Published in Business

Regenex Bio reports Q1 2023 financial results and recent operational highlights

Regenex Bio Inc. announced financial results for the first quarter ended March 31, 2023, and recent operational highlights.

"RegenexBio is well-positioned for a transformative year, with multiple clinical milestones and updates anticipated in 2023. Our goal in partnering our core expertise in gene therapy with AbbVie's leadership in eye care and their global infrastructure was to expand and advance the reach of our retinal programs for patients in need of a potential one-time gene therapy, and we are pleased to progress this program with a vision of benefiting patients worldwide. Based on the encouraging safety and clinical profiles, we believe ABBV-RGX-314 has the potential to be a highly differentiated product for millions of patients." said Kenneth T. Mills, president and CEO of RegenexBio. "We also continue to make tremendous strides in our rare disease pipeline, advancing clinical trials in Duchenne, Hunter and Hurler syndromes and Batten disease, and we anticipate more updates across each of these programs in 2023. Overall, with an active pipeline of clinical-stage products, we are making excellent progress advancing our '5x'25' strategy to bring leading, ground-breaking AAV Therapeutics to patients in need."

AbbVie Eye Care Collaboration Update

RegenexBio announced updates from its eye care collaboration with AbbVie to develop and commercialize a potential one-time gene therapy for the treatment of chronic retinal diseases.

The updates include the transfer of the Investigational New Drug (IND) applications to AbbVie for all ongoing clinical trials and the expansion of the ATMOSPHERE and ASCENT pivotal trials for the treatment of patients with wet age-related macular degeneration (wet AMD) using subretinal delivery to support new global registration plans.

As part of the IND transfers, the investigational gene therapy RGX-314 has been renamed ABBV-RGX-314.

As outlined in the original collaboration agreement, beginning in 2023, AbbVie has been responsible for the majority of all development expenses for ABBV-RGX-314. The transfer of the INDs enables AbbVie to serve as lead regulatory party in the U.S. and globally.

AbbVie will lead the clinical development and commercialization of ABBV-RGX-314 globally. AbbVie and RegenexBio will continue to collaborate on additional trials of ABBV-RGX-314.

ABBV-RGX-314 is currently being evaluated in nine ongoing clinical trials in the U.S. and Canada, including two pivotal trials, a phase 2 bridging study, a long-term follow-up study, and a Fellow Eye treatment study in patients with wet AMD, all utilizing subretinal delivery, as well as two phase 2 clinical trials in patients with wet AMD and diabetic retinopathy (DR), and two corresponding Long-term Follow-up studies, all utilizing in-office suprachoroidal delivery.

The pivotal program utilizing subretinal delivery is now expected to add new sites in Europe, Japan, and Israel to advance global development plans. Additional clinical trial applications will be submitted to the European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency in Japan. The ATMOSPHERE and ASCENT trials are expected to expand enrollment to approximately 540 and 660 patients, respectively.

As prospectively allowed in the pivotal trial protocols, the enrollment expansion is also expected to support the increase in power of primary and secondary endpoints to enable additional global regulatory submissions and labelling options.

The new global site plans and expanded enrollment targets are expected to support regulatory submissions with the U.S. Food and Drug Agency (FDA) and the EMA in late 2025 through the first half of 2026.

Also as previously announced, under the collaboration, RegenexBio will continue to lead the manufacturing of ABBV-RGX-314 for clinical development and U.S. commercial supply, and AbbVie will lead manufacturing of ABBV-RGX-314 for commercial supply outside the U.S.

Additionally, cGMP material produced by RegenexBio's proprietary NAVXpress platform process has been incorporated into the ongoing clinical trials, including the ATMOSPHERE and ASCENT pivotal trials. RegenexBio shall participate in U.S. commercialization efforts as provided under a mutually agreed upon commercialization plan.

RegenexBio and AbbVie will share equally in profits from net sales of ABBV-RGX-314 in the U.S. and AbbVie will pay RegenexBio tiered royalties on net sales outside the U.S.

Program Highlights and Milestones

ABBV-RGX-314: ABBV-RGX-314 is an investigational one-time AAV Therapeutic being developed in collaboration with AbbVie for the treatment of wet AMD, DR and other additional chronic retinal conditions. ABBV-RGX-314 uses the NAV AAV8 vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor (VEGF).

  • ABBV-RGX-314 Subretinal Delivery for the Treatment of Wet AMD
  • Ahead of global expansion, U.S. enrollment is ongoing in ATMOSPHERE and ASCENT. Material from RegenexBio's NAVXpress platform process has been incorporated in the pivotal trials and is expected to be produced at RegenexBio's Manufacturing Innovation Center for future commercialization of RGX-314.
  • RegenexBio also announced that a Fellow Eye Treatment study has also been initiated as part of the pivotal program using subretinal delivery. This study will evaluate the safety, efficacy, and immunogenicity of subretinal ABBV-RGX-314 administration in the fellow eye of patients having bilateral disease from ATMOSPHERE and ASCENT who previously received a subretinal injection of ABBV-RGX-314. Data from patients enrolled in this study are expected to further support global regulatory submission plans.
  • In February 2023, interim data was presented from the Phase II bridging study demonstrating that ABBV-RGX-314 manufactured using RegenexBio's NAVXpress platform process, material from which has been incorporated into the pivotal trials, was well tolerated and exhibited a similar clinical profile to the initial adherent cell culture process used in the Phase I/IIa trial. Patients in the two high dose cohorts also demonstrated stable to improved BCVA and CRT, and meaningful reductions in anti-VEGF burden, with a majority of subjects injection-free. The Phase II pharmacodynamic study is designed to evaluate the same dose levels being used in the two pivotal trials.
  • ABBV-RGX-314 Suprachoroidal Delivery for the Treatment of Wet AMD
  • RegenexBio has completed enrollment of Cohort 6 in the phase 2 AAVIATE trial. Cohort 6 (dose level 3) incorporated short-course prophylactic ocular steroids following ABBV-RGX-314 administration to evaluate the ability to prevent or reduce the occurrence of the mild to moderate intraocular inflammation seen in previous cohorts. Patients were enrolled in Cohort 6 regardless of neutralizing antibody (NAb) status.
  • RegenexBio expects to report additional interim trial data from the phase 2 AAVIATE trial, including initial data from Cohort 6, in the second half of 2023.
  • ABBV-RGX-314 Suprachoroidal Delivery for the Treatment of DR
  • RegenexBio has completed enrollment in Cohorts 4 and 5 (dose level 3) in the phase 2 ALTITUDE trial. In these cohorts, patients were stratified by Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (DRSS) levels and all received short-course prophylactic ocular steroids following ABBV-RGX-314 administration.
  • RegenexBio expects to report additional interim trial data, including initial data from the third dose level, in the second half of 2023.

RGX-202: RGX-202 is an investigational one-time AAV Therapeutic for the treatment of Duchenne Muscular Dystrophy (Duchenne), using the NAV AAV8 vector to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain as well as a muscle specific promoter to support a targeted therapy for improved resistance to muscle damage associated with Duchenne.

  • The phase 1/2 AFFINITY DUCHENNE trial continues to recruit patients and is expected to use commercial-scale cGMP material from the RegenexBio Manufacturing Innovation Center in the clinical trial.
  • In April, RegenexBio announced the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to RGX-202 for the treatment of Duchenne. Fast Track designation aims to facilitate the development and expedite the review of new therapeutics to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.
  • RegenexBio is also recruiting patients in the AFFINITY BEYOND trial, an observational screening study to evaluate the prevalence of AAV8 antibodies in patients with Duchenne up to 12 years of age. Information collected in this study may be used to identify potential participants for the AFFINITY DUCHENNE trial and potential future trials of RGX-202.
  • RegenexBio continues to expect to report initial data from the Phase I/II AFFINITY DUCHENNE trial in the second half of 2023.

RGX-121: RGX-121 is an investigational one-time AAV Therapeutic for the treatment of Mucopolysaccharidosis Type II (MPS II), also known as Hunter Syndrome, using the NAV AAV9 vector to deliver the gene that encodes the iduronate-2-sulfatase (I2S) enzyme.

  • The Phase I/II/III CAMPSIITE trial of MPS II patients aged 4 months up to 5 years is ongoing and is expected to incorporate material from the NAVXpress platform process manufactured at the RegenexBioManufacturing Innovation Center to support the future commercialization of RGX-121.
  • In February 2023, REGENXBIO announced additional interim data from the Phase I/II part of the CAMPSIITE trial, demonstrating that RGX-121 continued to be well-tolerated across 15 patients. Patients receiving the pivotal program dose level continued to demonstrate the largest reductions in CSF GAGs, including Heparin Sulfate (HS) and HS D2S6, which approached normal levels at 48 weeks. CSF GAGs have the potential to be considered a surrogate biomarker that is reasonably likely to predict clinical benefit in MPS II disease under the accelerated approval pathway, as buildup of GAGs in the CSF of MPS II patients correlates with clinical manifestations, including neurodevelopmental deficits. In addition, improvements in neurodevelopmental and daily activity skill acquisition were observed up to three years after RGX-121 administration.
  • A Phase I/II trial of RGX-121 for the treatment of pediatric patients with MPS II over the age of five years old is also ongoing.
  • CAMPSIITE is expected to complete enrollment of 10 MPS II patients in the first half of 2023 to support a BLA filing in 2024 using the accelerated approval pathway.

RGX-111: RGX-111 is an investigational one-time AAV Therapeutic for the treatment of severe Mucopolysaccharidosis Type I (MPS I), using the NAV AAV9 vector to deliver the α-l-iduronidase (IDUA) gene.

  • A phase 1/2 trial of RGX-111 for the treatment of MPS I is fully enrolled with follow-up ongoing.
  • RegenexBio has recently completed the manufacture of commercial-scale cGMP material using the NAVXpress platform process at the RegenexBio Manufacturing Innovation Center to support the continued development of RGX-111.
  • In February 2023, RegenexBio announced additional positive interim data from the phase 1/2 trial demonstrating that RGX-111 was well tolerated in eight patients. Biomarker and neurodevelopmental assessments indicated an encouraging CNS profile in patients dosed with RGX-111.
  • RegenexBio expects to complete analytical characterization of the commercial-scale cGMP material and share additional updates on program plans in the second half of 2023.

RGX-181: RGX-181 is an investigational one-time AAV Therapeutic for the treatment of late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a form of Batten disease, using the NAV AAV9 vector to deliver the TPP1 gene directly to the central nervous system.

  • Physician investigators in Brazil continue with follow up for the first child with CLN2 disease dosed with RGX-181 under a single-patient investigator-initiated study.
  • REGENXBIO plans to provide a program update by the end of 2023.

RGX-381: RGX-381 is an investigational one-time AAV Therapeutic for the treatment of the ocular manifestations of CLN2 disease using the NAV AAV9 vector to deliver the TPP1 gene directly to the retina.

  • The phase 1/2 first-in-human, open-label, dose-escalation clinical trial of RGX-381 is on track to initiate in the second quarter of 2023. The trial will evaluate the safety and tolerability, as well as the effect on retinal anatomic and functional outcomes, of the subretinal delivery of RGX-381 for the treatment of ocular manifestations of CLN2 disease.

Operational Updates

  • The RegenexBio Manufacturing Innovation Center in Maryland is fully operational, producing GMP bulk substance lots to support programs using the NAVXpress platform process. RegenexBiois one of only a few gene therapy companies worldwide with a GMP facility capable of production at scales up to 2,000 liters.
  • In 2023, RegenexBio continues to utilize the facility to produce commercial-scale cGMP material for its entire clinical pipeline and performance qualification lots to support planned regulatory filings for ABBV-RGX-314 and RGX-121.

NAV Technology Licensee Program Highlights

As of March 31, 2023, RegenexBio's NAV Technology Platform was being applied in one marketed product and multiple clinical stage partnered programs, with the potential to impact a broad range of therapeutic areas and disease indications.

  • Zolgensma, a one-time AAV Therapeutic for the treatment of spinal muscular atrophy (SMA), is a marketed product utilizing REGENXBIO's NAV AAV9 vector. In April 2023, Novartis AG reported first quarter 2023 global sales of Zolgensma of $309 million.
  • In February 2023, Rocket Pharmaceuticals (Rocket) announced that the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to RP-A501, for the treatment of Danon Disease, that will provide the benefits of added intensive FDA guidance and expedited review through the program's development. The initiation of a Phase II pivotal trial is on track for the second quarter of 2023. As previously disclosed, Rocket anticipates pursuing a single arm, open-label trial with a biomarker-based composite endpoint and a natural history comparator. RP-A501 is being developed as a one-time gene therapy utilizing RegenexBio's NAV AAV9 vector.
  • In February 2023, Ultragenyx Pharmaceutical Inc. (Ultragenyx) announced that in the phase 3 study of DTX401 for Glycogen Storage Disease Type Ia (GSDIa), the last patient has entered the baseline screening period and data readout is expected in the first half of 2024. Ultragenyx also randomized and dosed the first patient in the phase 3 study of DTX301 for Ornithine Transcarbamylase (OTC) Deficiency. DTX401 and DTX301 are both being developed as one-time gene therapies utilizing RegenexBio's NAV AAV8 vector.
  • In February 2023, uniQure N.V. announced it expects to submit an investigational new drug application and initiate a phase 1/2clinical study of AMT-260 to treat temporal lobe epilepsy in the second half of 2023. AMT-260 is being developed as a one-time gene therapy utilizing RegenexBio's NAV AAV9 vector.