internal capability to strategically scale production while ensuring and maintaining a high level of quality for patients both in clinical development, also in commercialization. Expect to be capable of, therefore, having a spectrum of early-stage and late-stage programs that are supported by our internal and external supply chain, including things that may require large-scale vector supply. And this facility that we're building in Rockville is on track to be operational in 2021. So overall, in 2020, we're really building on a lot of strong history and progress been made at the company and looking to broaden and deepen our internal pipeline and expertise and advance our key programs over the course of this year. So I thank everyone for that quick introduction. And Gena, I think, I'm ready to move on to some questions.

Thank you, Ken. I would just start with 314 program. You had quite some experience in the past also with intravitreal injection in the eye in addition to a subretinal experience. So just wondering, based on your experience, what could lead to inflammation? And we saw -- in some cases in other programs, we saw early waves of inflammation and then some late wave of inflammation, any thoughts there?

Yes, Gena. I think that when approaching a disease like wet AMD where we know the goal for gene therapy is to move into a well-known, well-characterized, large population of patients, probably one of the largest, I think, that's being targeted for any of the gene therapies in the clinic. And also, I mean, a relatively healthy population of patients. Certainly, safety, quality of materials, scalability become some of the most important aspects of advancing a program like this. And I think when we viewed the benefits of different approaches to treat wet AMD, we started fundamentally with making sure that there was a route of administration and a pharmacology that could kind of support that scale and that breadth and depth from a safety perspective. And then we layered in, certainly wanting to achieve clinical outcomes that were going to be meaningful, at least maintaining the vision, if not improving vision, and durability, of course, becomes so important. Your question related to the safety side of the equation, we've dosed over 40 patients in our current trial with the subretinal route of administration. And we characterize that deeply preclinically from a safety and efficacy perspective, and we're seeing a correlation between what we saw a very safe profile in the animal work that we did with the dose escalation and the expansion that we've been able to do in the human study. The approach that we took was to prioritize that, and it landed us from a sort of programmatic implementation perspective with a procedure that we think is -- has a great safety profile and is showing some really clinically meaningful data in early development and is also an operating room procedure. And I think that when we evaluate that opportunity, if there's something that we'd like to improve about that program overall, it certainly would be able to expand it into other clinical environments. I think when you look to do that with other routes of administration, you have to understand what the trade-offs are there. And I think it's certainly, in our experience, been a challenge to move off of the subretinal route of administration and get the same type of safety and reproducibility in terms of gene expression and, therefore, clinically meaningful effect. Obviously, the environment for wet AMD with the re-injectable biologics is familiar with things like intravitreal injections, but these are proteins that are manufactured, obviously, outside of the body, put into sterile environment injectors and they don't involve AAV at all, of course, in any of, sort of, the things you need to consider in terms of the immunology of AAV when you're introducing it for a transduction. In our experience, subretinal administration, we did not see any inflammation or other safety signals that concerned us about advancing things forward. We didn't implement any immune suppression protocols. We didn't implement really any other meaningful upfront filters on the use of the procedure itself. The procedure does involve, again, the use of an operating room and a vitrectomy and all the standard things that come along with that. But the results that we've seen in the trial continue to emphasize that we think we're going in a great direction in terms of safety and clinically meaningful end points. When we went to look for alternative routes of administration and how we came upon something like the suprachoroidal system was to continue to have a high bar for safety, continue to challenge ourselves to see if we could find another route of administration that could approximate the type of clinically meaningful effect that we've seen now in people that we have in ongoing study with subretinal. And that led us to look at a whole -- scan a whole spectrum of different delivery device options and the suprachoroidal device was something that preclinically continued to be appealing because it showed a consistent safety profile that didn't involve things that we expect to see in humans. We're looking forward to advancing that and dosing patients with suprachoroidal system in collaboration with Clearside. We've been finalizing the work that we feel like we need to do to be able to launch that and get these new filings on. And so we'll be able to prove that correlation between the preclinical safety profile and the human safety profile in the second half of this year. In the meantime, we continue to be very assertive about advancing the subretinal program because we view that the type of profile of improvement and sort of advantage that the subretinal approach has continues to be, in our view, the most unique application of VEGF inhibition with a onetime administration and the level of pharmacological rigor that we've taken to put into the most number of patients at this point in the study.

Okay. That's very helpful. Just quickly, I wanted to ask, since you mentioned suprachoroidal delivery, if initial data looks very impressive, how would you decide between suprachoroidal delivery versus the subretinal? Will you still move forward with subretinal?

Yes. I mean if you look at our time lines and our plan, we have a few more months to go to read out the 12-month data on Cohort 5. We're already gearing up the plan for filing an initiation of the pivotal study for subretinal. In the case of evaluation of the suprachoroidal procedure, incredibly encouraged about the preclinical data, but we still need to see the human data to understand what we're working with from a product profile perspective. Now the beginning of that will read out for us later this year, at which point we'll already have meaningfully started the enrollment and expansion of the pivotal study for subretinal. So there's no doubt to us that the subretinal approach and the profile of data that we have, the application -- the type of data that we're seeing and the benefit that it can provide patients is absolutely on track to advance in a way that we'll have the opportunity to get to market fastest. And I think for the suprachoroidal approach, there's no reason to make a decision about either/or. We view that this market for VEGF inhibition, if you step back and look at it overall, look at the number of interventions and companies and sort of improvements that people are trying to make just on the base case of inhibiting VEGF, that really -- there's an opportunity for us to have multiple procedures with the pharmacology of RGX-314 that just expand our footprint for REGENX in wet AMD overall. But we also need to establish what suprachoroidal is in vivo in human. And that's -- in 2020, that's the value expansion that we're looking to occur for the pharmacology of RGX-314.

Okay. Very helpful. So for the subretinal pivotal study, you did mention that, in the past, there likely will be 1 year change in visual acuity versus standard of care. Just wondering how would the visual acuity be [ counted ] for those patients who have to take a rescue injection?

Yes. So -- I mean the actual measure of visual acuity would be read the same way. I think you're talking about the possibility, if not the likelihood, that we end up with sort of a sub-spectrum of patients who may have received an injection over the course of, let's say, 9 months or a year and what impact that might have on that local visual acuity measure that we use as the primary end point. I think in that case, that's going to be something that will be a consideration based on the data and the likelihood of the influence or effect of when that injection occurred. Obviously, an injection that occurs, perhaps, for some reason, early on in the evaluation of a patient, let's say, 2 or 3 months versus something that occurred at or near to the visit that was coincident with the primary end point would be interpreted both by scientists, clinicians, regulators to have a very different effect. But I think this is something that we're expecting and are going to be familiar with it. There will be a most enriched population of patients that we will have sort of the clearest perspective in view of what BCVA is without receiving any injection, like we have in the 3 cohorts that are showing clinically meaningful response right now in the current study. And others, I think, will make meaningful contributions as well overall to the assessment of the product and its potential for both registration and use. So I think that some of the evidence that I think is going to be a real benefit from a program like this overall is sort of assessing its real-world use and some of the real-world evidence. We do not expect that gene therapy is the answer for all patients in wet AMD and that every patient that receives RGX-314 upfront will never see another injection again. We do think that the benefit of an approach like this is that for some patients it will, for years, require them...

Excuse me. This is the operator. The presentation is about to end.

We still have 1 minute. Thank you.

Sorry, Gena. So I think that, that stratified data set is going to be incredibly valuable. And there certainly will be -- the design of the study will be powered and structured in a way that all the different data will, we think, contribute to the potential approvability.

Okay. And for the suprachoroidal Phase I, what kind of steroids regimen you will be thinking? The prophylactic treatment, will you be also including oral or topical?

No. We don't currently use any steroid treatment in the subretinal procedure approach, and we don't expect to in the suprachoroidal approach either.

Okay. So even right at the beginning for the patient that -- taking virus?

That's right. Yes, that's not -- we don't use that in subretinal, and we don't expect to use that in suprachoroidal either.

Okay. Okay. And then just quickly wanted to ask about MPS II program. I think that you showed -- in your interim data, you showed heparan sulfate reduction 33% at the week 8 from 3 patients. How much do we know regarding the CSF heparan sulfate reduction in neurocognitive improvement? And what is your goal of HS reduction?

Yes. I mean our goal is to get as much reduction as we can. We know that in MPS -- MPS I and II, III and VII all have known correlation and good relationship between heparan sulfate and neurocog. In MPS II, there's actually some of the best natural history data on that topic, even more so than the others. And so we want to see further reductions at a higher level dose. We do believe that they will, if they're consistent and sustained, will be correlative to neurocog stability and improvement against natural history overall. So we chose MPS I and MPS II as our primary programs in this neurodegenerative space because of the contributions that biomarkers and other outcomes can make to the potential approvability of these products. What's known in the natural history because of existing drugs and the prevalence of patients is a major contributor to that.

Great. And last question quickly regarding manufacturing for your Rockville field, the 2021 completion. Once they complete, what is the capacity you will have with the new headquarter?

Yes. I mean the idea is that we will have full scale, flexible, large GMP facility up to 2,000 liter bioreactors and up to 2 trains that will feed the ability to also do final fill and finish. And so this is a significant facility that will be adjacent to our research and development and process development labs that exist.

Great. Thank you very much, Ken.

Thanks, Gena, thanks, everyone. Have a good day.

Thank you. This concludes our call.