RGX-314 programs for treatment of wet AMD and diabetic retinopathy continue to advance

Plans to initiate a pivotal program of subretinal delivery for wet AMD in 2H 2020, following the 12-month assessment of Cohort 5 patients in the Phase I/IIa trial

FDA removes partial clinical hold on Phase I/IIa trial of subretinal delivery for wet AMD

Phase II trials of suprachoroidal delivery for treatment of wet AMD and diabetic retinopathy expected to begin in 2020

Enrollment continues in Cohort 2 of RGX-121 Phase I/II trial in MPS II, with additional interim data expected in 2020

Interim update from RGX-501 Phase I/II trial in HoFH supports Cohort 2 safety with steroid prophylaxis; LDL-C measures expected in 1H 2020

Utilization of new corporate, research and manufacturing headquarters expected to begin in late 2020, and cGMP manufacturing facility with capacity to produce NAV vectors at scales up to 2,000 liters expected to be fully operational in 2021

Ended 2019 above guidance estimate with $400 million in cash, cash equivalents and marketable securities

RGX-314 for the Treatment of Wet AMD

REGENXBIO expects to initiate a pivotal program for the subretinal delivery of RGX-314 for the treatment of wet AMD in the second half of 2020.

A pivotal clinical trial is expected to investigate the one-time administration of RGX-314 at a single dose compared to anti-VEGF injections, which is the current standard of care for patients with wet AMD. The primary efficacy endpoint in the trial will be the mean change in visual acuity from baseline assessed at 12 months after treatment with RGX-314.

REGENXBIO plans to finalize the design of the trial based on the 12-month assessment of patients in Cohort 5 in the Phase I/IIa trial. This will allow for further characterization of RGX-314-treated patients, enhancements of the trial design and the potential acceleration of the clinical program.

REGENXBIO intends to submit the design of the trial to the FDA in mid-2020 and begin dosing patients in the second half of 2020.

The U.S. Food and Drug Administration (FDA) has removed the partial clinical hold on the Investigational New Drug (IND) application for the Phase I/IIa trial of the subretinal delivery of RGX-314 without modification to the surgical delivery system, after reviewing information provided by the Company. The partial clinical hold was not related to the gene therapy candidate.

As of December 31, 2019, RGX-314 continued to be well-tolerated across all cohorts in the Phase I/IIa trial, with no drug-related serious adverse events (SAEs) reported. All patients in Cohort 5 (2.5 x 1011 GC/eye) have now completed their 6-month follow-up.¹

Patients in Cohort 5 continue to demonstrate a meaningful reduction in anti-vascular endothelial growth factor (anti-VEGF) treatment burden at 6 months following administration of RGX-314, with 8 out of 11 (73%) patients remaining anti-VEGF injection-free, and a reduction across the cohort of over 80% from the mean annualized injection rate during the 12 months prior to administration of RGX-314. Importantly, the Cohort 5 patients continued to demonstrate a mean improvement in vision of +3 ETDRS letters and mean improvement in retinal thickness of -83 microns, while the 8 patients who were anti-VEGF injection-free after administration of RGX-314 showed a mean improvement in vision of +5 ETDRS letters and mean improvement in retinal thickness of -83 microns.

REGENXBIO plans to initiate the Phase II trial of the suprachoroidal delivery of RGX-314 using the SCS Microinjector^TM for the treatment of wet AMD in the first half of 2020.

The trial will build upon data from the Phase I/IIa trial of RGX-314 and is expected to evaluate patients in two dose cohorts of RGX-314 versus a control arm. Interim data is expected from Cohort 1 by the end of 2020.

RGX-314 for the Treatment of Diabetic Retinopathy (DR)

REGENXBIO expects to submit an IND in the first half of 2020 and plans to initiate a Phase II trial of the suprachoroidal delivery of RGX-314 using the SCS Microinjector for the treatment of DR in the second half of 2020.

The trial is expected to evaluate patients in up to three dose cohorts of RGX-314 versus a control arm. Enrollment of Cohort 1 is expected to be complete by the end of 2020, with interim data expected in 2021.

Research Program for the Treatment of Hereditary Angioedema (HAE)

As first announced in July 2019, REGENXBIO is developing a one-time gene therapy candidate to deliver a gene encoding a therapeutic antibody against plasma kallikrein, a key protein of the plasma contact pathway which is left unregulated in patients with HAE.

Preclinical animal studies conducted using NAV AAV8 indicate the potential for a sustained and safe delivery of biologically active antibody at therapeutic concentrations. REGENXBIO expects to select a lead product candidate in the first half of 2020 and provide a program update in the second half of 2020.

Research Program for the Treatment of Neurodegenerative Diseases

REGENXBIO has expanded its exclusive collaboration program with Neurimmune AG to include therapies targeting alpha synuclein, in addition to tauopathies. The program uses Neurimmune’s Reverse Translational Medicine^™ platform along with REGENXBIO’s NAV Technology Platform to design and develop vectorized antibody therapies for neurodegenerative diseases. REGENXBIO expects to provide a program update in the second half of 2020.

RGX-121 for the Treatment of Mucopolysaccharidosis Type II (MPS II)

As previously reported, as of December 16, 2019, RGX-121 was well-tolerated in Cohort 1 of the Phase I/II trial of RGX-121 delivered directly to the central nervous system (CNS), and no drug-related SAEs were reported. Patients in Cohort 1 demonstrated consistent and sustained reduction in heparan sulfate (HS) in the cerebral spinal fluid (CSF) and early signs of neurocognitive stability. HS is a key biomarker of iduronate-2-sulfatase enzyme activity and high amounts of HS accumulate in the CNS of MPS II patients, which closely correlates with neurocognitive decline. Additional data from Cohort 1 are expected to be presented at an upcoming medical conference in early 2020.

Dosing in Cohort 2 has begun, at an increased dose level. REGENXBIO expects to complete enrollment of Cohort 2 in the first half of 2020 and provide interim data in mid-2020.

REGENXBIO expects to provide additional details for a potentially accelerated program pathway following evaluation of interim data from Cohort 2 in the second half of 2020 and subsequent interactions with the FDA, in accordance with the Fast Track designation granted to RGX-121 in 2018.

RGX-501 for the Treatment of Homozygous Familial Hypercholesterolemia (HoFH)

REGENXBIO previously announced the completed dosing of an expanded Cohort 2 in the Phase I/II trial of RGX-501 at a dose of 7.5x10¹² GC/kg and including steroid prophylaxis. Per protocol, patients received at least a 13-week steroid treatment.

As of December 31, 2019, the three patients in the expanded Cohort 2 have been followed for an average of 17 weeks following administration of RGX-501, all beyond the 3-6 week window during which previous transaminase elevations have occurred at this dose level. No SAEs or significant elevations in liver enzyme levels were reported in the expanded Cohort 2 and all patients have completed their steroid treatment or initiated the taper from steroid treatment.

REGENXBIO plans to assess low-density lipoprotein (LDL-C) levels in the expanded Cohort 2 after all patients have completed their steroid treatment, and expects to provide interim data in the first half of 2020.

RGX-111 for the Treatment of Mucopolysaccharidosis Type I (MPS I)

Recruitment, screening and additional site activations are ongoing in the Phase I clinical trial evaluating RGX-111 for the treatment of MPS I. In November 2019, REGENXBIO announced that RGX-111 was administered to a patient with MPS I through an investigator-initiated study. REGENXBIO expects to provide a program update in the second half of 2020.

RGX-181 for the Treatment of Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Disease

REGENXBIO is conducting ongoing preclinical development of RGX-181, including assessment of unmet clinical needs such as neurologic and ophthalmologic manifestations of the disease. REGENXBIO expects to provide a program update in mid-2020 and submit an IND for a first-in-human trial in the second half of 2020.

RGX-314 for the Treatment of Wet AMD

Subretinal delivery

Complete 12-month assessments of Cohort 5 in the Phase I/IIa trial in the first half of 2020.

Initiate a pivotal trial in the second half of 2020.

Suprachoroidal delivery

Initiate Phase II trial in the first half of 2020.

Report interim data from Cohort 1 of the Phase II trial in the second half of 2020.

RGX-314 for the Treatment of DR

Submit IND for a Phase II trial of suprachoroidal delivery in the first half of 2020.

Initiate Phase II trial of suprachoroidal delivery in the second half of 2020.

Research Program for Treatment of HAE

Select lead product candidate in first half of 2020.

Provide program update in the second half of 2020.

Research Program for Treatment of Neurodegenerative Diseases

Provide program update in the second half of 2020.

RGX-121 for the Treatment of MPS II

Present additional interim data from Cohort 1 of the Phase I/II trial in the early 2020.

Provide interim data from Cohort 2 of the Phase I/II trial in mid-2020.

Provide program update in the second half of 2020.

RGX-501 for the Treatment of Homozygous Familial Hypercholesterolemia (HoFH)

Present data from secondary endpoints of the expanded Cohort 2 of the Phase I/II trial, including changes in LDL-C, in the first half of 2020.

Provide program update in the first half of 2020.

RGX-111 for the Treatment of MPS I

Provide program update in the second half of 2020.

RGX-181 for the Treatment of CLN2 Disease

Provide program update in mid-2020.

Submit IND for a first-in-human trial in the second half of 2020.

Current Good Manufacturing Practice (cGMP) Manufacturing Facility

Construction of a new corporate, research and manufacturing headquarters in Rockville, Maryland, continues, with plans to begin utilizing the new headquarters in late 2020.

The new cGMP production facility is expected to allow for production of NAV vectors at scales up to 2,000 liters using REGENXBIO’s platform suspension cell culture process, which will complement REGENXBIO’s current external manufacturing network and capabilities. The cGMP facility is expected to be fully operational starting in 2021.

Novartis AG’s Zolgensma for the Treatment of Spinal Muscular Atrophy (SMA)

REGENXBIO receives tiered royalties on the worldwide sales of Zolgensma up to a low double-digit percentage and is eligible to receive an additional $80 million milestone payment upon the achievement of $1 billion in cumulative net sales. As of October 22, 2019, Novartis reported U.S. Zolgensma sales revenue of $175 million through the third quarter of 2019.

Novartis announced in October 2019 that Zolgensma is currently under regulatory review in Europe with an anticipated regulatory decision in the first quarter of 2020 and in Japan with an anticipated regulatory decision in the first half 2020.

Audentes Therapeutics, Inc.’s AT132 for the Treatment of X-Linked Myotubular Myopathy (XLMTM)

In November 2019, Audentes stated that the Biologics License Application submission for AT132 is planned for mid-2020, and the Marketing Authorization Application submission is planned for the second half of 2020. AT132 uses the NAV AAV8 vector.

One patient died 4.5 months after the administration of RGX-314 as a result of the subject’s underlying disease, which was assessed to be unrelated to RGX-314. At the time of the death, the subject was free of anti-VEGF injections.