[Executive Summary & Company Overview](index=1&type=section&id=Executive%20Summary%20%26%20Company%20Overview) [CEO Statement & Q2 2025 Highlights](index=1&type=section&id=CEO%20Statement%20%26%20Q2%202025%20Highlights) REGENXBIO's CEO, Curran M. Simpson, highlighted the acceleration of multiple first or best-in-class gene therapy programs in Q2 2025, including the potential FDA approval of clemidsogene lanparvovec (RGX-121) in November, rapid progress of RGX-202, and the advancement of a late-stage program for diabetic retinopathy - REGENXBIO is accelerating multiple first or best-in-class gene therapies for serious diseases like Duchenne, Hunter syndrome, and retinal diseases[3](index=3&type=chunk) - Potential FDA approval of clemidsogene lanparvovec (RGX-121) is on track for **November 2025**[3](index=3&type=chunk) - RGX-202 is progressing rapidly through pivotal study, and a new late-stage program for diabetic retinopathy is advancing[3](index=3&type=chunk) [About REGENXBIO Inc.](index=4&type=section&id=About%20REGENXBIO%20Inc.) REGENXBIO is a biotechnology company focused on AAV gene therapy, advancing a late-stage pipeline for rare and retinal diseases, including RGX-202 for Duchenne, RGX-121 for MPS II, RGX-111 for MPS I (with Nippon Shinyaku), and surabgene lomparvovec (sura-vec) for wet AMD and diabetic retinopathy (with AbbVie), with their AAV platform utilized in treatments for thousands of patients, including Novartis' ZOLGENSMA® - REGENXBIO is a biotechnology company pioneering AAV gene therapy since its founding in **2009**[23](index=23&type=chunk) - The company is advancing a late-stage pipeline of one-time treatments for rare and retinal diseases, including RGX-202, RGX-121, RGX-111, and surabgene lomparvovec[23](index=23&type=chunk) - Thousands of patients have been treated with REGENXBIO's AAV platform, including those receiving Novartis' ZOLGENSMA®[23](index=23&type=chunk) [Program Highlights and Milestones](index=1&type=section&id=PROGRAM%20HIGHLIGHTS%20AND%20MILESTONES) [Neuromuscular Disease Programs](index=1&type=section&id=Neuromuscular%20Disease%20Programs) REGENXBIO is making significant progress in its neuromuscular disease pipeline, with RGX-202 for Duchenne muscular dystrophy on track for accelerated pivotal trial enrollment and BLA submission, and clemidsogene lanparvovec (RGX-121) for MPS II nearing potential FDA approval following successful inspections [RGX-202 for Duchenne Muscular Dystrophy](index=1&type=section&id=RGX-202%20in%20Duchenne%20muscular%20dystrophy) RGX-202, a potential best-in-class gene therapy for Duchenne, is on track for topline results in 1H 2026 and BLA submission mid-2026, with pivotal trial enrollment accelerating and expected to complete in October 2025, ahead of previous guidance, and positive Phase I/II data demonstrating a favorable safety profile and robust microdystrophin expression - RGX-202 pivotal trial enrollment is expected to complete in **October 2025**, ahead of previous guidance[5](index=5&type=chunk)[6](index=6&type=chunk) - Topline results for RGX-202 are expected in the **first half of 2026**, with a Biologics License Application (BLA) submission planned for **mid-2026** under the accelerated approval pathway[5](index=5&type=chunk)[10](index=10&type=chunk) - Phase I/II data showed a favorable safety profile with no serious adverse events or signs of liver injury, and all dose level 2 participants exceeded external natural history controls on functional measures[10](index=10&type=chunk) [Clemidsogene lanparvovec (RGX-121) for MPS II (Hunter Syndrome)](index=1&type=section&id=Clemidsogene%20lanparvovec%20(RGX-121)%20for%20MPS%20II%20(Hunter%20Syndrome)) Clemidsogene lanparvovec (RGX-121) is on track to be the first gene therapy and one-time treatment for MPS II, with an FDA Prescription Drug User Fee Act (PDUFA) target action date of November 9, 2025, following successful FDA inspections of manufacturing, quality systems, and clinical data practices with no observations, and potential FDA approval could result in a Priority Review Voucher (PRV) - RGX-121 is on track for potential FDA approval as the first gene therapy for MPS II, with a PDUFA target action date of **November 9, 2025**[5](index=5&type=chunk)[10](index=10&type=chunk) - FDA Pre-license inspection (PLI) of the in-house manufacturing facility and Bioresearch monitoring information (BIMO) inspection of laboratory and clinical data practices were successfully completed with no observations[5](index=5&type=chunk)[10](index=10&type=chunk) - FDA approval could result in the receipt of a Priority Review Voucher (PRV), to which REGENXBIO has full rights[10](index=10&type=chunk) [Retinal Disease Programs](index=1&type=section&id=Retinal%20Disease%20Programs) REGENXBIO's surabgene lomparvovec (sura-vec) program for retinal diseases is advancing, with positive Phase II data supporting a pivotal program for diabetic retinopathy (DR) via suprachoroidal delivery, and ongoing pivotal trials for wet age-related macular degeneration (wet AMD) via subretinal delivery, with topline results expected in 2026 [Surabgene lomparvovec (sura-vec) for Diabetic Retinopathy (Suprachoroidal Delivery)](index=1&type=section&id=Sura-vec%20for%20the%20Treatment%20of%20DR%20(Suprachoroidal%20Delivery)) Sura-vec for diabetic retinopathy (DR) is advancing to a global pivotal program, supported by positive Phase II ALTITUDE® trial data reported in June 2025, demonstrating a durable safety and efficacy profile through two years with a single, in-office injection and no drug-related serious adverse events, with a two-part placebo-controlled Phase IIb/III trial to be initiated with 2-step DRSS improvement as the primary endpoint - Sura-vec using suprachoroidal delivery for diabetic retinopathy is advancing to a global pivotal program, supported by positive Phase II trial data[5](index=5&type=chunk)[10](index=10&type=chunk) - Phase II ALTITUDE® trial data demonstrated durable safety and efficacy in patients with non-proliferative DR through **two years** with a single, in-office injection, with no drug-related serious adverse events[10](index=10&type=chunk) - A two-part placebo-controlled Phase IIb/III trial will be initiated, with the primary endpoint being **2-step DRSS improvement**[10](index=10&type=chunk) [Surabgene lomparvovec (sura-vec) for Wet AMD (Subretinal Delivery)](index=1&type=section&id=Sura-vec%20for%20the%20Treatment%20of%20Wet%20AMD%20(Subretinal%20Delivery)) Enrollment is ongoing in the ATMOSPHERE® and ASCENT™ pivotal trials for the subretinal delivery of sura-vec in patients with wet AMD, with topline results expected in 2026, positioning sura-vec to be the first approved gene therapy for wet AMD - Enrollment is ongoing in the ATMOSPHERE® and ASCENT™ pivotal trials for subretinal delivery of sura-vec in patients with wet AMD[11](index=11&type=chunk) - Topline results for subretinal sura-vec in wet AMD are expected in **2026**[5](index=5&type=chunk)[11](index=11&type=chunk) - Sura-vec is on track to be the first approved gene therapy for wet AMD[5](index=5&type=chunk)[11](index=11&type=chunk) [Surabgene lomparvovec (sura-vec) for Wet AMD (Suprachoroidal Delivery)](index=3&type=section&id=Sura-vec%20for%20the%20Treatment%20of%20Wet%20AMD%20(Suprachoroidal%20Delivery)) The Phase II AAVIATE® trial continues enrolling a new cohort to evaluate sura-vec at dose level 4 (1.5x10e12 GC/eye) for wet AMD using suprachoroidal delivery, with patients in this cohort also receiving short-course prophylactic steroid eye drops - The Phase II AAVIATE® trial is enrolling a new cohort to evaluate suprachoroidal sura-vec at **dose level 4 (1.5x10e12 GC/eye)** for wet AMD[12](index=12&type=chunk) - Patients in this cohort will receive short-course prophylactic steroid eye drops[12](index=12&type=chunk) [Corporate Updates](index=3&type=section&id=CORPORATE%20UPDATES) [Royalty Monetization](index=3&type=section&id=Royalty%20Monetization) In May 2025, REGENXBIO closed a non-dilutive, limited recourse royalty bond agreement of up to $250 million with Healthcare Royalty (HCRx), receiving $150 million at closing and eligible for an additional $100 million in two separate $50 million tranches - Closed a non-dilutive, limited recourse royalty bond agreement of up to **$250 million** with Healthcare Royalty (HCRx) in **May 2025**[13](index=13&type=chunk) - Received **$150 million** at closing and is eligible for an additional **$100 million** in two **$50 million** tranches[13](index=13&type=chunk) [AbbVie Eye Care Collaboration Amendment](index=3&type=section&id=AbbVie%20Eye%20Care%20Collaboration) In August 2025, REGENXBIO and AbbVie amended their collaboration and license agreement, updating the milestone structure for the diabetic retinopathy (DR) program, with AbbVie paying REGENXBIO $100 million upon the first subject dosed in the Phase IIb/III trial and an additional $100 million for a second Phase III clinical trial, and AbbVie independently advancing and funding a new Phase III ACHIEVE trial for wet AMD - Amendment to the collaboration and license agreement with AbbVie includes an updated milestone structure for the DR program[17](index=17&type=chunk) - AbbVie will pay REGENXBIO **$100 million** upon first subject dosed in the Phase IIb/III trial and an additional **$100 million** upon first subject dosed in a second Phase III clinical trial[17](index=17&type=chunk) - AbbVie will independently advance and pay all costs for a new Phase III ACHIEVE trial in wet AMD[17](index=17&type=chunk) [Financial Results (Q2 2025)](index=3&type=section&id=FINANCIAL%20RESULTS) [Cash Position](index=3&type=section&id=Cash%20Position) REGENXBIO's cash, cash equivalents, and marketable securities increased to $363.6 million as of June 30, 2025, from $244.9 million at December 31, 2024, primarily driven by a $110.0 million upfront payment from the Nippon Shinyaku partnership and $144.5 million in net proceeds from the HCRx royalty monetization, partially offset by cash used in operating activities Cash, Cash Equivalents and Marketable Securities | Metric | June 30, 2025 (in millions) | December 31, 2024 (in millions) | Change | | :-------------------------------- | :-------------------------- | :-------------------------- | :----- | | Cash, cash equivalents & marketable securities | $363.6 | $244.9 | +$118.7 | - The increase was primarily attributable to a **$110.0 million** upfront payment from the Nippon Shinyaku partnership (March 2025) and **$144.5 million** in net proceeds from the royalty monetization with HCRx (May 2025)[15](index=15&type=chunk) [Revenues](index=3&type=section&id=Revenues) Total revenues for the three months ended June 30, 2025, decreased slightly to $21.4 million from $22.3 million in the prior year period, primarily due to lower Zolgensma royalties, partially offset by an increase in service revenues, mainly from the Nippon Shinyaku partnership Revenues (Three Months Ended June 30) | Revenue Type | Q2 2025 (in thousands) | Q2 2024 (in thousands) | YoY Change (in thousands) | YoY Change (%) | | :------------------------ | :--------------------- | :--------------------- | :------------------------ | :------------- | | License and royalty revenue | $18,465 | $21,846 | $(3,381) | -15.5% | | Service revenue | $2,894 | $449 | $2,445 | +544.5% | | **Total revenues** | **$21,359** | **$22,295** | **$(936)** | **-4.2%** | - The decrease in total revenues was primarily attributable to Zolgensma royalties, which decreased from **$21.8 million** in Q2 2024 to **$18.4 million** in Q2 2025[16](index=16&type=chunk) - The decrease was partially offset by an increase in service revenues, driven primarily by **$2.7 million** of development service revenue under the Nippon Shinyaku partnership in Q2 2025[16](index=16&type=chunk) [Operating Expenses](index=3&type=section&id=Operating%20Expenses) Operating expenses increased to $84.6 million in Q2 2025 from $78.3 million in Q2 2024, primarily driven by higher research and development expenses related to pivotal trials and increased general and administrative costs [Research and Development Expenses](index=3&type=section&id=Research%20and%20Development%20Expenses) Research and development expenses increased to $59.5 million for Q2 2025, up from $48.9 million for Q2 2024, primarily due to higher manufacturing-related expenses, other clinical supply costs, and clinical trial expenses for the sura-vec and RGX-202 pivotal trials Research and Development Expenses (Three Months Ended June 30) | Metric | Q2 2025 (in thousands) | Q2 2024 (in thousands) | YoY Change (in thousands) | YoY Change (%) | | :------------------------ | :--------------------- | :--------------------- | :------------------------ | :------------- | | Research and development | $59,500 | $48,869 | $10,631 | +21.8% | - The increase was primarily attributable to manufacturing-related expenses and other clinical supply costs and clinical trial expenses for sura-vec and RGX-202 pivotal trials[18](index=18&type=chunk) [General and Administrative Expenses](index=4&type=section&id=General%20and%20Administrative%20Expenses) General and administrative expenses increased slightly to $19.9 million for Q2 2025, compared to $18.9 million for Q2 2024, mainly due to increased personnel-related costs and expenses for consulting and professional services General and Administrative Expenses (Three Months Ended June 30) | Metric | Q2 2025 (in thousands) | Q2 2024 (in thousands) | YoY Change (in thousands) | YoY Change (%) | | :-------------------------- | :--------------------- | :--------------------- | :------------------------ | :------------- | | General and administrative | $19,883 | $18,855 | $1,028 | +5.5% | - The increase was primarily attributable to personnel-related costs and expenses for consulting and professional services[19](index=19&type=chunk) [Net Loss](index=4&type=section&id=Net%20Loss) REGENXBIO reported a net loss of $70.9 million, or $1.38 basic and diluted net loss per share, for Q2 2025, widening from a net loss of $53.0 million, or $1.05 per share, in Q2 2024, primarily driven by higher operating expenses and a significant increase in interest expense Net Loss (Three Months Ended June 30) | Metric | Q2 2025 (in thousands) | Q2 2024 (in thousands) | YoY Change (in thousands) | YoY Change (%) | | :------------------------ | :--------------------- | :--------------------- | :------------------------ | :------------- | | Net loss | $(70,871) | $(52,989) | $(17,882) | +33.7% | | Net loss per share (basic & diluted) | $(1.38) | $(1.05) | $(0.33) | +31.4% | - The increase in net loss was influenced by higher research and development expenses and a significant increase in interest expense[18](index=18&type=chunk)[20](index=20&type=chunk)[30](index=30&type=chunk) [Financial Guidance](index=4&type=section&id=FINANCIAL%20GUIDANCE) [Cash Runway Guidance](index=4&type=section&id=Cash%20Runway%20Guidance) REGENXBIO expects its balance of cash, cash equivalents, and marketable securities, totaling $363.6 million as of June 30, 2025, to fund its operations into early 2027, with this guidance based on current operational plans and excluding the impact of potential material payments from partners or licensees, as well as the potential monetization of a Priority Review Voucher (PRV) - Cash, cash equivalents, and marketable securities of **$363.6 million** as of **June 30, 2025**, are expected to fund operations into **early 2027**[21](index=21&type=chunk) - This cash runway guidance excludes the impact of any material payments from partners or licensees and potential monetization of a PRV[21](index=21&type=chunk) [Financial Statements](index=6&type=section&id=Financial%20Statements) [Consolidated Balance Sheets](index=6&type=section&id=Consolidated%20Balance%20Sheets) As of June 30, 2025, REGENXBIO's total assets increased to $581.0 million from $466.0 million at December 31, 2024, while total liabilities significantly increased to $367.3 million from $206.3 million, primarily driven by a substantial rise in royalty monetization liabilities and deferred revenue, consequently decreasing total stockholders' equity to $213.7 million from $259.7 million Consolidated Balance Sheet Highlights (in thousands) | Metric | June 30, 2025 | December 31, 2024 | Change | | :------------------------- | :-------------- | :---------------- | :----- | | Total assets | $581,027 | $465,989 | +$115,038 | | Total liabilities | $367,348 | $206,338 | +$161,010 | | Total stockholders' equity | $213,679 | $259,651 | $(45,972) | - Royalty monetization liabilities increased significantly from **$25,378 thousand** at December 31, 2024, to **$153,693 thousand** at June 30, 2025[29](index=29&type=chunk) - Deferred revenue (non-current) increased from **$0** to **$23,804 thousand**[29](index=29&type=chunk) [Consolidated Statements of Operations and Comprehensive Loss](index=7&type=section&id=Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For the six months ended June 30, 2025, total revenues significantly increased to $110.4 million from $37.9 million in the prior year period, primarily due to a substantial rise in license and royalty revenue, and despite an increase in total operating expenses, the loss from operations improved, leading to a net loss of $64.8 million, a reduction from the $116.3 million net loss in the same period of 2024, though interest expense also saw a notable increase Consolidated Statements of Operations Highlights (Six Months Ended June 30, in thousands) | Metric | 6 Months Ended June 30, 2025 | 6 Months Ended June 30, 2024 | YoY Change (in thousands) | YoY Change (%) | | :-------------------------------- | :--------------------------- | :--------------------------- | :------------------------ | :------------- | | Total revenues | $110,371 | $37,917 | $72,454 | +191.1% | | Total operating expenses | $161,522 | $157,817 | $3,705 | +2.3% | | Loss from operations | $(51,151) | $(119,900) | $68,749 | -57.3% | | Total other income (expense) | $(13,637) | $3,581 | $(17,218) | -480.8% | | Net loss | $(64,788) | $(116,319) | $51,531 | -44.3% | | Net loss per share (basic & diluted) | $(1.26) | $(2.41) | $(1.15) | -47.7% | - The substantial increase in total revenues for the six-month period was primarily driven by license and royalty revenue, which rose from **$37,190 thousand** to **$105,514 thousand**[30](index=30&type=chunk) - Interest expense significantly increased from **$2,422 thousand** in the first six months of 2024 to **$19,563 thousand** in the same period of 2025[30](index=30&type=chunk) [Additional Information](index=4&type=section&id=Additional%20Information) [Conference Call Details](index=4&type=section&id=CONFERENCE%20CALL) REGENXBIO hosted a conference call and webcast on August 7, 2025, at 8:00 a.m. ET to discuss the second quarter 2025 financial results and operational highlights, with details for webcast registration and dial-in for the Q&A session provided - REGENXBIO hosted a conference call and webcast at **8:00 a.m. ET** on **August 7, 2025**[5](index=5&type=chunk)[22](index=22&type=chunk) - Listeners could register for the webcast via a provided link, and analysts could access the live call by dialing specific numbers and entering a passcode[22](index=22&type=chunk) [Forward-Looking Statements](index=4&type=section&id=FORWARD-LOOKING%20STATEMENTS) This press release contains forward-looking statements regarding REGENXBIO's future operations, clinical trials, costs, and cash flow, based on current expectations and assumptions, which are subject to various risks and uncertainties, including the timing and success of clinical trials, regulatory approvals, and market acceptance, as detailed in the company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the SEC - The press release includes forward-looking statements concerning REGENXBIO's future operations, clinical trials, costs, and cash flow[24](index=24&type=chunk)[25](index=25&type=chunk) - These statements are subject to a number of risks and uncertainties, including the timing of enrollment, commencement and completion and the success of clinical trials, regulatory approval, and market acceptance[25](index=25&type=chunk) - Readers are cautioned not to rely too heavily on these statements, and REGENXBIO does not undertake any obligation to update or revise them, except as required by law[25](index=25&type=chunk) [Contacts](index=5&type=section&id=CONTACTS) Contact information for REGENXBIO's Corporate Communications (Dana Cormack) and Investor Relations (George E. MacDougall) is provided for inquiries - Contact information for Corporate Communications (Dana Cormack) and Investor Relations (George E. MacDougall) is provided[27](index=27&type=chunk)

Core Insights - REGENXBIO Inc. reported strong operational momentum in advancing its gene therapy programs, particularly with RGX-121 and RGX-202, aimed at treating serious diseases such as Duchenne muscular dystrophy and Hunter syndrome [2][4][5] Financial Results - Cash, cash equivalents, and marketable securities increased to $363.6 million as of June 30, 2025, from $244.9 million at the end of 2024, primarily due to a $110 million upfront payment from Nippon Shinyaku and $144.5 million from royalty monetization [16][21] - Revenues for the second quarter of 2025 were $21.4 million, a slight decrease from $22.3 million in the same period of 2024, mainly due to a drop in Zolgensma royalties [17] - Research and development expenses rose to $59.5 million in Q2 2025 from $48.9 million in Q2 2024, driven by manufacturing and clinical trial costs [18] - General and administrative expenses increased to $19.9 million in Q2 2025 from $18.9 million in Q2 2024, attributed to personnel and consulting costs [19] - The net loss for Q2 2025 was $70.9 million, compared to a net loss of $53.0 million in Q2 2024, reflecting increased operational costs [20] Program Highlights - RGX-202 is positioned as a potential best-in-class gene therapy for Duchenne muscular dystrophy, with pivotal trial enrollment expected to complete by October 2025 [3][5] - Clemidsogene lanparvovec (RGX-121) is on track for potential FDA approval in November 2025, with successful completion of FDA inspections [4][13] - Surabgene lomparvovec (sura-vec) is advancing towards pivotal trials for diabetic retinopathy and wet AMD, with topline results expected in 2026 [7][9] Corporate Updates - In May 2025, REGENXBIO closed a $250 million royalty bond agreement, receiving $150 million upfront [11] - An amendment to the collaboration agreement with AbbVie was executed in August 2025, which includes milestone payments for the diabetic retinopathy program [14] Financial Guidance - The company expects its cash position to fund operations into early 2027, excluding potential payments from partners or monetization of a Priority Review Voucher [21]

Company Overview - REGENXBIO Inc. is a biotechnology company focused on gene therapy with a mission to improve lives through its curative potential [3] - The company has been a pioneer in AAV gene therapy since its founding in 2009 [3] - REGENXBIO is advancing a late-stage pipeline of one-time treatments for rare and retinal diseases, including RGX-202 for Duchenne, RGX-121 for MPS II, and RGX-111 for MPS I, in partnership with Nippon Shinyaku [3] - The company is also collaborating with AbbVie on surabgene lomparvovec (ABBV-RGX-314) for wet AMD and diabetic retinopathy [3] - Thousands of patients have been treated with REGENXBIO's AAV platform, including those receiving Novartis' ZOLGENSMA® [3] Upcoming Events - REGENXBIO will host a conference call on August 7, 2025, at 8:00 a.m. ET to discuss its financial results for Q2 2025 and operational highlights [1] - Listeners can register for the webcast and analysts can participate in the Q&A session by dialing specific numbers [2] - A replay of the webcast will be available on the company's investor website approximately two hours after the call [2]

Core Insights - REGENXBIO Inc. announced preclinical results showing that a microdystrophin gene therapy construct with the C-terminal (CT) domain provides improved functional benefits for patients with Duchenne Muscular Dystrophy compared to a construct without the CT domain [1][4][5] - RGX-202 is the only investigational microdystrophin gene therapy candidate that includes the CT domain, making it closest to naturally occurring dystrophin [2][8] Group 1: Research Findings - The preclinical study published in Molecular Therapy Methods and Clinical Development demonstrated that the microdystrophin with the CT domain was maintained at higher levels in transduced muscles and effectively recruited the dystrophin-associated protein complex to the muscle membrane [4][5] - The incorporation of the CT domain enhances the microdystrophin design, allowing for higher accumulation levels in muscle and potentially improving functional benefits [5][7] Group 2: Clinical Trial Insights - Interim results from the Phase I/II AFFINITY DUCHENNE trial indicated that RGX-202 showed consistent evidence of positively changing the disease trajectory in patients with Duchenne and had a favorable safety profile [5][6] - REGENXBIO is currently enrolling participants in the pivotal portion of the Phase I/II/III AFFINITY DUCHENNE trial and plans to submit a Biologics License Application (BLA) via the accelerated approval pathway in mid-2026 [6][9] Group 3: Company Overview - REGENXBIO is a biotechnology company focused on gene therapy, with a late-stage pipeline that includes RGX-202 for Duchenne, among other treatments for rare diseases [11] - The company has pioneered AAV gene therapy since its founding in 2009 and has treated thousands of patients with its AAV platform [11]

Company Overview - Regenxbio is a clinical-stage biopharmaceutical company that specializes in gene therapies, founded in 2008 [1] - The company's core technology involves the delivery of rescue genes using AAV (adeno-associated virus) payloads, which is increasingly being utilized in approved drugs [1] Industry Insights - The healthcare sector is complex, and financial professionals and investors require scientific and clinical expertise to navigate it effectively [1] - There is a growing emphasis on bridging the gap between advanced scientific research and financial strategy to uncover hidden value and assess risks accurately in life sciences [1]

Core Insights - RegenXBio Inc. has released new interim data from the Phase 1/2 AFFINITY DUCHENNE trial, showcasing positive functional, safety, and biomarker data for RGX-202, a gene therapy for Duchenne muscular dystrophy [1][2]. Group 1: Trial Data and Results - The trial involved five patients aged six to twelve years who received RGX-202, demonstrating consistent benefits in functional data among dose level 2 participants at 9 and 12 months post-treatment [1]. - At 9 months, RGX-202 participants showed improved function, exceeding external controls on all measures, with an average improvement of 4 points on the North Star Ambulatory Assessment (NSAA) from baseline and 4.8 points compared to natural history [3]. - At 12 months, RGX-202 participants continued to demonstrate improved performance on timed function tests and NSAA, with an average improvement of 4.5 points from baseline and 6.8 points compared to natural history [4]. Group 2: Future Plans and Market Context - RegenXBio plans to share topline data for RGX-202 in the first half of 2026 and aims to submit a Biologics License Application (BLA) under the accelerated approval pathway by mid-2026, with commercial readiness activities underway for a potential launch in 2027 [5]. - The competitive landscape includes Sarepta Therapeutics, which recently reported a patient death following treatment with its approved gene therapy Elevidys, leading to a therapeutic clinical hold on several studies in the EU [6].

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.