RGX-202 Therapeutic Approach - RGX-202 is designed to improve function and preserve muscle health, delivered by proprietary NAV® AAV8 vector[24] - The trial is designed to demonstrate meaningful change in disease trajectory in pursuit of broad label, with positive interim efficacy and safety outcomes reported in Phase I/II[25] - RGX-202 has product purity levels of more than 80% full capsids due to industry-leading manufacturing[21] - A proactive, short-course immune modulation regimen is designed to counter safety concerns common with high-dose AAV gene therapy and to improve safety outcomes[22] AFFINITY DUCHENNE Phase I/II Trial Results - RGX-202 was well-tolerated in 13 patients across both dose levels with no SAEs or AESIs[62] - Biomarker data support consistent robust expression, transduction, and sarcolemmal localization of RGX-202 microdystrophin[62] - At 9 months, Dose Level 2 participants (n=5) demonstrated a mean change in NSAA of 4.8 compared to natural history external controls (n=65)[44] - At 12 months, Dose Level 2 participants (n=4) demonstrated a mean change in NSAA of 6.8 compared to natural history external controls (n=26)[47] - Dose Level 2 timed task velocity changes exceeded MCID benchmarks at 12 months[50] - Caregivers reported improved function in the home and community as measured by key dimensions of the PODCI at 12 months compared to expected decline in natural history[54] Future Development - The company plans for a mid-2026 BLA submission using accelerated approval pathway and a potential FDA approval in 1H 2027[18]

Core Insights - REGENXBIO Inc. announced positive interim data from the Phase I/II AFFINITY DUCHENNE trial for RGX-202, a gene therapy for Duchenne muscular dystrophy, showing consistent functional benefits and safety [1][2][3] Functional Data - RGX-202 participants at dose level 2 (2x10^14 GC/kg) showed significant functional improvements at both 9 and 12 months, exceeding natural history controls on key measures such as the North Star Ambulatory Assessment (NSAA) [4][5] - At 9 months, participants improved an average of 4 points from baseline on NSAA, and at 12 months, the improvement was 4.5 points from baseline, with a 6.8-point increase compared to natural history [5][6] Biomarker Data - Biomarker data indicated robust microdystrophin expression, with one participant aged 2 showing an expression level of 118.6% compared to control [8][10] - The primary endpoint for the pivotal phase is the proportion of participants with microdystrophin expression ≥10% at Week 12 [8] Safety and Tolerability - RGX-202 demonstrated a favorable safety profile with no serious adverse events reported, and common drug-related adverse events included nausea, vomiting, and fatigue [11][12] - The proactive immune modulation regimen and high product purity levels contributed to the positive safety outcomes [11] Pivotal Trial and Future Plans - REGENXBIO is enrolling participants for the pivotal portion of the AFFINITY DUCHENNE trial, aiming to support a Biologics License Application (BLA) submission under accelerated approval by mid-2026 [14][15] - The company plans to share top-line data in the first half of 2026, including biomarker, functional, and safety data [15] About RGX-202 - RGX-202 is designed to improve function and outcomes in Duchenne muscular dystrophy, utilizing a differentiated microdystrophin construct that encodes key regions of dystrophin [17][18] - The therapy aims to support targeted expression of microdystrophin throughout skeletal and heart muscle using the NAV® AAV8 vector [18] About Duchenne Muscular Dystrophy - Duchenne muscular dystrophy is a severe, progressive muscle disease affecting 1 in 3,500 to 5,000 boys born each year, caused by mutations in the dystrophin gene [19] About REGENXBIO Inc. - REGENXBIO is a biotechnology company focused on gene therapy, with a late-stage pipeline including RGX-202 for Duchenne and other investigational therapies for rare diseases [20]

Group 1 - REGENXBIO Inc. will host a webcast to discuss interim functional data from the Phase I/II AFFINITY DUCHENNE® trial of RGX-202, a gene therapy for Duchenne muscular dystrophy [1] - The webcast will feature principal investigator Aravindhan Veerapandiyan, M.D., from Arkansas Children's Hospital [1] - The event is scheduled for June 5, 2025, at 8:00 a.m. EDT, and will be accessible via REGENXBIO's website [2] Group 2 - REGENXBIO is a biotechnology company focused on gene therapy, founded in 2009, and has pioneered AAV gene therapy [3] - The company is advancing a late-stage pipeline of one-time treatments for rare and retinal diseases, including RGX-202 for Duchenne muscular dystrophy [3] - REGENXBIO's investigational therapies have the potential to significantly impact healthcare delivery for millions [3]

Summary of REGENXBIO Conference Call Company Overview - **Company**: REGENXBIO (RGNX) - **Industry**: Biotechnology, specifically focusing on gene therapy Key Points and Arguments Recent Financing Deal - REGENXBIO announced an opportunistic non-dilutive financing deal aimed at pulling forward midterm royalty streams to prepare for pre-commercial launches, including RGX-202 and RGX-314 [2][3] - The financing is characterized as "good debt" since it does not obligate the company to repay if product sales underperform, while retaining the royalty stream if the products become blockbusters [3][4] FDA Interactions and Regulatory Environment - The company is closely monitoring FDA developments, particularly with the nomination of Dr. Prasad, who has been critical of surrogate endpoints [6][7] - REGENXBIO is currently undergoing a review for its Hunter program, with ongoing interactions with the FDA that have been described as routine [7][8] - The company is optimistic about the potential for accelerated approval based on consistent microdystrophin levels associated with functional benefits [8][9] Market Reactions and Competitive Landscape - Following tragic events related to Sarepta's product, there is increased caution among doctors regarding prescribing to non-ambulatory patients, but REGENXBIO has not seen a change in patient enrollment [10][13] - The company views the lowered financial guidance from Sarepta as a potential opportunity, suggesting that a larger prevalence pool may be available by the time REGENXBIO launches its products [15][16] Product Development and Clinical Trials - REGENXBIO is preparing for pivotal studies and expects to report top-line data from these studies in the first half of next year [28][29] - The company is focused on expanding its dataset for the Hunter program and will provide updates on pivotal study enrollment later this year [27][28] Gene Therapy Strategy and Differentiation - REGENXBIO emphasizes its in-house manufacturing capabilities, which allow for the production of 2,500 doses per year at a competitive cost, as a key differentiator in the gene therapy space [49][50] - The company is advancing its subretinal program for wet AMD in collaboration with AbbVie, with pivotal studies enrolling 1,200 patients [37][38] Safety and Efficacy Considerations - The company has implemented a robust immune-modulating regimen to mitigate risks associated with liver-related adverse events, which has been well-received by investigators [12][13] - REGENXBIO is optimistic about the safety profile of its therapies, particularly in the context of the competitive landscape where safety is a critical concern [46][47] Underappreciated Aspects - The company believes that its cash runway has been improved through recent financing and that its in-house manufacturing capabilities are underappreciated aspects of its business model [49][50] Additional Important Content - The company is preparing for potential advisory committee meetings with the FDA but remains optimistic about the likelihood of not needing one based on precedents [29][30] - The potential for a Priority Review Voucher (PRV) upon approval is highlighted, with recent market data indicating values exceeding $150 million [31][32] This summary encapsulates the key discussions and insights from the REGENXBIO conference call, providing a comprehensive overview of the company's current status, strategic direction, and market positioning.

Core Viewpoint - REGENXBIO Inc. has secured a non-dilutive, limited recourse royalty bond agreement of up to $250 million with Healthcare Royalty, which will enhance its cash runway and support upcoming milestones in its gene therapy pipeline [1][2][3] Financing Details - The agreement allows REGENXBIO to receive $150 million at closing, with an extension of cash runway into early 2027 [1][8] - An additional $50 million will be funded upon achieving sales milestones for ZOLGENSMA, and another $50 million will be available upon mutual agreement between the parties [5][6] Strategic Implications - This financing is aimed at advancing late-stage activities, including potential FDA approvals and data readouts for key products such as RGX-121 and RGX-202 [2][3] - The capital infusion is expected to accelerate commercial preparations and maintain REGENXBIO's leadership in rare and retinal gene therapies [2][8] Agreement Terms - HCRx will receive rights to anticipated royalty payments from ZOLGENSMA and other products, with quarterly interest payments based on royalty and milestone revenue [3][4] - The agreement does not include other potential non-dilutive funding sources, such as the sale of a Priority Review Voucher for RGX-121 [6][8] Company Background - REGENXBIO is focused on gene therapy, with a late-stage pipeline targeting rare and retinal diseases, including partnerships with Nippon Shinyaku and AbbVie [8][9] - The company has pioneered AAV gene therapy and aims to improve healthcare delivery through its investigational therapies [9]

Core Insights - The U.S. FDA has accepted the Biologics License Application (BLA) for RGX-121, a gene therapy for Mucopolysaccharidosis II (MPS II), with a target action date of November 9, 2025 [1][5] - NS Pharma will exclusively commercialize RGX-121 in the U.S. upon potential approval, following a strategic partnership with REGENXBIO [2][3] Company Overview - NS Pharma, a subsidiary of Nippon Shinyaku Co., Ltd., focuses on developing and commercializing innovative therapies [8] - REGENXBIO is a clinical-stage biotechnology company specializing in gene therapy, particularly AAV Therapeutics [7] Product Details - RGX-121 is designed to deliver the iduronate-2-sulfatase (IDS) gene to the central nervous system, potentially providing a long-term solution for MPS II [4] - The therapy has received multiple FDA designations, including Orphan Drug Product and Rare Pediatric Disease [5] Disease Context - MPS II, also known as Hunter Syndrome, is a rare genetic disorder caused by a deficiency in the I2S enzyme, leading to significant health challenges, particularly neurological [6]

Core Viewpoint - REGENXBIO Inc. announced that the FDA has accepted the Biologics License Application (BLA) for RGX-121, a potential one-time gene therapy for Mucopolysaccharidosis II (MPS II), with a target action date of November 9, 2025 [1][7]. Company Overview - REGENXBIO is a biotechnology company focused on gene therapy, founded in 2009, and has developed a late-stage pipeline for rare and retinal diseases [6]. - The company has pioneered AAV gene therapy and aims to improve lives through its curative potential [6]. Product Details - RGX-121 (clemidsogene lanparvovec) is designed to deliver the iduronate-2-sulfatase (IDS) gene to the central nervous system, potentially providing a permanent source of the I2S protein [4]. - The therapy aims to address both neurodevelopmental and systemic effects of Hunter syndrome, which currently relies on weekly enzyme replacement therapy [2]. Regulatory Designations - RGX-121 has received multiple designations from the FDA, including Orphan Drug Product, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy (RMAT) [2]. Commercialization Strategy - Following potential FDA approval, RGX-121 will be commercialized by NS Pharma, a subsidiary of Nippon Shinyaku, while REGENXBIO retains all rights and proceeds related to the potential sale of a Priority Review Voucher (PRV) [3].

Group 1 - Regenxbio reported quarterly earnings of $0.12 per share, missing the Zacks Consensus Estimate of $0.41 per share, compared to a loss of $1.38 per share a year ago, representing an earnings surprise of -70.73% [1] - The company posted revenues of $89.01 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 19.07%, compared to year-ago revenues of $15.62 million [2] - Over the last four quarters, Regenxbio has surpassed consensus EPS estimates two times and topped consensus revenue estimates two times [2] Group 2 - The stock's immediate price movement will depend on management's commentary on the earnings call and the sustainability of earnings expectations [3][4] - Regenxbio shares have lost about 2.7% since the beginning of the year, while the S&P 500 has declined by 3.8% [3] - The current consensus EPS estimate for the coming quarter is -$1.21 on $21.98 million in revenues, and -$0.88 on $295.17 million in revenues for the current fiscal year [7] Group 3 - The Medical - Biomedical and Genetics industry, to which Regenxbio belongs, is currently in the top 34% of the Zacks industries, indicating a favorable outlook [8] - Empirical research shows a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can be tracked by investors [5][6]

Financial Data and Key Metrics Changes - REGENXBIO ended the quarter on March 31, 2025, with cash, cash equivalents, and marketable securities of $272 million, an increase from $245 million as of December 31, 2024, primarily driven by a $110 million upfront payment from the Nippon Shinyaku collaboration [24] - R&D expenses were $53 million for the quarter ended March 31, 2025, compared to $54.8 million for the same quarter in 2024, reflecting a decrease due to clinical trial expenses for RGX-314 and RGX-202 [25] Business Line Data and Key Metrics Changes - RGX-121, a potential first gene therapy for MPS II, is on track for potential FDA approval in the second half of 2025, with a BLA submitted under the accelerated approval pathway [8][9] - RGX-202, a next-generation candidate for Duchenne muscular dystrophy (DMD), has surpassed 50% enrollment in its pivotal study and is expected to submit a BLA in mid-2026 [10][11] - The retinal program, RGX-314, is advancing in two pivotal studies for wet AMD and is on track to be the first gene therapy on the market for this condition [12][19] Market Data and Key Metrics Changes - The DMD market is projected to have over half of the prevalent population untreated by 2027, highlighting a significant opportunity for RGX-202 [11] - The wet AMD and diabetic retinopathy markets represent large multibillion-dollar commercial opportunities, with RGX-314 positioned to serve as a meaningful alternative to current treatments [12][19] Company Strategy and Development Direction - The company is focused on transitioning to a commercial stage with in-house manufacturing capabilities and plans to secure non-dilutive funding [6][8] - A strategic partnership with Nippon Shinyaku aims to commercialize the neurodegenerative franchise, including RGX-121 and RGX-111 [9] - The company is preparing for commercial supply manufacturing of RGX-202 in anticipation of a 2027 launch [11][27] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the imminent acceptance of the BLA for RGX-121 and the positive trajectory of clinical programs [34][51] - The company is optimistic about the evolving regulatory landscape and the potential for accelerated approval pathways, particularly in light of recent developments in the industry [36][44] Other Important Information - The company has a robust cash runway expected to fund operations into the second half of 2026, with potential extensions through non-dilutive financing options [25][26] - The manufacturing innovation center in Rockville, Maryland, is capable of producing up to 2,500 doses of RGX-202 annually, ensuring readiness for market needs [11][12] Q&A Session Summary Question: Timing for the Hunter BLA - Management indicated that the BLA acceptance is imminent and they feel confident about the review process [34] Question: Competitor Insights and Regulatory Expectations - Management discussed the evolving expectations for accelerated approval in DMD, emphasizing the strength of their safety and functional data [36][44] Question: Changes in FDA Requirements - Management noted that there are no anticipated changes in the accelerated approval pathway and enrollment is on track [43][44] Question: Planning for Diabetic Retinopathy Phase III Trial - Management confirmed ongoing interactions with the FDA and that they are on track for first patient dosing this year [55] Question: Updates on DMD Functional Data - Management plans to release additional functional data in the first half of the year, focusing on dose level two patients [62][88] Question: Impact of Recent Pricing Announcements - Management stated it is too early to assess the impact of recent pricing discussions on their gene therapies [104]

Financial Data and Key Metrics Changes - REGENXBIO ended the quarter on March 31, 2025, with cash, cash equivalents, and marketable securities of $272 million, an increase from $245 million as of December 31, 2024, primarily driven by a $110 million upfront payment from the Nippon Shinyaku collaboration [19][20]. - R&D expenses for the quarter were $53 million, down from $54.8 million in the same quarter of 2024, mainly due to clinical trial expenses for RGX-314 and RGX-202 [20]. Business Line Data and Key Metrics Changes - RGX-121, a gene therapy for MPS II, is on track for potential FDA approval in the second half of 2025, with a BLA submitted under the accelerated approval pathway [5][6]. - RGX-202, a candidate for Duchenne muscular dystrophy (DMD), has surpassed 50% enrollment in its pivotal study and is expected to submit a BLA in mid-2026 [7][12]. - The retinal program, RGX-314, is advancing in two pivotal studies for wet AMD and is on track to be the first gene therapy for this condition [9][16]. Market Data and Key Metrics Changes - The DMD market is projected to have over half of the prevalent population untreated by 2027, highlighting a significant opportunity for RGX-202 [8]. - The wet AMD and diabetic retinopathy markets represent large multibillion-dollar commercial opportunities, with RGX-314 positioned to serve as a meaningful alternative to current treatments [9][16]. Company Strategy and Development Direction - The company is focused on transitioning to a commercial stage with in-house manufacturing capabilities and plans to secure non-dilutive funding [4][5]. - A strategic partnership with Nippon Shinyaku aims to commercialize the neurodegenerative franchise, including RGX-121 and RGX-111 [6]. - The company is preparing for commercial supply manufacturing of RGX-202 in anticipation of a 2027 launch [8][24]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the clinical progress and the potential for multiple first or best-in-class gene therapies to reach patients in the coming years [4][10]. - The company is optimistic about the FDA's review process for RGX-121 and believes the data supports a favorable benefit-risk profile for its gene therapies [30][46]. Other Important Information - The company has a robust cash runway expected to fund operations into the second half of 2026, with potential extensions through non-dilutive financing options [20][21]. - The manufacturing innovation center in Rockville, Maryland, is capable of producing up to 2,500 doses of RGX-202 annually, ensuring readiness for market needs upon approval [8][24]. Q&A Session Summary Question: Timing for the Hunter BLA - Management indicated that the BLA acceptance is imminent and they feel confident about the review process [30]. Question: Changes in Approvals and Biomarker Expectations - Management stated that they are prepared for an AdCom if required and are confident in their data supporting the accelerated approval pathway [32][82]. Question: Safety Profile Expectations - Management noted that they do not anticipate changes in the FDA's requirements regarding safety profiles and that enrollment for the pivotal study is on track [38][40]. Question: Updates on Diabetic Retinopathy Phase III Trial - Management confirmed that they are actively working with AbbVie on the final feedback for the trial and expect to begin site activation soon [51]. Question: Functional Data Updates for DMD - Management plans to release additional functional data for RGX-202 in the first half of the year, focusing on expanding the patient data set [57][84]. Question: Impact of Recent Pricing Announcements - Management believes it is too early to assess the impact of recent pricing discussions on their gene therapies [102].