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Edited Transcript of RGNX.OQ earnings conference call or presentation 4-Nov-20 9:30pm GMT

·34 min read

Q3 2020 Regenxbio Inc Earnings Call Rockville Nov 5, 2020 (Thomson StreetEvents) -- Edited Transcript of Regenxbio Inc earnings conference call or presentation Wednesday, November 4, 2020 at 9:30:00pm GMT TEXT version of Transcript ================================================================================ Corporate Participants ================================================================================ * Kenneth T. Mills REGENXBIO Inc. - CEO, President & Director * Patrick J. Christmas REGENXBIO Inc. - Chief Legal Officer * Stephen Pakola REGENXBIO Inc. - Chief Medical Officer * Vittal K. Vasista REGENXBIO Inc. - CFO ================================================================================ Conference Call Participants ================================================================================ * Alec Warren Stranahan BofA Merrill Lynch, Research Division - Associate * Gbolahan Amusa Chardan Capital Markets, LLC, Research Division - Director of Research & Head of Healthcare Research * Huidong Wang Barclays Bank PLC, Research Division - Research Analyst * Konstantinos Biliouris Morgan Stanley, Research Division - Research Associate * Lisa A. Walter RBC Capital Markets, Research Division - Associate * Matthew Kelsey Harrison Morgan Stanley, Research Division - Executive Director * Rick Stephen Bienkowski SVB Leerink LLC, Research Division - Associate ================================================================================ Presentation -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- Good afternoon, and welcome to the REGENXBIO Third Quarter 2020 Earnings Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded. I would now like to turn the call over to Mr. Patrick Christmas, Chief Legal Officer for REGENXBIO. You may begin. -------------------------------------------------------------------------------- Patrick J. Christmas, REGENXBIO Inc. - Chief Legal Officer [2] -------------------------------------------------------------------------------- Good afternoon, and thank you for joining us today. With us today are Ken Mills, REGENXBIO's President and Chief Executive Officer; Dr. Steve Pakola, our Chief Medical Officer; and Vit Vasista, our Chief Financial Officer. Earlier this afternoon, REGENXBIO released financial and operating results for the third quarter ended September 30, 2020. The press release reporting our financial results is available on our website at www.regenxbio.com. Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend and other words of similar meaning. Any such forward-looking statements are not guarantees of future performance and involve certain risks and uncertainties. These risks are described in the Risk factors and the management's discussion and analysis section of REGENXBIO's annual report on Form 10-K for the full year ended December 31, 2019, and comparable risk factors sections of REGENXBIO's quarterly reports on Form 10-Q, which are on file with the Securities and Exchange Commission and available on the SEC's website. Any information we provide on this conference call is provided only as of the date of this call, November 4, 2020, and we undertake no obligation to update any forward-looking statements we may make on this call on account of new information, future events or otherwise. Please be advised that today's call is being recorded and webcast. In addition, any unaudited or pro forma financial information that may be provided is preliminary and does not purport to project financial positions or operating results of the company. Actual results may differ materially. I would now like to turn the call over to Ken Mills. Ken? -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [3] -------------------------------------------------------------------------------- Thank you, Patrick. Good afternoon, everyone. Thanks for joining us. I hope everyone is staying healthy. On today's conference call, we will provide a recap of our recent progress advancing and expanding our NAV technology platform as well as expected future milestones, Steve will provide an update on our clinical programs, and Vit will provide an update on financial results from the third quarter 2020. We'll then open up the call for questions. I'm proud to say that during this quarter, we've hit several milestones in development of our internal clinical pipeline as 2 important Phase II studies evaluating RGX-314 when delivered in the suprachoroidal space are now underway for the treatment of wet AMD and diabetic retinopathy. And we've expanded our MPS II program to include additional patients in the ongoing Phase I/II study of RGX-121. In addition, our partners at Novartis have recently achieved significant milestone in the gene therapy space with over $1 billion in cumulative net sales of ZOLGENSMA, a transformative onetime gene therapy for the treatment of pediatric patients with spinal muscular atrophy and the first approved gene therapy based on REGENXBIO's NAV technology platform. We're grateful to have contributed to a therapy that's impacted the lives of over 700 children with SMA and their families around the world. As always, we remain focused on the health and safety of our employees, partners and patients during this challenging COVID-19 pandemic. We continue to actively monitor the impact that pandemic will have on our plans for preclinical and clinical development time lines, and we're focused on our general operations for the remainder of 2020 and into 2021. With that, I'd like to turn the call over to Steve for a more detailed clinical and regulatory update. -------------------------------------------------------------------------------- Stephen Pakola, REGENXBIO Inc. - Chief Medical Officer [4] -------------------------------------------------------------------------------- Thanks, Ken. We've been focused on development plans for the RGX-314 program with several studies underway in wet AMD and diabetic retinopathy and the start of the pivotal program to come. We believe that RGX-314 has the potential to profoundly impact all aspects of clinical management for patients with wet AMD and DR and could be a onetime gene therapy treatment option for a broad range of patients. Our plans for the pivotal study for the subretinal delivery of RGX-314 for the treatment of wet AMD, including dose selection, number of patients and other factors are based on the learnings from the first-in-human ongoing Phase I/II study, including results from patients in cohorts 3, 4 and 5. As previously shared, these patients have demonstrated stable-to-improved visual acuity and retinal thickness as well as a meaningful reduction in anti-VEGF injection burden. We also have data from cohort 3 out to 2 years, which gives us confidence in long-term durability of the gene therapy. We now expect to initiate our pivotal program for the subretinal delivery of RGX-314 for the treatment of wet AMD in the first quarter of 2021 and look forward to providing more details for this study in the coming months. In September, we announced the dosing of the first patient in the Phase II AAVIATE trial, evaluating the suprachoroidal delivery of RGX-314 using the SCS Microinjector for the treatment of wet AMD. The initiation of this trial was an important milestone for our company as well as the field as the first clinical trial to evaluate the delivery of any gene therapy to the suprachoroidal space. We are excited about the potential of the targeted in-office suprachoroidal approach, which may provide additional RGX-314 delivery options for patients beyond subretinal delivery. Importantly, patients in this trial will not receive prophylactic immunosuppressive corticosteroid therapy before or after administration of RGX-314. To date, RGX-314 has been well tolerated, including no evidence of inflammation. We remain on track to complete enrollment of the first cohort by the end of 2020 and report initial safety data from the first cohort in early 2021. Our Phase II trial, ALTITUDE to evaluate suprachoroidal delivery of RGX-314 in patients with diabetic retinopathy is active, and we expect to begin enrolling patients by the end of 2020. DR is the leading cause of blindness in working-age adults and affects approximately 8 million Americans. As the disease progresses from nonproliferative disease, a stage in which patients are often asymptomatic, to more severe disease, patients are at increased risk of developing vision-threatening complications. Most patients with nonproliferative DR often go untreated as the current standard of care is watchful waiting until vision becomes threatened. There are treatment options for patients with DR, including chronic repeated anti-VEGF injections, retinal laser treatment and surgery. However, receiving frequent anti-VEGF intraocular injections makes the treatment a less desirable option versus watchful waiting for many asymptomatic DR patients. Unfortunately, without treatment, a large proportion of these patients will eventually develop vision-threatening complications, including diabetic macular edema and neovascularization that can lead to blindness. We believe that onetime treatment with RGX-314 has the potential to provide sustainable, long-term anti-VEGF delivery, reducing severity of DR and preventing vision-threatening complications. The ALTITUDE trial is expected to enroll 40 patients with DR across 2 dose cohorts. Patients will be randomized to receive RGX-314 versus observational control at a 3:1 ratio. The primary endpoint of the study is change in diabetic retinopathy severity based on the ETDRS DRSS scale at 48 weeks, a scale well-known to regulators and was actually used for approval of EYLEA and Lucentis for the treatment of DR indication. Other endpoints include safety and development of diabetic retinopathy-related complications. We expect to begin dosing patients across 15 leading U.S. retina centers by the end of 2020 and plan to report interim data from this trial in 2021. Turning to our rare disease portfolio. In September, we announced the expansion of the RGX-121 program for the treatment of MPS II, including an amendment to our ongoing Phase I/II study to allow for additional patients in an expanded cohort 2. We are excited to announce that we have already dosed 2 more children in this cohort, and we anticipate further updates from this trial by the end of 2020. In addition, we plan to initiate a second Phase I/II multi-center open-label trial to evaluate RGX-121 in older pediatric patients with severe MPS II. We have plan to enroll up to 6 patients and administer RGX-121 directly to the cerebrospinal fluid through intracisternal or intracerebroventricular injection. We also announced our plans to initiate a new observational trial designed to provide detailed characterization of neurocognitive development and key biomarkers in patients with severe MPS II. In severe forms of MPS II, early developmental milestones in a child may be met, but delays become apparent by 18 to 24 months with neurologic deficits and cognitive impairment becoming apparent by the age of 6 years. This trial is intended to prospectively document the changes in neurodevelopmental parameters of cognitive, behavioral and adaptive function over time in addition to biomarker activity in the CSF, serum and urine. We believe the study will provide critical data about the neurocognitive development of young pediatric patients with MPS II. And we look forward to sharing the data from this observational study with the patient community. We, of course, have a number of additional programs headed towards the clinic and I look forward to 2021 being a key year for development, advancement of these gene therapy candidates, particularly within our rare disease pipeline. Notably, our programs for CLN2 disease, RGX-181, which is designed to address the CNS manifestations and RGX-381, which is designed to address the ophthalmic manifestations of the disease, are on track for IND filing in the coming months. We look forward to initiating clinical trials for both these programs. With that, I turn the call back over to Ken. Ken? -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [5] -------------------------------------------------------------------------------- Thanks, Steve. We're obviously very encouraged by the progress and the focus on the internal pipeline and the work by the entire team. And congrats again, Steve, on the acquisition of the new puppy. -------------------------------------------------------------------------------- Stephen Pakola, REGENXBIO Inc. - Chief Medical Officer [6] -------------------------------------------------------------------------------- Thank you. -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [7] -------------------------------------------------------------------------------- So we have a couple of things to highlight in addition to the internal program work this quarter. And as we know, REGENX has an extensive footprint in the gene therapy space. Our NAV vector is the basis of work not only internally, but also many partnered product candidates and including 1 marketed product, Novartis' ZOLGENSMA, as well as several others that are in late-stage clinical development. Our team recently collaborated with Kurma Partners, a leading European venture capital firm, to form Corlieve Therapeutics, a new company focused on severe neurological conditions. And under the collaboration and license agreement with the newly formed Corlieve, we have received equity as well as are eligible to receive milestone payments and royalties in return for their use of the NAV AAV9 vector for the treatment of refractory temporal lobe epilepsy. In addition, Olivier Danos, our Chief Science Officer, has joined Corlieve's Board of Directors and will work closely with the team on the development of the TLE program. So we're encouraged by this new development in our pipeline. And also, I wanted to highlight that, as I mentioned earlier, great progress this quarter and throughout the year so far on ZOLGENSMA. As announced last week in our press release, REGENXBIO has received a milestone payment of $80 million from Novartis based on the achievement of over $1 billion in cumulative net sales of ZOLGENSMA. We're strongly encouraged by the therapy's strong global momentum and its potential to help many more patients and families. So with that, I'll turn the call over to Vit, and he can review the financials. -------------------------------------------------------------------------------- Vittal K. Vasista, REGENXBIO Inc. - CFO [8] -------------------------------------------------------------------------------- Thank you, Ken. REGENXBIO ended the quarter on September 30, 2020, with cash, cash equivalents and marketable securities totaling $289.8 million compared to $400 million as of December 31, 2019. The decrease was primarily attributable to net cash used in operating activities of $93.5 million and cash used to purchase property and equipment of $14 million. Cash reported as of September 30, 2020 excludes the recently announced $80 million milestone payment received from Novartis in October 2020, which was recorded as accounts receivable at the end of the third quarter. Revenues were $98.9 million for the quarter ended September 30, 2020 compared to $14.7 million for the third quarter of 2019. The increase was primarily attributable to $9.6 million increase in ZOLGENSMA royalty revenue over Q3 2019 and the onetime $80 million milestone fee recognized as revenue in the third quarter of 2020 on the achievement of $1 billion in cumulative net sales of ZOLGENSMA since launch. Sales of ZOLGENSMA for the third quarter of 2020 increased by 82% as compared to Q3 2019. Research and development expenses were $44 million for the quarter ended September 30, 2020 compared to $35.7 million for the third quarter of 2019. The increase was primarily attributable to personnel-related costs as a result of increased headcount, expenses associated with conducting clinical trials for our lead product candidates and externally sourced services for preclinical, regulatory and manufacturing-related activities. G&A expenses were $15.9 million for the quarter ended September 30, 2020 compared to $12.4 million for the third quarter of 2019. The increase was primarily attributable to personnel-related costs as a result of increased headcount and professional fees for advisory and other services. Net income was $8.8 million or $0.24 basic and $0.23 diluted net loss per share for the 3 months ended September 30, 2020 compared to a net loss of $34.6 million or $0.94 basic and diluted net loss per share for the 3 months ended September 30, 2019. As of September 30, 2020, we had approximately 37.4 million common shares outstanding. Based on its current operating plan, REGENXBIO expects its balance in cash, cash equivalents and marketable securities as of September 30, 2020 in addition to the $80 million received from Novartis in October 2020 to fund its operations, including the completion of its internal manufacturing capabilities and clinical advancement of its product candidates until mid-2022. With that, I will turn the call back to Ken to provide final thoughts on yesterday's results. -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [9] -------------------------------------------------------------------------------- Thanks, Vit. A really good summary of the financial condition of the company and on top of Steve's updates about the program work as well as the encouraging developments with our partners, again it continues to be a good time for REGENX to be advancing value for patients and stakeholders. And I also wanted to highlight that the construction of our new GMP facility here in Rockville continues, a facility that allows us to manufacture 2,000-liter scale using fully optimized HEK293 suspension cell culture system. This is a platform that is widely utilized and is also well understood by the regulatory agencies. So we continue to make substantial improvements in our efforts to ensure consistency of products across large volumes and across multiple programs. And in all, this has been a multiyear effort led by a great team of people that have both commercial level expertise in biologics as well as gene therapy and a global supply chain experience that emphasizes high quality, well-characterized scalability to match the clinical and emerging commercial demands of REGENXBIO. So we're excited about that progress and look forward to the site coming online. And in general, we look forward to making more strides towards our mission to improve lives through the curative potential of single-administration gene therapies, and we remain dedicated to this mission. I want to definitely take time to express the sincere appreciation that myself and the leadership team have to our talented and dedicated employees who are driving business forward despite the challenging backdrop of the COVID-19 epidemic. With that, operator, we will turn the call over to questions. ================================================================================ Questions and Answers -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- (Operator Instructions) Our first question comes from the line of Gena Wang with Barclays. -------------------------------------------------------------------------------- Huidong Wang, Barclays Bank PLC, Research Division - Research Analyst [2] -------------------------------------------------------------------------------- So I have 2 questions. First set of questions regarding the suprachoroidal microinjector program, AAVIATE trial in wet AMD. So you mentioned that you already dosed the patients. Just wondering how many patients have already been dosed, and is that right all the patients you have dosed, so far you haven't seen any inflammation in this patients? And then related question is regarding the safety data in the first quarter next year. Beyond the safety, I assume it will be 3 patients from cohort 1. Will you also show biomarker data and initial efficacy data, including rescue injection and visual acuity and OTC? And the second question is regarding the MPS II. Just wondering if you can give a little bit more color regarding the year-end '20 update, what type of data in terms of also patient numbers and type of data that we will see? -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [3] -------------------------------------------------------------------------------- Gena, thanks for the question or questions. And Steve, maybe I'll ask you to provide an update on AAVIATE, just what we've seen so far and what we're thinking about for early 2021. -------------------------------------------------------------------------------- Stephen Pakola, REGENXBIO Inc. - Chief Medical Officer [4] -------------------------------------------------------------------------------- Sure. Gena, thanks for the questions. Yes. So AAVIATE, as we disclosed today, and as you mentioned, it is true that we've not seen any evidence of inflammation so far. It is still early in the trial in terms of number of patients treated. You also asked that question. We only did just announce the dosing of the first patient in early September, so not that long ago and as is typical for an initial study with, albeit not a first-in-human study for RGX-314, this study is a first-in-human for delivery to the suprachoroidal space. That was actually a sentinel subject where we initially dose it and follow for a couple of weeks, in general, to follow for overall safety and then proceed with dosing of the rest of the cohort. And we, of course, were able to do that as we've announced that we've seen no inflammation in any of the patients that we've dosed to date. We have a total of 20 patients that we want to dose in cohort 1, 15 of which will receive RGX-314. We've dosed multiple patients, but we're still early in the game as far as activating all the sites and really ramping up recruitment and that's one of the key reasons that we're not in a position to give, for example, a more fulsome update and why, as you mentioned, we'll be giving our true initial safety update early next year. But certainly, we're encouraged by the fact that in spite of having no immune suppression at all in terms of, for example, no topical steroids before or after RGX-314, to date, we're not seeing inflammation. And that's what we were able to achieve preclinically. But this being not a subretinal space, this being the first study ever looking at gene therapy in the suprachoroidal space, this is really a significant milestone in terms of assessing safety and tolerability and importantly, whether we can achieve with AAV8 delivery, specifically with RGX-314, the ability to deliver without immune suppression therapy and without inflammation. So the second part of your question in terms of what we can expect to provide in that initial safety update early in 2021. I guess, fairly to manage expectations, it will be a few more months on and we'll have a full cohort of patients that we're guiding since we still plan to complete recruitment of the 20 patients in that first cohort. And in that first update, as part of the overall assessment, certainly, we continue to look at safety and tolerability first, as always, but also be able to provide some of the typical biomarker or pharmacodynamic activity measures that we've traditionally provided for our subretinal program, though again, we caution it's still pretty early in terms of number of months that patients have been treated. And I think we've been consistent all along for several years now in how we've talked about pharmacodynamic measures and the importance of looking at durability of treatment effect where you really want to be able to look at, for example, 6 months of data -- so before you really have a sense there. So nevertheless, we still, in that initial safety update would be including some of those typical assessments, even just from a safety perspective. -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [5] -------------------------------------------------------------------------------- Yes. And just quick -- thanks, Steve, for the complete answer there. And on MPS II, Gena, just quickly, we do have plans for an update before the end of this year. And very pleased to have announced today 2 additional patients enrolled at the 6.5E10 dose level under this expanded protocol. What we have is plans for updating the data set of patients that have been previously enrolled and pulling those time lines forward a bit more. So we'll be looking to do that in the next couple of months. -------------------------------------------------------------------------------- Operator [6] -------------------------------------------------------------------------------- And our next question comes from the line of Geoff Meacham with Bank of America. -------------------------------------------------------------------------------- Alec Warren Stranahan, BofA Merrill Lynch, Research Division - Associate [7] -------------------------------------------------------------------------------- This is Alec on for Geoff. So my first question is on 314. Do you have a sense from your physician interactions what an acceptable frequency of rescue VEGF injections would be with 314 for clinical adoption, particularly taken into account the 3-month dosing for Beovu and 6 months for Lucentis PDS. I know it may be a bit premature considering 314 just started pivotal study or will early next year, but would you also be able to provide your thoughts on reimbursement discussions and how those are evolving for gene therapies and whether payers would also be looking at the rate of rescue injections to make reimbursement decisions? -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [8] -------------------------------------------------------------------------------- Sure. Steve, I'll let you swing back to maybe some of the physician interaction in terms of intervals of treatment. Alec, thanks for the question. I mean we have -- we're moving into a pivotal phase of development, and we have started to engage the entire system in discussions about the value and need around changes in standard of care for wet AMD and a lot of receptivity to not just extending, but eliminating the intervals that exist around treatment in terms of compliance and convenience. So I think we continue to view that gene therapy has a unique profile, that has a tremendous amount of value and really emphasize at this moment in time where this overhang of pandemic is really affecting and influencing, I think we're hearing from people both on the care side as well as on the provider and reimbursement side what is happening to people right now, if they're not able to come in and get their regular treatments and how much more effect is that going to have on outcomes and ultimately, on cost and productivity and other things. So a lot of people paying attention right now. And through that engagement, I think the profile that we've had for a while has been to get at least half of the injections worldwide eliminated. We've talked about this as our target product profile, taking a look at what the market is today for VEGF injection rates. And it hasn't moved all that much with respect to changes in labeling. I think when you look at the clinical data, when you look at the sort of chronicity of how things like Lucentis and EYLEA and Beovu and maybe what's to come or coming forward, hasn't moved the needle all that much. We need to be doing more, and that's where we're focused on that unmet need. In terms of where that value lands ultimately, I think it's for a onetime treatment or one that has seen dramatic reduction, 50% or more in the use of existing therapy or therapies that are emerging that are incremental, we view a huge opportunity there and have been very pleased with the conversations and the responsiveness that we've been able to engage so far at the stakeholder level there. Steve, maybe you can talk to clinically what the engagement's been like? -------------------------------------------------------------------------------- Stephen Pakola, REGENXBIO Inc. - Chief Medical Officer [9] -------------------------------------------------------------------------------- Yes. It's been very interesting, and you raised a good point, Ken, on the COVID impact and how that's really shined a light on the importance of durability and ultimately, the possibility of a onetime treatment. And we're hearing that anecdotally, not only for the patients in our ongoing study, who fortunately have been able to have the need for reinjection eliminated where we've seen real-time patients in surge areas who've been able to miss a visit or 2, which we don't like from a clinical trial standpoint, but from an overall benefit/risk, the ability to have the comfort that you have the foundational anti-VEGF treatment that you need, and you're not risking potentially vision-threatening complications by extending your visits. And it really comes back to how these physicians and their patients and their caregivers evaluate the benefit/risk. And you raised Beovu and PDS and, as you know, retina's a dynamic space, and it's been a dynamic space. So we've known about these programs for a while and that target product profile that Ken reviewed of at least 50% reduction, either looking in terms of treatment burden or even looking in terms of patients who can completely have need for reinjections done away with, that hasn't changed in our minds because it hasn't changed in the minds of the investigators and our retina, the specialist advisers and their view of what's needed for their patients. And it's interesting, we don't really think of any of these welcomed advances in terms of these approved and other experimental agents that are able to advance to durability intervals of 3 to 4 months or 5 months or even 6 months as competition. If anything, these are clear validation of how much need there is to get more durable, sustainable treatments. And the ultimate way to do that would be a onetime injection. So we continue to see this as further validation for a onetime treatment and continue to see support for the target product profile that Ken elaborated on. -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [10] -------------------------------------------------------------------------------- And remember, we feel that with the work we've already done in the assessment of subretinal at multiple dose levels, we have outperformed that target product profile and in a very challenged and severe population of patients. So we're feeling very good about the progress and the data set there as we're funneling it into a pivotal phase of development and also looking to differentiate the profile with suprachoroidal. So thanks, Alec, for the question. -------------------------------------------------------------------------------- Operator [11] -------------------------------------------------------------------------------- Our next question comes from the line of Gbola Amusa with Chardan. -------------------------------------------------------------------------------- Gbolahan Amusa, Chardan Capital Markets, LLC, Research Division - Director of Research & Head of Healthcare Research [12] -------------------------------------------------------------------------------- I have 2 questions. The first is on manufacturing, given that you have internal coming online, which people recognize have certain advantages. But we've also heard that it's not just having a facility or footprint, it's the processes, analytics. So could you talk about what you're doing to sort of have a best practice on those dimensions or anything you may be doing to avoid some of the growing pains that we've seen in the AAV-based gene therapy space with regards to manufacturing? -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [13] -------------------------------------------------------------------------------- Yes, Gbola, thanks a lot. I'm glad you went there because it's a -- well, I think it previously has been a subtle but maybe less and less subtle point for investors on these areas. And I would say that even with our existing supply chain and the strong collaborations we have with bulk manufacturers and final fill-finish with groups like FUJI and others, we have installed capabilities here in Rockville already in labs for analytics, quality assurance, quality control, assessment, release criteria that relate to not only the AAV side of the equation, but let's not forget about the device and route of administration side here. We're working with subretinal procedures, we're working with suprachoroidal procedures, we're working with intracisternal procedures and intravenous procedures. So we have compatibility with all of the devices that are being sent to these sites clinically and commercially as well. And that's been a major focus of quality, of sort of strong analytical capabilities, assessing things across wide range of different types of AAV vectors when it comes to things like potency as well has been really important to have that expertise internally. And that's already here. So in some ways, what we're actually bringing further into Rockville, in our view, is more of the commodity scale things that we need to take the next steps in terms of insulating ourselves with respect to -- especially that commercial supply chain risk. But we think that we have a really strong foundation in a lot of those other areas that, as you pointed out, I think, have been stumbling blocks and certainly can be, especially in a new and emerging area of science and manufacturing science. -------------------------------------------------------------------------------- Matthew Kelsey Harrison, Morgan Stanley, Research Division - Executive Director [14] -------------------------------------------------------------------------------- Our next question comes from the line of Matthew Harrison with Morgan Stanley. -------------------------------------------------------------------------------- Konstantinos Biliouris, Morgan Stanley, Research Division - Research Associate [15] -------------------------------------------------------------------------------- This is Kostas on for Matthew. I have a quick question on your CLN2 programs. Can you please talk about the status of the programs and what needs to be done before you file for the IND in 2021? -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [16] -------------------------------------------------------------------------------- Sure, Kostas. Just at a high level, I'll see if Steve has anything else to add, we're guiding here to milestones that are very soon with respect to those 2 programs. So in the case of both, we are really having completed the preclinical study evaluation phase and readout phase and keeping in mind that certain things like the 181 program, in particular, is borrowing also from existing IND and ongoing study packages from things like 121, for instance, we're really translating that right now into written word and the modules of the IND filing. And similarly, for RGX-381, we're using route of administration that we're familiar with. We've already highlighted that we've reported data from nonhuman primates demonstrating sustained levels of things like the enzyme TPP1 in vitreous following a subretinal injection. So similarly, we're in a phase right now here at the beginning of November to be filing an IND by the end of the year. We're literally in the final phases of preparing the reports and writing the documents to be submitted. I hope that helps. -------------------------------------------------------------------------------- Operator [17] -------------------------------------------------------------------------------- Our next question comes from the line of Mani Foroohar with SVB Leerink. -------------------------------------------------------------------------------- Rick Stephen Bienkowski, SVB Leerink LLC, Research Division - Associate [18] -------------------------------------------------------------------------------- This is Rick dialing in for Mani. So now that the pivotal 314 trial is set to start in the first quarter of 2021, we were hoping to get some color on the trial design. Have you received any feedback from the FDA regarding the pivotal endpoints, what the control arm would look like, duration of endpoints or any other aspect of trial design? -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [19] -------------------------------------------------------------------------------- Rick, thanks. No, not that we're updating today, and we will plan to update that at the beginning of next year when we talk about the initiation of the study. So we continue to guide to the fact that we think moving into pivotal phase of development in retina has some familiarity with the agency for different types of products, different types of modalities, things that have already been brought up on this call, of course, like recently, Beovu and, of course, PDS and so forth. So we're not expecting people to be surprised here with some massive departure in certain ways with respect to how things are considered at FDA when it comes to wet AMD and retina. However, there's obviously a gene therapy event to it and an RGX-314 event as well. And we definitely will come forward clearly with more details on that study design early next year. And Steve, anything else to add at this stage? -------------------------------------------------------------------------------- Stephen Pakola, REGENXBIO Inc. - Chief Medical Officer [20] -------------------------------------------------------------------------------- No, you've covered it nicely. We're excited to move into this stage. And yes, we're about there. -------------------------------------------------------------------------------- Operator [21] -------------------------------------------------------------------------------- (Operator Instructions) And our next question comes from the line of Lisa Walter with RBC Capital Markets. -------------------------------------------------------------------------------- Lisa A. Walter, RBC Capital Markets, Research Division - Associate [22] -------------------------------------------------------------------------------- This is Lisa Walter on the line for Luca Issi at RBC. We just wanted to ask if we could have an update on the IP dispute going on between you and Passage Bio as well as Sarepta. -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [23] -------------------------------------------------------------------------------- Lisa, thanks a lot. We don't have any specific updates to provide today. We have provided information previously on -- or I guess, provided feedback with respect to our interest in making sure that people that are working with intellectual property and science that overlaps with our NAV technology platform are under license so that they're free to do so, but also fairly representing what they're doing with respect to their science and that we're looking out for the interest of what we think, not only our shareholders and stakeholders, but the interest of IP in general, in our biotechnology space overall. And that also tends to be groups that we view that are getting closer to commercialization sort of come up higher, if you will, on our radar screen with respect to sort of action and interest that we have overall. So nothing more specific to update on today other than that's our philosophy. We think it's an important one to be not only reflecting that we are and view IP as important as an industry and as a field in gene therapy, but also specifically for our shareholders. And hope to have more updates on those actions coming into 2021 and throughout the year. Thanks for the question. -------------------------------------------------------------------------------- Operator [24] -------------------------------------------------------------------------------- And we have a follow-up question from the line of Gbola Amusa with Chardan. -------------------------------------------------------------------------------- Gbolahan Amusa, Chardan Capital Markets, LLC, Research Division - Director of Research & Head of Healthcare Research [25] -------------------------------------------------------------------------------- And this one, first of all, congrats on the $80 million payment on ZOLGENSMA. I get asked a lot about how long I should model the royalties from Novartis. So I've noticed that you do have patent term extension and supplementary protection certificates as a process ongoing in multiple jurisdictions, given additional approvals. Would you say we analysts should think of those as relevant to the duration of the royalty payments? Or are they less relevant? What can you say? What's the 101 on them? -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [26] -------------------------------------------------------------------------------- Gbola, thanks. 101, I like that, AVXS-101. That was clever. The work that we're doing around patent term extension, I think -- I mean all of you in the -- on the sell side, I think, understand much about the processes on the biologics side, in particular. We have approvals now that are occurring. It started in the U.S. and now is carried over into other jurisdictions in Europe and Japan. And so the process of filing for patent term extension for keeping in mind that our -- as we've always discussed, but just to reemphasize, the NAV technology platform and the patents that underpin the compositions and the methods of use and so forth that fall under our licenses are worldwide, right? And they have issued claims in all the jurisdictions. So we follow through with the pursuit of patent term extension at sort of normal course in each one of those jurisdictions on an individual or case-by-case basis as they're approved. And similarly, our license, in this case, with AveXis, I guess, Novartis' gene therapy now, as we amended and expanded it, it includes license to a lot of patents in our portfolio relating to ZOLGENSMA and AVXS-101. The norm is to file and get feedback and manage the process for potential to extend in many jurisdictions up to 5 years. We've guided that with respect to how quickly ZOLGENSMA got approved in the U.S., the likelihood of extending or the possibility of extension is actually curved a bit and it's going to be closer to, I think, somewhere between 3 and 4 years. But we think it is entirely appropriate to be following that process, expecting that it occurs, similar in nature to how biotechnology and biological products, existing products have had patents extended to protect them and that 3 years in the U.S. or more and up to 5 years in jurisdictions like Europe and Japan are appropriate to consider based on how the license is structured, the type of IP that's being provided to protect ZOLGENSMA and the value in it for us and Novartis gene therapy. -------------------------------------------------------------------------------- Operator [27] -------------------------------------------------------------------------------- And I'm showing no further questions at this time. And I would like to turn the conference back over to Mr. Ken Mills for any further remarks. -------------------------------------------------------------------------------- Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [28] -------------------------------------------------------------------------------- Okay. Thank you, operator. Thanks, everyone, for the questions. Most importantly, I hope everyone is safe, healthy and well. It's been an interesting year, and we definitely will be in touch with everyone between now and the end of the year with more updates and milestones as we've guided to as well as some conferences that are coming up and really excited to transition from 2020, maybe with the new outlook in general, but positive nonetheless. We've accomplished a lot in 2020. Coming into 2021, we look to continue to build on that. And again, appreciate all the questions. Appreciate the listening. I hope everyone's well, and have a great evening. -------------------------------------------------------------------------------- Operator [29] -------------------------------------------------------------------------------- Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect. Everyone, have a great day.