Good afternoon and welcome to the REGENXBIO First Quarter 2019 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will be given at that time. As a reminder, this conference call is being recorded. I would now like to turn the call over to Mr. Patrick Christmas, Senior Vice President and General Counsel for REGENXBIO. You may begin.

Good afternoon and thank you for joining us today. With us today are Ken Mills, REGENXBIO's President and Chief Executive Officer; Steve Pakola, our Chief Medical Officer and Vit Vasista, our Chief Financial Officer. Earlier this afternoon, REGENXBIO released financial and operating results for the 3 months ended March 31, 2019. 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 sections of REGENXBIO's filings with the Securities and Exchange Commission which are available on the SEC's website. Any information we provide on this conference call is provided only as of the date of this call May 7, 2019 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, President and Chief Executive Officer of REGENXBIO.

Thank you, Patrick, and good afternoon everyone and thanks for joining us. On today's conference call, we will provide a recap of our recent progress in the advancement of our NAV Technology Platform and the continued progress of our internal product candidates. Steve will provide an update on our clinical programs and Vit will provide an update on financial results for the first quarter of 2019. At the end, we'll open the call for questions. At REGENXBIO, our mission is clear. We seek to improve lives through the curative potential of gene therapy based on our proprietary NAV Technology Platform. We believe single administration gene therapy treatments can significantly alter the course of genetic diseases and diseases broadly affecting public health and we are committed to our research and development of gene therapies with patients in mind. Our NAV Technology Platform consists of over 100 novel adeno-associated viral vectors or AAV vectors including AAV7, AAV8, AAV9 and AAVrh10. REGENXBIO's novel and unique approach to gene therapy focuses on enabling cells in the body to produce therapeutic proteins or antibodies and targeting and correcting genetic defects. Our product candidates have the potential to change the course of the disease and deliver improved patient outcomes in therapeutic areas where significant unmet medical needs remain and they're designed to provide long-lasting clinical benefit. Our NAV Technology serves as a backbone gene therapy research and is widely utilized gene therapy platform across diverse disease applications. We selectively license components of our NAV Technology Platform to third-party companies whose vision and commitment to gene therapy is aligned with our own. Our internal product candidates are being developed across the spectrum of therapeutic areas. In retinal diseases our gene therapy product candidate encodes for our continuous long term expression of an antibody and can potentially help…

Thanks, Ken. First, I'd like to say that I'm thrilled to join the REGENXBIO team. It's a time of exciting momentum for the company as we advance our breakthrough science with curative potential for both rare diseases and diseases that broadly impact public health. As a reminder, our lead product candidates are currently targeting the following indications, wet age-related macular degeneration or wet AMD, mucopolysaccharidosis type I and type II or MPS I and II, homozygous familial hypercholesterolemia or HoFH and late infantile neuronal ceroid lipofuscinosis type II disease or CLN2 disease, a form of Batten disease. I'll begin with our RGX-314 program for the treatment of wet AMD, a disease that affects more than 2 million patients in the U.S., Europe and Japan. Patients with wet AMD usually require anti-VEGF therapy as frequently as every month indefinitely to prevent vision loss. Continuing a long-term therapy with intraocular anti-VEGF injections is a burden to patients and families and many patients struggle to comply with the recommended therapeutic regimen, leading to under treatment and ultimately vision loss over time. RGX-314 utilizes the NAV AAV8 vector, which encompasses a gene that is introduced into retinal cells where it is designed to encode for the long-term continuous expression of a therapeutic anti-VEGF protein. The expressed anti-VEGF antibody fab or antibody fragment potentially halts the proliferation of blood vessels in the retina, the hallmark of wet AMD. The NAV AAV8 vector has been selected for this product candidate, because it has demonstrated effective transduction of retinal cells and the ability to produce and sustain high levels of therapeutic protein over the long term in multiple pre-clinical animal models. Today we reported that Cohort 5 is nearing completion at a dose of 2.5x10^11 genome copies per eye in the Phase 1/2a trial of RGX-314 and…

Thanks, Steve. We are very encouraged by these updates. REGENXBIO has an extensive footprint in the gene therapy space and our leadership and scientific innovation could potentially bring many breakthrough onetime gene therapy treatments to market with our own in-house lead candidates, as well as product candidates developed by our licensee network and enabled by REGENXBIO's NAV Technology. As of March 31, 2019 our technology was being applied in more than 20 partnered product candidates in development by NAV Technology licensees and 14 of these partnered product candidates are in active clinical development, across a broad range of therapeutic areas in disease indications, including 2 clinical trials in hemophilia A, one sponsored by Bayer in partnership with Ultragenyx and one by Takeda. Later this month, we anticipate FDA approval of Novartis' ZOLGENSMA for the treatment of spinal muscular atrophy or SMA Type 1 in the United States. This event will mark the first approval of a product based on NAV Technology. SMA Type 1 is a deadly neuromuscular disease commonly affecting young children. ZOLGENSMA could potentially provide new hope to patients and families suffering from SMA, and we are proud to be a contributor to this milestone through our license agreement with AveXis, now a wholly-owned subsidiary of Novartis. ZOLGENSMA uses the NAV AAV9 vector. REGENXBIO expects to receive total milestone payments in the high single-digit millions upon U.S. and EU approval and is eligible to receive an additional $80 million in potential future commercial milestone payments. In addition, we will expect to receive mid single to low double-digit royalties on worldwide net product sales. Earlier this week at the American Academy of Neurology Meeting in Philadelphia, Novartis presented interim data from their Phase I study of ZOLGENSMA in type II SMA and Phase III study designed to evaluate ZOLGENSMA…

Thank you, Maverick. REGENXBIO ended the quarter on March 31, 2019 with cash, cash equivalents and marketable securities totaling $444.3 million compared to $470.6 million as of December 31st, 2018. The decrease was primarily attributable to net cash flows used in operating activities of $29.3 million. Revenues were $900,000 for the 3 months ended March 31, 2019, compared to $132.4 million for the same period in 2018. The decrease was primarily attributable to $132.1 million of nonrecurring revenue recognized during the 3 months ended March 31 2018 under our amended license agreement with AveXis for the development and commercialization of treatments for SMA research and development expenses were $25.2 million for the 3 months ended March 31 2019, compared to $19.6 million for the same period in 2018. The increase was primarily attributable to personal cost as a result of increased headcount, laboratory and facilities costs and external expenses associated with conducting clinical trials and manufacturing-related services. General and administrative expenses were $11.6 million for the 3 months ended March 31, 2019, compared to $8.4 million for the same periods in 2018. The increase was primarily attributable to personnel cost as a result of increased headcount and professional fees for advisory and other services. Net loss was $32.2 million, or $0.89 basic and diluted net loss per share for the 3 months ended March 31, 2019, compared to net income of $104.2 million or 3.30 and $3.04 diluted net income per share for the same period in 2018. As of March 31. 2019 we had 36.6 million common shares outstanding. Upon regulatory approval and product launch, Novartis's ZOLGENSMA is expected to provide REGENXBIO with its first revenue stream from royalties on commercial product sales adding commercial revenue to its existing base of licensing revenue this year. Based on REGENXBIO's current operating plan and excluding any royalties from ZOLGENSMA, REGENXBIO reiterates that it expects its balance in cash, cash equivalents and marketable securities to be between 330 and $350 million as of December 31st, 2019, which will be used to support the continued development of its lead product candidate programs. With that I will turn the call back to Maverick to provide final thoughts and review our upcoming 2019 milestones.

To summarize what we've discussed today, as Iceman just described, we are expecting seeing the approval of ZOLGENSMA by Novartis, the FDA in the U.S. In addition, focusing on REGENX's internal programs, the interim Cohort 3 data from the Phase I/IIa trial for wet AMD provided evidence that onetime treatment RGX-314 can achieve long-lasting clinical effect reaching over one year with 50% of subjects treated with RGX-314 continuing to remain free of anti-VEGF injections. Our expanded Phase I/IIa trial for RGX-314 is progressing as planned and is expected to complete enrollment in the first half of 2019. We plan to present top line data from that trial by the end of 2019 that will include new data from Cohort 4 and Cohort 5 and we're on track to initiate a Phase IIb trial for wet AMD in late 2019. We announced today that we also plan to file a new IND for RGX-314 in the second half of this year for an additional Phase II clinical trial in diabetic retinopathy, a progressive retinal conditioning and leading cause of blindness and impaired vision in adults between 24 and 74 years of age. Diabetic retinopathy is a serious public health concern. Almost 30 million Americans have diabetes and nearly 8 million of them are estimated to have diabetic retinopathy. Dosing has begun in the first of 2 expected cohorts in the Phase I/II clinical trial for RGX-121 for the treatment of MPS II. We had a 28-week safety assessment where RGX-121 continues to be well tolerated with no SAEs reported and additional recruitment and site activation are ongoing. Recruitment and site activation also continue in the Phase I clinical trial of RGX-111 for the treatment MPS I. For RGX-501 for the treatment of HoFH patient screening is reinitiated for enrollment of subjects in Cohort 2 with corticosteroid prophylaxis. Now we expect to present interim data updates for the RGX-121, 111 and 501 trials, all in the second half of 2019. And lastly for RGX-181 for the treatment of CLN2 disease, the IND enabling studies are progressing and we expect to file an IND or a foreign equivalent for the first in human clinical trial evaluating RGX-111 in the second half 2019. At REGENXBIO we are committed to improving lives through the curative potential of gene therapy based on our proprietary NAV Technology Platform. Looking back at all that we've accomplished over the past 10 years, I'd like to take a moment again to recognize the excellent work by our employees, partners, clinical trial investigators and of course every individual and family who've chosen to participate in our clinical trials. With our innovative science, inspired people, partners, strong cash position, we're well positioned to achieve future milestones as we embark on the next decade in our drive to advance therapies for patients with significant unmet medical needs. And with that we'll end the call and turn it over for questions. Operator?

[Operator Instructions]. Our first question comes from the line of Matthew Harrison from Morgan Stanley. You may begin.

Thanks for taking the question and thanks for all the updates. I guess, first one for me, can you just comment briefly, you called out the protein levels at one year for both -- all the patients and then the patients that didn't have a VEGF injection. I guess the question would be sort of an 80 nanogram per milliliter difference between them or the levels have been trending sort of above 250 for the people that didn't get injections. Do you see that as a threshold effect or how would you interpret the levels in that group versus the levels in the overall group?

Matt, I'll start off and maybe ask Steve if he wants to jump in as well. I think, look we're encouraged that we're seeing consistency across the whole group and as well, consistently across the 3 that haven't received any injections which still for us is the purest form of evaluation based on the assay method that we're using and the potential for interference. Although I think what we're most encouraged by is that we continue to see those related correlations to the BCVA and CRT related to protein expression. And I think where -- the hypothesis of this program from the outset has been that using AAV gene therapy to achieve durable sustained protein levels was going to have the best effect on the disease. We're seeing that at Cohort 3 now at one year. Steve, I don't know if you have anything to add.

Sure. Thanks for the question, Matthew. Yes, I think it's important to remember also take a step back and realize these are aqueous humor concentration. So it's already a proxy for what you're getting produced in the retina. So I don't think it's kind of a thing that you can put a fine point on exactly what threshold is going to be relevant. So really as Ken has mentioned what we look at here is the consistency over time in these patients where whether you look at the 3 subjects or the 6 subjects whichever and you look at, we see sustained protein expression.

Okay, thanks. That's helpful. And then -- and my second question is just on the MPS I and II programs, it sounds like recruitment has been slow in those programs. But you've committed to some sort of update in the second half. Can you just help frame for us what kind of information you think we should reasonably expect in the second half?

Yes, Matt, I mean we obviously checked in on the 121 program in terms of the safety assessment that occurred at 20 weeks and the protocol has us collecting samples throughout the trial, including CSF, serum for additional evaluation of biomarkers and protocol also allows for evaluation of other clinical measures. So I think we've said from the outset when we started off this year we're going to collect as much data as we can based on the pace of enrollment throughout the year. I certainly would expect that we're going to have aspects of a broader safety story as well as the emergence of some of those initial clinical biomarkers and other clinical evaluations by the end of 2019 in both trials.

Our next question comes from the line of Gena Wang from Barclays. You may begin.

Thank you. My first question is regarding wet AMD program. For the Cohort 3, the rescue injection. The injection should be 4.6 based on our calculation. How is that compared to the two cohorts at the lower doses? I think the reason I am asking is, did you see any protein dependent response in terms of the rescue injection?

Yes. So we updated this on corporate deck today Gena and I think we reported that in Cohort 1 patients were receiving on average of over 10 injections for a year and in Cohort 2 close to 9 injections. So there is even a noticeable difference, I think, obviously between Cohort 1 and Cohort 2 and what we're seeing across the whole body of Cohort 3.

Okay, great. And also I think the protein level seems that there is some slight decline compared to the six months? Is there any concern or do you think that that's just within the normal experimental error?

Yes, I think you've hit on it there, Gena. We're seeing things that we think are a function of what we know about this assay method and its overall accuracy and our interpretation. And I think informed by even how sort of FDA guidances would interpret assay results like this is that we're seeing a substantially equivalent results here, based on the ECL assays.

Okay. And regarding diabetic retinopathy, what would be the dose for this indication?

Hi, Gena. Steve here. So that's to be determined. One of the nice things is we have the ongoing wet AMD study and data is still to come from Cohorts 4 and 5 where we're going to learn a lot from those. So both in confirming the safety and tolerability as well as seeing effect. One of the nice things about DR in general, as we know that it is a highly VEGF driven disease, whether at the stage of diabetic retinopathy or the actual complications such as DME and PVR. So we can learn from also the pharmacodynamic response that we see in the ongoing study. So that will inform before finalization of the protocol for the DR Phase I -- the Phase II study.

Okay. Well, will you be thinking one dose or potentially three will be two doses?

I think it's likely we consider two doses, more than one dose. But again -- a final decision is really going to depend on what we see going forward.

Okay, great. And my last question is regarding the IP for AAV9 indication in SMA given the approval will happen anytime soon? So what would be your plan for extension for both Europe and U.S.? And also will this apply to both IV and intracisternal administration?

Right. So the AAV9 IP that was originally licensed to AveXis back in 2014. Covered the use of AAV9 for the treatment of all forms of SMA, including all routes of administration, basically sort of parent patent that focused on gene transfer with AAV9. That was very novel and non-obvious at the time of the discovery. So all of the work that is covered under the ZOLGENSMA program relates to that field that was licensed. And we've also of course when we amended the agreement with AveXis in early 2018, included additional intellectual property that related to the program and future development opportunities that AveXis know Novartis will have. As we've talked about before and I think with you and others, Gena, the plan for how we will work to approach patent term extension in the U.S. and Europe is kind of known processes and we're going to be talking to the sponsor, which is now AveXis subsidiary Novartis about working together to initiate certain applications where needed. In other cases, it's going to be our responsibility as REGENX to affect certain applications that need to go in in different jurisdictions. And as you alluded to the trigger point here is going to be in all cases, the actual licensure of ZOLGENSMA which we're anticipating this month, at least in the U.S.

Our next question comes from the line of Mani Foroohar from SVB Leerink. You may begin.

Hey, guys. I got two quick questions. As I'm looking at the protein levels that just goes in the press release, across Cohort 3 we are looking at a 180 nanograms per ml and we've got 260 per ml in the three anti-VEGF injection free patients. That implies about 100 per ml for the remaining three patients. Have you disclosed or do you plan to disclose the protein level curve for those patients as you have here, one month, six months, one year or do you think that that's not really useful data and it's not really interpretable?

So, we have disclosed one -- well, you mentioned that we've disclosed the 180 at 12 months and six than we had disclosed, the one month and the six-month, Mani. So it's all available at this point.

Okay. Right. That's helpful. And the other question that I have, when you think about moving forward into a pivotal study, the study that you've RGX-314 thus far evolved and demonstrated anti-VEGF responders with multiple years of therapy. Do you expect that it will be -- that a pivotal study head to head versus an approved product would also be exclusively in anti-VEGF responders or will there be some anti-VEGF-naive patients there?

As we look at it now, I think going forward we obviously want patients who are anti-VEGF responders. We will give more details on our forward-looking clinical development plan in the second half of this year.

Our next question comes from the line of Josh Schimmer from Evercore. You may begin.

If I run some really simple back of the envelope math, the cohort of -- the patients in Cohort 3 were not VEGF injection free. And then I adjust the protein expression levels in those patients and think about Cohort 4, I would have expected that all those Cohort 4 patients since their doses is so much higher than Cohort 3 will now be in this 250 type band to be anti-VEGF injection free in the follow-up. And yet you then went to Cohort 5. So is there -- is the math wrong to say that Cohort 4 should have had all patients now with adequate protein levels to avoid further anti-VEGF injections or is that not the case?

Hey, Josh. Thanks a lot. Thoughtful question as usual. I think first -- the primary driver for addressing moving to Cohort 5 was really end of your discussions at 2018 with FDA about wanting to think about how we would broaden and deepen the 314 program including, like the example today moving into diabetic retinopathy. And I think we established that building the most complete safety database from the Phase I now I/II2a study was the best possible platform to do that to provide us multiple absolute flexibility on a going forward basis. And I think the fact that we will not have to run any additional preclinical studies, the fact that we will leverage the safety data and leverage dose selection from the Phase I/IIa moving directly into DR is an example of that. Otherwise, yeah, look in theory, I think we believe that more protein is going to show more response. And I think that's been the case in what we've seen with Cohorts 1,2, 3 and I think it's what we're looking to explore and even by increasing the size of the cohorts with Cohort 4 and Cohort 5. What we also know is that wet AMD in particular is a heterogeneous disease. And we also want to make some assessments of how we will power programs going forward in order to be able to establish best possible outcomes with what we already are seeing as emerging is encouraging data with respect to clinical response to a durable levels of protein. Steve, I don't know if you want to add anything.

No. That works.

Do you envision different doses then for diabetic retinopathy versus wet AMD?

Well, again, we'll have to see what we find here. I think there is comfort in all the data that exists with various anti-VEGF programs where we can look at the pharmacodynamic response of different anti-VEGF programs in both different DR and DME indications and also wet AMD. That gives us some comfort in terms of potential range of doses where we might expect certain PK findings to translate into the intended pharmacodynamic effect in DR. But again, we're going to have to see the results that we get from the wet AMD study.

Maybe last question, is there any clinical features or predictors of which patients may have higher versus lower protein expression levels within each cohort?

Well, I think it's important to note, these are small sample sizes. So there is a limit to how much you can read the tea leaves so to speak in terms of what variables might be related or not related to PK or PD for that matter.

I think we're happy to have this protein data as another place to sort of anchor ourselves into what's happening scientifically as well as clinically and I think we're also encouraged by the fact that we're running this study at multiple sites and sort of as we've talked about in the past wanting to think about all the variables that go into a successful product for a one-time subretinal initiation of treatment. It was about measuring protein, it was about getting early data on sort of different surgical centers and their ability to do this and to scale like we talked about at the investor meeting, and now we're collecting the clinical data as well. So we're excited about where this is at this point, encouraged by what we're seeing. Second half of the year going to be a lot of decisions to be made.

[Operator Instructions]. Our next question comes from the line of Ying Huang from Bank of America Merrill Lynch. You may begin.

Hi, good afternoon. This is Chen on behalf of Ying. Sorry there were some technical difficulties. I have a couple of questions. The first one is like when I was doing the calculation, right, the Cohorts 3, with the rescue you received average of 4.6 injections. But if we do the calculation on the BCVAs, almost like a zero. So I wonder what are you thinking about -- like what criterias are you actually thinking about when doing the rescue. And also want to confirm that the patients Cohorts 3 without the rescue, are they all dry in their eyes?

Well, on the question of rescue. We have actually pretty strict rescue criteria here. So we're not letting patients go. And certainly relative to precedent of other trials that are out there these patients are getting treated if there is a decrease in visual acuity of 5 letters associated with fluid or if there is an increase in fluid or ocular hemorrhage. And that constellation of criteria is actually stricter than some of the other concurrent studies that are out there.

Okay. And a follow-up on the patients without rescue. So if you compare 12 months you have average increase of 10 letters versus 13 in 9 months. I wonder whether that's just like variability or you think that is a trend going down in all the three patients?

Yes, I think especially with BCVA if you're talking about a magnitude of 3 letters or 4 letters, that's certainly within random variation that you would expect in a -- at different time points in a trial.

Okay. And the next one is that, do you think there is a possibility to retreat patient who are not achieving sufficient protein levels at this point? Is there something in the plan?

I think we need to alleviate here for that. Chen that's something that I think all of us in gene therapy are interested in exploring scientifically at different levels, but it is not currently part of any clinical plan or design in terms of advancement of 314 in the near term.

Thank you. And we're showing no further questions at this time. I'd like to turn the call back to Mr. Ken Mills for closing remarks.

Thank you, operator. I just wanted to point out to everyone who are listening on the call that we did provide some updates of the data also in our corporate deck that can be found on the website, including some of the longitudinal data on the subjects from Cohort 3 in more detail. So, thanks everyone for joining us today. We look forward to providing with further updates. We're really encouraged by what we're seeing this past quarter in terms of the success in execution on clinical development, both at REGENEX and through our partners. Have a great night.

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.